epoetin-alfa and Anemia

Anemia persists as a challenge in chronic kidney disease (CKD) patients. Current therapies are the injectable erythropoietin stimulating agents (ESA). Concerns have been raised regarding ESA cardiovascular safety, therefore search for an alternative, convenient and safe therapy is underway. Hypoxia inducible factors-prolyl hydroxylase inhibitors (HIF-PHI) are oral agents with promising results. Numerous small studies reported favorable effects with lack of large, powered studies.. We conducted a meta-analysis of randomized clinical trials to assess the efficacy and safety of HIF-PHI in non-dialysis-dependent CKD patients. Primary outcome was hemoglobin (Hb) concentration post intervention. Secondary outcomes were all-cause mortality, MACE, and changes in iron metabolism (ferritin, hepcidin). We reported total and serious adverse effects. Data were pooled using a random effect model via RevMan 5.4 software.. We identified 7 trials comprising of 8228 patients (mean age 66.5 ± 13.2 years, 42% were females, 53% used iron replacement) with a mean follow-up of 52 weeks. Compared with the standard of care (ESA), HIF-PHI were non-inferior for treatment of anemia, with comparable effect on mortality and major adverse cardiovascular events. HIF-PHI showed no major safety concerns. Main side effect of HIF-PHI was diarrhea.. HIF-PHI might represent a safe, and convenient alternative to ESA in non-dialysis dependent CKD patients with anemia.

Topics: Aged; Anemia; Epoetin Alfa; Female; Humans; Hypoxia; Iron; Male; Middle Aged; Prolyl Hydroxylases; Prolyl-Hydroxylase Inhibitors; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic

Biosimilars offer the potential to expand patient access and reduce healthcare costs. Therefore, it is of importance that clinicians and patients are reassured about their efficacy and safety in practice. In 2007, Binocrit® (HX575; Sandoz GmbH, Kundl, Austria) was the first epoetin alfa biosimilar approved for use in chemotherapy induced anaemia (CIA), chronic renal failure (CRF), and more recently myelodysplastic (MDS) anaemia. Since its approval, there has been a plethora of data demonstrating the well-tolerated safety profile of HX575. This review will outline the safety results collected from key studies that have added to the extensive HX575 (Binocrit® unless otherwise stated) clinical experience. With a focus on all approved indications, we will review the safety data collected across a range of study types, to further consolidate the reassurance for the use of HX575 in these indications.

Topics: Anemia; Biosimilar Pharmaceuticals; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins; Therapeutic Equivalency

Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anaemia in people with chronic kidney disease (CKD). However, their use has been associated with cardiovascular events. This is an update of a Cochrane review first published in 2014.. To compare the efficacy and safety of ESAs (epoetin alfa, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, and biosimilar ESAs against each other, placebo, or no treatment) to treat anaemia in adults with CKD.. In this update, we searched the Cochrane Kidney and Transplant Register of Studies up to 29 April 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.. Randomised controlled trials (RCTs) that included a comparison of an ESA (epoetin alfa, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, a biosimilar epoetin or a biosimilar darbepoetin alfa) with another ESA, placebo or no treatment in adults with CKD were considered for inclusion.. Two independent authors screened the search results and extracted data. Data synthesis was performed using random-effects pairwise meta-analysis (expressed as odds ratios (OR) and their 95% confidence intervals (CI)) and network meta-analysis. We assessed for heterogeneity and inconsistency within meta-analyses using standard techniques and planned subgroup and meta-regression to explore sources of heterogeneity or inconsistency. We assessed certainty in treatment estimates for the primary outcomes (preventing blood transfusions and death (any cause)) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.. Sixty-two new studies (9237 participants) were included in this update, so the review now includes 117 studies with 25,237 participants. Most studies were at high or unclear risk of bias in most methodological domains. Overall, results remain similar in this update compared to our previous review in 2014. For preventing blood transfusion, epoetin alfa (OR 0.28, 95% CI 0.13 to 0.61; low certainty evidence) and epoetin beta (OR 0.19, 95% CI 0.08 to 0.47; low certainty evidence) may be superior to placebo, and darbepoetin alfa was probably superior to placebo (OR 0.27, 95% CI 0.11 to 0.67; moderate certainty evidence). Methoxy polyethylene glycol-epoetin beta (OR 0.33, 95% CI 0.11 to 1.02; very low certainty evidence), a biosimilar epoetin (OR 0.34, 95% CI 0.11 to 1.03; very low certainty evidence) and a biosimilar darbepoetin alfa (OR 0.37, 95% CI 0.07 to 1.91; very low certainty evidence) had uncertain effects on preventing blood transfusion compared to placebo. The comparative effects of ESAs compared with another ESA on preventing blood transfusions were uncertain, in low to very low certainty evidence. Effects on death (any cause) were uncertain for epoetin alfa (OR 0.79, 95% CI 0.51 to 1.22; low certainty evidence), epoetin beta (OR 0.69, 95% CI 0.40 to 1.20; low certainty evidence), methoxy polyethylene glycol-epoetin beta (OR 1.07, 95% CI 0.67 to 1.71; very low certainty evidence), a biosimilar epoetin (OR 0.80, 95% CI 0.47 to 1.36; low certainty evidence) and a biosimilar darbepoetin alfa (OR 1.63, 95% CI 0.51 to 5.23; very low certainty evidence) compared to placebo. There was probably no difference between darbepoetin alfa and placebo on the odds of death (any cause) (OR 0.99, 95% CI 0.81 to 1.21; moderate certainty evidence). The comparative effects of ESAs compared with another ESA on death (any cause) were uncertain in low to very low certainty evidence. Epoetin beta probably increased the odds of hypertension when compared to placebo (OR 2.17, 95% CI 1.17 to 4.00; moderate certainty evidence). Compared to placebo, epoetin alfa (OR 2.10, 95% CI 1.22 to 3.59; very low certainty evidence), darbepoetin alfa (OR 1.88, 95% CI 1.12 to 3.14; low certainty evidence) and methoxy polyethylene glycol-epoetin beta (OR 1.98, 95% CI 1.05 to 3.74; low certainty evidence) may increase the odds of hypertension, but a biosimilar epoetin (OR 1.88, 95% CI 0.96 to 3.67; low certainty evidence) and biosimilar darbepoetin alfa (OR 1.98, 95% CI 0.84 to 4.66; low certa. Los fármacos estimulantes de la eritropoyesis (FEE) se suelen utilizar para tratar la anemia en personas con nefropatía crónica. Sin embargo, su uso se ha asociado a eventos cardiovasculares. Esta es una actualización de una revisión Cochrane publicada por primera vez en 2014.. Comparar la eficacia y la seguridad de los FEE (epoetina alfa, epoetina beta, darbepoetina alfa o metoxi‐polietilenglicol epoetina beta y FEE biosimilares) entre sí, con placebo, o ningún tratamiento, para el tratamiento de la anemia en adultos con nefropatía crónica. MÉTODOS DE BÚSQUEDA: En esta actualización, a través del contacto con el documentalista, y con el uso de términos de búsqueda pertinentes para esta revisión, se realizaron búsquedas en el Registro de estudios del Grupo Cochrane de Riñón y trasplante (Cochrane Kidney and Transplant) hasta el 29 de abril de 2022. Los estudios en el registro se identifican mediante búsquedas en CENTRAL, MEDLINE y EMBASE, en resúmenes de congresos, en el portal de búsqueda de la Plataforma de registros internacionales de ensayos clínicos (ICTRP) y en ClinicalTrials.gov. CRITERIOS DE SELECCIÓN: Se consideraron para la inclusión los ensayos controlados aleatorizados (ECA) que incluían una comparación de un FEE (epoetina alfa, epoetina beta, darbepoetina alfa o metoxi‐polietilenglicol epoetina beta, una epoetina biosimilar o una darbepoetina alfa biosimilar) con otro FEE, placebo o ningún tratamiento en adultos con NC. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores independientes examinaron los resultados de la búsqueda y extrajeron los datos. La síntesis de los datos se realizó mediante un metanálisis pareado de efectos aleatorios (expresada como odds ratio [OR] y sus intervalos de confianza [IC] del 95%) y un metanálisis en red. Se evaluó la heterogeneidad y la inconsistencia dentro de los metanálisis con técnicas estándares y se planeó crear subgrupos y una metarregresión para explorar las fuentes de heterogeneidad o la inconsistencia. Se evaluó la certeza en las estimaciones del tratamiento para los desenlaces principales (prevención de transfusiones de sangre y muerte [por cualquier causa]) mediante el método Grading of Recommendations Assessment, Development and Evaluation (GRADE).. En esta actualización se incluyeron 62 nuevos estudios (9237 participantes), por lo que la revisión incluye ahora 117 estudios con 25 237 participantes. La mayoría de los estudios tuvieron riesgo alto o incierto de sesgo en la mayoría de los dominios metodológicos. En general, los resultados siguen siendo similares en esta actualización en comparación con la revisión anterior de 2014. Para prevenir la transfusión de sangre, la epoetina alfa (OR 0,28; IC del 95%: 0,13 a 0,61; evidencia de certeza baja) y la epoetina beta (OR 0,19; IC del 95%: 0,08 a 0,47; evidencia de certeza baja) podrían ser superiores al placebo, y la darbepoetina alfa fue probablemente superior al placebo (OR 0,27; IC del 95%: 0,11 a 0,67; evidencia de certeza moderada). La metoxi‐polietilenglicol epoetina beta (OR 0,33; IC del 95%: 0,11 a 1,02; evidencia de certeza muy baja), una epoetina biosimilar (OR 0,34; IC del 95%: 0,11 a 1,03; evidencia de certeza muy baja) y una darbepoetina alfa biosimilar (OR 0,37; IC del 95%: 0,07 a 1,91; evidencia de certeza muy baja) tuvieron efectos inciertos sobre la prevención de la transfusión de sangre en comparación con el placebo. Los efectos comparativos de los FEE comparados con otro FEE sobre la prevención de las transfusiones de sangre fueron inciertos, en evidencia de certeza baja a muy baja. Los efectos sobre la mortalidad (por cualquier causa) fueron inciertos para la epoetina alfa (OR 0,79; IC del 95%: 0,51 a 1,22; evidencia de certeza baja), la epoetina beta (OR 0,69; IC del 95%: 0,40 a 1,20; evidencia de certeza baja), la metoxi‐polietilenglicol epoetina beta (OR 1,07; IC del 95%: 0,67 a 1,71; evidencia de certeza muy baja), una epoetina biosimilar (OR 0,80; IC del 95%: 0,47 a 1,36; evidencia de certeza baja) y una darbepoetina alfa biosimilar (OR 1,63; IC del 95%: 0,51 a 5,23; evidencia de certeza muy baja) en comparación con el placebo. Es probable que no hubiera diferencias entre la darbepoetina alfa y el placebo en las probabilidades de muerte (por cualquier causa) (OR 0,99; IC del 95%: 0,81 a 1,21; evidencia de certeza moderada). Los efectos comparativos de los FEE comparados con otro FEE sobre la mortalidad (por cualquier causa) fueron inciertos en evidencia de certeza baja a muy baja. Es probable que la epoetina beta aumentara el riesgo de hipertensión en comparación con el placebo (OR 2,17; IC del 95%: 1,17 a 4,00; evidencia de certeza moderada). En comparación con el placebo, la epoetina alfa (OR 2,10; IC del 95%: 1,22 a 3,59; ev. Los efectos comparativos de los diferentes FEE sobre las transfusiones de sangre, la mortalidad (por cualquier causa y cardiovascular), los eventos cardiovasculares mayores, el infarto de miocardio, el accidente cerebrovascular, la trombosis de acceso vascular, la insuficiencia renal, el cansancio y la disnea fueron inciertos.

Topics: Adult; Anemia; Biosimilar Pharmaceuticals; Darbepoetin alfa; Dyspnea; Epoetin Alfa; Erythropoiesis; Hematinics; Humans; Hypertension; Myocardial Infarction; Network Meta-Analysis; Renal Insufficiency, Chronic; Thrombosis

Renal anemia, a common complication and threat factor of chronic kidney disease (CKD), has long been treated with injectable erythropoietin-stimulating agents (ESAs). As concerns regarding cardiovascular safety and erythropoietin resistance to ESAs have emerged, alternative therapies are urgently needed. Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), an oral agent, has been proven to be effective in improving renal anemia. However, the effects of HIF-PHIs on nondialysis-dependent CKD (NDD-CKD) have yet to be supported by updated meta-analyses.. A meta-analysis of clinical randomized controlled trials (RCTs) on HIF-PHI treatment of NDD-CKD patients based on PubMed, EMBASE, and Cochrane databases as of July 16th, 2023, was conducted. The primary outcomes were the level of hemoglobin (Hb) postintervention and the ratio of Hb responses. Most of the analysis was conducted. Twenty-two studies with a total of 7178 subjects in the HIF-PHI group, 3501 subjects in the ESA group and 2533 subjects in the placebo group were enrolled. HIF-PHIs increased the level of Hb and improved iron metabolism but were not inferior to ESAs in terms of safety.. HIF-PHIs may be a convenient and safe alternative to ESAs in patients with NDD-CKD and anemia.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Hypoxia; Prolyl Hydroxylases; Prolyl-Hydroxylase Inhibitors; Renal Insufficiency, Chronic

Erythropoiesis-stimulating agents (ESA) are commonly used in clinical practice to improve anaemia. Despite a number of patients successfully treated without adverse events, the complications have been previously reported.. To report and review the characteristics and management of ESA hypersensitivities.. Case reports and related articles associated with ESA use, published between January 1999 and December 2018, were retrieved through Electronic databases (MEDLINE® and PubMed®).. Forty-seven ESA patients with various immediate and delayed hypersensitivity reactions caused by epoetin and pharmaceutical excipients were identified from nineteen studies and one case report in this paper. Fatal hypersensitivity to ESA and ESA-allergic cross-reactivities have been documented. Desensitization or change of EPO molecular structure has been reported as successful methods of re-introducing the drug.. ESA hypersensitivity in the various allergic reactions and cross-reactivity have been documented. Desensitization and Epoetin structural changes could be successful methods to re-introduce the drug.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Hematinics; Humans; Pruritus; Recombinant Proteins

Topics: Anemia; Biosimilar Pharmaceuticals; Drug Approval; Epoetin Alfa; Hematinics; Humans; Quality of Life; United States

Biosimilars are biologic drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety, and efficacy. Biosimilar epoetin received Food and Drug Administration (FDA) approval in 2018. The manufacturer received an FDA nonapproval letter in 2017, despite receiving a favorable review by FDA's Oncologic Drugs Advisory Committee (ODAC) and an FDA nonapproval letter in 2015 for an earlier formulation. We discuss the 2018 FDA approval, the 2017 FDA ODAC Committee review, and the FDA complete response letters in 2015 and 2017; review concepts of litigation, naming, labeling, substitution, interchangeability, and pharmacovigilance; review European and U.S. oncology experiences with biosimilar epoetin; and review the safety of erythropoiesis-stimulating agents. In 2020, policy statements from AETNA, United Health Care, and Humana indicated that new epoetin oncology starts must be for biosimilar epoetin unless medical need for other epoetins is documented. Empirical studies report that as of 2012, reference epoetin use decreased from 40%-60% of all patients with cancer with chemotherapy-induced anemia to <5% of such patients because of safety concerns. Between 2018 and 2020, biosimilar epoetin use varied, increasing to 81% among one private insurer's patients covered by Medicare whose cancer care is administered with Oncology Analytics and to 41% with the same private insurer's patients with cancer covered by commercial health insurance and administered by the private insurer, to 0% in several Veterans Administration Hospitals, increasing to 100% in one large county hospital in California, and with yet-to-be-reported data from most oncology settings. We conclude that biosimilar epoetin appears to have overcome some barriers since 2015, although current uptake in the U.S. is variable. Pricing and safety considerations for all erythropoiesis-stimulating agents are primary determinants of biosimilar epoetin oncology uptake. IMPLICATIONS FOR PRACTICE: Few oncologists understand substitution and interchangeability of biosimilars with reference drugs. Epoetin biosimilar is new to the market, and physician and patient understanding is limited. The development of epoetin biosimilar is not familiar to oncologists.

Topics: Aged; Anemia; Antineoplastic Agents; Biosimilar Pharmaceuticals; Epoetin Alfa; Humans; Medicare; Neoplasms; United States

Erythropoiesis stimulating agents are exogenous erythropoietin medications that are used to stimulate the bone marrow red blood cells' production for the management of anemia of chronic kidney disease, some anticancer drugs, myelodysplastic syndrome, and others. Currently, there are different erythropoiesis stimulating agents accessible in the market. The objective of this narrative literature review is to summarize the role of some erythropoiesis stimulating agents in the treatment of anemia.. The following method was used to prepare this narrative literature review. The comprehensive computerized search of literatures was carried out using PubMed, Cochrane library, Google scholar, and Science direct. Keywords such as recombinant human erythropoietin, epoetin, darbepoetin, continuous erythropoietin receptor agonist, pegzyrepoetin alfa, erythropoiesis stimulating agents in combination with anemia/anaemia were used. The pertinent original and review full articles which are written in the English language were included in this narrative review.. From the discussions of the literature, erythropoiesis stimulating agents that are produced by different biosimilar manufacturers have different clinical characteristics and stabilities as a result of their chemical modifications. The chemical modifications of erythropoiesis stimulating agents like glycosylation and polyethylene glycosylation determine the half-life, affinity to erythropoietin receptor, and immune response of the agents. Erythro-poiesis stimulating agents are categorized as short-acting and long-acting agents due to their chemical structures that influence the clinical efficacy and safety of the agents.. The effectiveness of the agents is different in different patients depending on the individual characteristics and etiologies of anemia. The agents not only have the benefits but also, they have the risks for the patients. Hence, the risks and benefits of erythropoiesis stimulating agents must be given special consideration in the managements of anemia to get maximum efficacy for anemic patients. The treatment is dependent on hemoglobin levels of individual patients. The physician must follow the patients during and after therapy using erythropoiesis stimulating agents.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Humans; Recombinant Proteins

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of oral medicines being developed for the treatment of anemia in chronic kidney disease (CKD) patients. This study aimed to compare the efficacy and safety of HIF-PHI vs epoetin and darbepoetin in CKD patients with anemia not undergoing dialysis. The PubMed, Embase, Cochrane Library, Web of Science, and clinicaltrials.gov databases were searched from inception to October 2019 for randomized controlled trials investigating different agents (six HIF-PHIs, epoetin, darbepoetin, and placebo) for treating CKD patients with anemia that did not undergo dialysis. The outcomes included a change in hemoglobin (Hb) levels and all-cause mortality. A total of 19 studies were included. Compared with the placebo, except for vadadustat (mean differences: 1.12, 95 % confidence interval [CI]: ‒0.11-2.35), the other drugs significantly increased Hb levels, with mean differences of 2.46 (95 % CI: 0.93-3.99) for desidustat, 1.81 (0.87-2.75) for enarodustat, 1.68 (0.64-2.72) for molidustat, 1.66 (0.89-2.44) for epoetin, 1.63 (0.69-2.56) for darbepoetin, 1.61 (0.99-2.22) for roxadustat, and 1.55 (0.74-2.36) for daprodustat. No differences were found in the Hb level elevations among these eight drugs. Compared with the placebo, there also was no significant association between the drugs and all-cause mortality (molidustat of RR, 0.39 [95 % CI, 0.06-2.59]; roxadustat, 0.40 (0.06-2.84); enarodustat, 0.33 (0.01-16.25); desidustat, 0.34 (0.01-17.00); epoetin, 0.50 (0.18-1.42); daprodustat, 0.54 (0.09-3.31); darbepoetin, 1.03 (0.65-1.65); and vadadustat, 1.43 (0.15-13.27)). No differences were observed in the all-cause mortality among the drugs. In conclusion, these HIF-PHIs are effective and relatively tolerant for treating anemia patients with CKD not undergoing dialysis. Further research should consider the limitations of our study to evaluate the value of these HIF-PHIs in clinical settings.

Topics: Aged; Aged, 80 and over; Anemia; Biomarkers; Darbepoetin alfa; Enzyme Inhibitors; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; Male; Middle Aged; Network Meta-Analysis; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Anemia has and will continue to be a central theme in medicine particularly as clinicians are treating a burgeoning population of complex multi-organ system processes. As a result of multiple randomized controlled trials (RCTs), meta-analyses, and societal recommendations overly restrictive paradigms and under-administration of erythropoiesis stimulating agents (ESAs) have likely been followed by clinicians among all specialties.. A review of anemia in the context of chronic kidney disease, hematologic malignancies, and cancer is presented with focus on the establishment of ESAs as integral in the treatment of anemia. Multiple RCTs and meta-analyses studying the use of ESAs are presented with focus upon their application to clinical practice. A 'compendium' is proffered describing the evolution, establishment, and implications of ESA administration initially among those with CKD with rapid subsequent application to the Hematology-Oncology population of patients. Literature search methodologies have included MEDLINE (1985-2020), PubMed (1996-2020), Cochrane Central Trials (1985-2020), EMBASE (2000-2020), and ClinicalTrials.gov (2000-2020).. Upon evaluation of risks and benefits of ESAs focused opinion and commentary is made supporting more liberal use of these agents and strongly suggesting that the current underlying treatment 'pendulum' has perhaps shifted too far to the 'under-treatment' side in many cases.

Topics: Anemia; Blood Transfusion; Combined Modality Therapy; COVID-19; Epoetin Alfa; Erythropoietin; Expert Testimony; Forecasting; Guideline Adherence; Hematinics; Hematologic Neoplasms; Hematopoiesis; Humans; Iron; Medicine; Meta-Analysis as Topic; Multicenter Studies as Topic; Myocardial Ischemia; Neoplasms; Observational Studies as Topic; Pandemics; Practice Guidelines as Topic; Practice Patterns, Physicians'; Randomized Controlled Trials as Topic; Receptors, Erythropoietin; Renal Dialysis; Renal Insufficiency, Chronic; SARS-CoV-2; Venous Thromboembolism

Anemia is a well-known complication of advanced CKD and treatment with erythropoietin analogues (epoetin) remains a key component of management. Although biologic agents, including epoetin, play an extremely important role in the treatment of various medical conditions, their cost can be prohibitive. As a result, several biosimilar agents have now been approved by the U.S. Food and Drug Administration. Biosimilar epoetin has been used in Europe since 2007. In this article, we will review biosimilar development and focus on the first approved biosimilar epoetin in the United States, epoetin alfa-epbx.

Topics: Anemia; Biosimilar Pharmaceuticals; Drug Approval; Drug Development; Epoetin Alfa; Europe; Hematinics; Humans; Renal Insufficiency, Chronic; United States

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis, leading to hematopoietic precursor cell apoptosis and peripheral blood cytopenias. Anemia is the most frequently experienced cytopenia and is the main cause of MDS symptoms, with fatigue and dyspnea contributing to reduced quality of life and increased morbidity. As MDS disease course and prognosis is influenced by disease factors, prognostic scoring systems have been developed for MDS to aid clinical and therapeutic decisions following diagnosis. Erythropoiesis- stimulating agents (ESAs) have been used for many years to treat anemia in patients with lower-risk MDS without chromosomal abnormalities. The use of ESAs is recommended by international clinical practice guidelines, due to the large body of evidence demonstrating their effectiveness in lower-risk MDS. In March 2017, the European Medicines Agency approved epoetin alfa for the treatment of anemia in lower-risk MDS patients, based on the results from a Phase 3 clinical trial and three European registry studies. The effectiveness of biosimilar epoetin alfa (Binocrit

Topics: Anemia; Clinical Protocols; Epoetin Alfa; Hematinics; Humans; Myelodysplastic Syndromes; Practice Guidelines as Topic

Biologics are widely used to manage the side effects of cancer treatment (e.g., epoetin alfa is used to treat chemotherapy-induced anemia [CIA] and granulocyte colony-stimulating factors [G-CSFs] are used to treat chemotherapy-induced neutropenia [CIN]). As several patents for biologics used in cancer treatment have expired, a number of companies have developed supportive care biosimilars (e.g., epoetin alfa biosimilar, filgrastim biosimilar, pegfilgrastim biosimilar).. The objective of this study was to synthesize current evidence on the efficacy and safety of supportive care biosimilars compared with their reference biologics in oncology.. We searched PubMed, Embase, the Cochrane library, ClinicalTrials.gov, ISI Web of Science and several Chinese databases from their inception dates to December 31, 2018 for randomized controlled trials (RCTs) or comparative observational studies that compared the efficacy and safety of supportive care biosimilars and their reference biologics in oncology. We pooled results separately for RCTs and observational studies, as such studies involve different patient populations and are designed differently. We pooled binary outcomes using risk ratios (RR) with confidence intervals (CIs) and continuous outcomes using weighted mean differences (WMD) with 95% CIs, then conducted subgroup and sensitivity analyses. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the quality of evidence.. We identified 28 studies that compared biosimilars of G-CSF or epoetin alfa: one RCT and five cohort studies (total N = 2816) of epoetin alfa biosimilars, and 13 RCTs and 9 cohort studies (total N = 23,043) of G-CSF biosimilars [corrected]. Despite involving different populations, RCTs and observational studies comparing biosimilars and reference biologics indicated similar efficacy and safety results. Overall, there was no statistically significant difference in any efficacy or safety outcomes between any biosimilars and their corresponding original biologics (all p > 0.05). The quality of GRADE evidence of efficacy and safety outcomes was moderate or low. Findings were robust for all prespecified subgroup and sensitivity analyses.. Existing evidence suggests highly comparable efficacy and safety profiles for supportive care biosimilars and their reference biologics in oncology.

Topics: Anemia; Antineoplastic Agents; Biosimilar Pharmaceuticals; Chemotherapy-Induced Febrile Neutropenia; Epoetin Alfa; Filgrastim; Hematologic Agents; Humans; Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome

Several Erythropoiesis-stimulating agents (ESAs) are available to treat anemia in patients with chronic kidney disease (CKD). Questions about the comparability of such therapeutic options are not purely a regulatory or economical matter. Appropriate use of originator or biosimilar in these patients need to be supported by clinical data. Regarding the prevention of blood transfusion, reduction of fatigue, breathlessness and mortality or cardiovascular events, a summary of the comparative efficacy and safety data of these drugs is lacking.. We performed a systematic literature search of CENTRAL, PubMed, and Embase through November 11, 2015. Our inclusion criteria encompassed randomized, controlled clinical trials that evaluated the comparative effectiveness of different ESAs originators and/or biosimilar. The considered participants were adults aged 18 years or older with anemia due to CKD. The overall quality of evidence was assessed using the GRADE system.. We identified 30 eligible studies including 7843 patients with CKD, and 21/30 studies included patients using hemodialysis or peritoneal dialysis. Compared with ESA biosimilars, epoetin α did not statistically differ for any of the ten measured outcomes. The quality of evidence varied from low to very low. In the comparison between epoetin α vs. darbepoetin α, no differences were observed for all outcomes, but blood transfusions showed favorable results for darbepoetin α: RR 2.18 (1.31-3.62). The quality of evidence varied from low to very low. No differences were observed between epoetin β and methoxy polyethylene glycol-epoetin β, and between darbepoetin α and methoxy polyethylene glycol-epoetin β, the quality of evidence varied from moderate to very low.. Data from 31 included studies allowed to pool data in meta-analysis related to four different comparisons and eleven outcome measures. Nevertheless, only one result was statistically significant in favor of darbepoetin α in the comparison with epoetin α concerning blood transfusions. For all the other outcomes and comparisons, we did not find any differences in terms of efficacy and security between the EPO considered. The quality of evidence is quite low, and further research could change these results. Further high quality studies examining the comparative effectiveness of ESAs need to be conducted.

Topics: Adult; Anemia; Biosimilar Pharmaceuticals; Blood Transfusion; Comparative Effectiveness Research; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Insufficiency, Chronic

Topics: Anemia; Animals; Biosimilar Pharmaceuticals; Clinical Trials as Topic; Epoetin Alfa; Erythropoiesis; Evidence-Based Medicine; Hematinics; Humans; Renal Insufficiency, Chronic; Therapeutic Equivalency; Treatment Outcome

High-quality, safe, and effective biosimilars have the potential to increase access to biological therapies worldwide and to reduce cancer care costs. The European Medicines Agency (EMA) was the first regulatory authority to establish legislative procedures for the approval of biosimilars when they published their guidelines on similar biological medicinal products in 2005. Biosimilar epoetins were first approved in 2007, and a wealth of data has been collected over the last decade. Two biosimilar epoetins (under five commercial names) have been approved by the EMA so far. The availability of epoetin biosimilars generated discussion among the oncology community regarding prescribing these products, their efficacy, and their safety. These agents are approved only if they are shown in extensive analytical and clinical testing to have comparable quality, safety, and efficacy to the reference medicine, and real-world studies provide further data that biosimilar epoetins are an effective and well-tolerated option for the treatment of chemotherapy-induced anemia in patients with cancer. Other countries have adopted similar regulatory pathways to those in Europe and have approved epoetin biosimilars. The now extensive European experience with biosimilar epoetins should reassure regulators from other territories.

Topics: Anemia; Antineoplastic Agents; Biosimilar Pharmaceuticals; Epoetin Alfa; Europe; Humans

While prescribing biosimilars to patients naive to a biologic treatment is a well-accepted practice, switching clinically stable patients from an originator to a biosimilar is an issue for clinicians. Well-designed clinical trials and real-world data which study the consequences of switching from an originator biologic treatment to its biosimilar alternative are limited, especially for monoclonal antibodies. Areas covered: A systematic literature review was conducted on PubMed to identify evidence of the consequences of switching from original biologics to biosimilars. References of included papers were also scrutinized. After a title-, abstract- and full text screening, out of the 153 original hits and 77 additional ones from screening the references, 58 papers (12 empirical papers, 5 systematic reviews and 41 non-empirical papers) were included. Expert opinion: Preventing patients on biologic medicines from switching to biosimilars due to anticipated risks seems to be disproportional compared to the expected cost savings and/or improved patient access. Indeed, it is the opinion of the authors that the concern of switching to biosimilars is overhyped.

Topics: Anemia; Biosimilar Pharmaceuticals; Databases, Factual; Epoetin Alfa; Health Care Costs; Humans; Inflammatory Bowel Diseases; Kidney Failure, Chronic; Neoplasms; Red-Cell Aplasia, Pure; Rheumatic Diseases; Risk

With increasing knowledge of the risks associated with receiving blood transfusions, a new paradigm of bloodless medicine is needed. Principles of bloodless medicine include careful monitoring for obvious and hidden anemias, rapid intervention, minimizing blood losses from laboratory testing and procedures, and careful management of bleeding diatheses. As evidence is revealed and refined, standard treatment of anemia in the intensive care unit will include erythropoietin-stimulating agents, iron, folate, and vitamin B12, which will reduce risks associated with blood transfusions.

Topics: Anemia; Blood Transfusion; Bloodless Medical and Surgical Procedures; Critical Care Nursing; Critical Illness; Epoetin Alfa; Heart Failure; Hematinics; Humans; Intensive Care Units

Continuous erythropoiesis receptor activator (CERA) is a newer, longer acting ESA which might be preferred to other ESAs (epoetin or darbepoetin) based on its lower frequency of administration. Different dosing requirements and molecular characteristics of CERA compared with other ESAs may lead to different health outcomes (mortality, cardiovascular events, quality of life) in people with anaemia and chronic kidney disease (CKD).. To assess benefits and harms of CERA compared with other epoetins (darbepoetin alfa and epoetin alfa or beta) or placebo/no treatment or CERA with differing strategy of administration for anaemia in individuals with CKD.. We searched the Cochrane Kidney and Transplant Specialised Register to 13 June 2017 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.. We included randomised controlled trials (RCTs) of at least three months' duration, comparing CERA with a different ESA (darbepoetin alfa or epoetin alfa or beta) or placebo or standard care or versus CERA with different strategies for administration in people with any stage of CKD.. Data were extracted by two independent investigators. We summarised patient-centred outcomes (all-cause and cardiovascular mortality, major adverse cardiovascular events, red cell blood transfusion, iron therapy, cancer, hypertension, seizures, dialysis vascular access thrombosis, drug injection-related events, hyperkalaemia and health-related quality of life and haemoglobin levels) using random effects meta-analysis. Treatment estimates were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean differences or standardized mean difference with 95% CI for continuous outcomes.. We included 27 studies involving 5410 adults with CKD. Seven studies (1273 participants) involved people not requiring dialysis, 19 studies (4209 participants) involved people treated with dialysis and one study (71 participants) evaluated treatment in recipients of a kidney transplant. Treatment was given for 24 weeks on average. No data were available for children with CKD. Studies were generally at high or unclear risk of bias from allocation concealment and blinding of outcomes. Only two studies masked participants and investigators to treatment allocation. One study compared CERA with placebo, nine studies CERA with epoetin alfa or beta, nine studies CERA with darbepoetin alfa, and two studies compared CERA with epoetin alfa or beta and darbepoetin alfa. Three studies assessed the effects of differing frequencies of CERA administration and five assessed differing CERA doses.There was low certainty evidence that CERA had little or no effects on mortality (RR 1.07, 95% CI 0.73 to 1.57; RR 1.11, 95% CI 0.75 to 1.65), major adverse cardiovascular events (RR 5.09, 95% CI 0.25 to 105.23; RR 5.56, 95% CI 0.99 to 31.30), hypertension (RR 1.01, 95% CI 0.75 to 1.37; RR 1.00, 95% CI 0.79 to 1.28), need for blood transfusion (RR 1.02, 95% CI 0.72 to 1.46; RR 0.94, 95% CI 0.55 to 1.61), or additional iron therapy (RR 1.03, 95% CI 0.91 to 1.15; RR 0.99, 95% CI 0.95 to 1.03) compared to epoetin alfa/beta or darbepoetin alfa respectively. There was insufficient evidence to compare the effect of CERA to placebo on clinical outcomes. Only one low quality study reported that CERA compared to placebo might lead to little or no difference in the risk of major cardiovascular events (RR 2.97, 95% CI 0.31 to 28.18) and hypertension ((RR 0.73, 95% CI 0.35 to 1.52). There was low certainty evidence that different doses (higher versus lower) or frequency (twice versus once monthly) of CERA administration had little or no different effect on all-cause mortality (RR 3.95, 95% CI 0.17 to 91.61; RR 0.97, 95% CI 0.56 to 1.66), hypertension (RR 0.45, 95% CI 0.08 to 2.52; RR 0.85, 95% CI 0.60 to 1.21), and blood cell transfusions (RR 4.16, 95% CI 0.89 to 19.53; RR 0.91, 95% CI 0.51 to 1.62). No studies reported comparative treatment effects of different ESAs on health-related quality of life.. There is low certainty evidence that CERA has little or no effects on patient-centred outcomes compared with placebo, epoetin alfa or beta or darbepoetin alfa for adults with CKD. The effects of CERA among children who have CKD have not studied in RCTs.

Topics: Adult; Aged; Anemia; Cardiovascular Diseases; Cause of Death; Darbepoetin alfa; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Humans; Hypertension; Middle Aged; Polyethylene Glycols; Publication Bias; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic; Thrombosis

Nephrotic syndrome is one of the most common glomerular diseases that affect in children. Complications may occur in nephrotic syndrome as a result of the disease itself as well as its treatment. Most of these complications result from excessive urinary protein losses, and control of proteinuria is the most effective treatment strategy. Anemia is one of the many complications seen in patients with persistent nephrotic syndrome and may occur as a result of excessive urinary losses of iron, transferrin, erythropoietin, transcobalamin and/or metals. This leads to a deficiency of substrates necessary for effective erythropoiesis, requiring supplementation in order to correct the anemia. Supplementation of iron and erythropoietin alone often does not lead to correction of the anemia, suggesting other possible mechanisms which need further investigation. A clear understanding of the pathophysiologic mechanisms of anemia in nephrotic syndrome is necessary to guide appropriate therapy, but only limited evidence is currently available on the precise etiologic mechanisms of anemia in nephrotic syndrome. In this review we focus on the current state of knowledge on the pathogenesis of anemia in nephrotic syndrome.

Topics: Anemia; Child; Epoetin Alfa; Erythropoiesis; Erythropoietin; Gluconates; Hematinics; Humans; Iron; Kidney; Nephrotic Syndrome; Proteinuria; Renal Elimination; Transferrin; Treatment Outcome; Vitamins

The benefits of erythropoiesis-stimulating agents (ESA) for chronic kidney disease (CKD) patients have been previously demonstrated. However, the efficacy and safety of short-acting epoetins administered at larger doses and reduced frequency as well as of new epoetins and biosimilars remains uncertain.. This review aimed to evaluate the benefits and harms of different routes, frequencies and doses of epoetins (epoetin alpha, epoetin beta and other short-acting epoetins) for anaemia in adults and children with CKD not receiving dialysis.. We searched the Cochrane Kidney and Transplant Specialised Register to 12 September 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.. We included randomised control trials (RCTs) comparing different frequencies, routes, doses and types of short-acting ESAs in CKD patients.. Two authors independently assessed study eligibility and four authors assessed risk of bias and extracted data. Results were expressed as risk ratio (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) with 95% confidence intervals (CI) was used. Statistical analyses were performed using the random-effects model.. We identified 14 RCTs (2616 participants); nine studies were multi-centre and two studies involved children. The risk of bias was high in most studies; only three studies demonstrated adequate random sequence generation and only two studies were at low risk of bias for allocation concealment. Blinding of participants and personnel was at low risk of bias in one study. Blinding of outcome assessment was judged at low risk in 13 studies as the outcome measures were reported as laboratory results and therefore unlikely to be influenced by blinding. Attrition bias was at low risk of bias in eight studies while selective reporting was at low risk in six included studies.Four interventions were compared: epoetin alpha or beta at different frequencies using the same total dose (six studies); epoetin alpha at the same frequency and different total doses (two studies); epoetin alpha administered intravenously versus subcutaneous administration (one study); epoetin alpha or beta versus other epoetins or biosimilars (five studies). One study compared both different frequencies of epoetin alpha at the same total dose and at the same frequency using different total doses.Data from only 7/14 studies could be included in our meta-analyses. There were no significant differences in final haemoglobin (Hb) levels when dosing every two weeks was compared with weekly dosing (4 studies, 785 participants: MD -0.20 g/dL, 95% CI -0.33 to -0.07), when four weekly dosing was compared with two weekly dosing (three studies, 671 participants: MD -0.16 g/dL, 95% CI -0.43 to 0.10) or when different total doses were administered at the same frequency (four weekly administration: one study, 144 participants: MD 0.17 g/dL 95% CI -0.19 to 0.53).Five studies evaluated different interventions. One study compared epoetin theta with epoetin alpha and found no significant differences in Hb levels (288 participants: MD -0.02 g/dL, 95% CI -0.25 to 0.21). One study found significantly higher pain scores with subcutaneous epoetin alpha compared with epoetin beta. Two studies (165 participants) compared epoetin delta with epoetin alpha, with no results available since the pharmaceutical company withdrew epoetin delta for commercial reasons. The fifth study comparing the biosimilar HX575 with epoetin alpha was stopped after patients receiving HX575 subcutaneously developed anti-epoetin antibodies and no results were available.Adverse events were poorly reported in all studies and did not differ signif. Epoetin alpha given at higher doses for extended intervals (two or four weekly) is non-inferior to more frequent dosing intervals in maintaining final Hb levels with no significant differences in adverse effects in non-dialysed CKD patients. However the data are of low methodological quality so that differences in efficacy and safety cannot be excluded. Further large, well designed, RCTs with patient-centred outcomes are required to assess the safety and efficacy of large doses of the shorter acting ESAs, including biosimilars of epoetin alpha, administered less frequently compared with more frequent administration of smaller doses in children and adults with CKD not on dialysis.

Topics: Adult; Anemia; Child; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobin A; Humans; Injections, Intravenous; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

Epoetin alfa (EPO) and darbepoetin alfa (DPO) are erythropoiesis-stimulating agents that are widely and interchangeably used for the treatment of anemia in patients with advanced chronic kidney disease and end-stage renal disease. No study has specifically compared the risks of hard study outcomes between EPO and DPO, including mortality.. Systematic review of the literature and meta-analysis.. Patients enrolled in randomized trials comparing EPO versus DPO for the treatment of anemia in adults with chronic kidney disease, including those requiring dialysis.. We conducted a systematic search of the literature (PubMed, CENTRAL, SCOPUS, and EMBASE, all years) and industry resources, using predefined search terms and data abstraction tools. We then summarized key characteristics and findings of these trials and performed a random-effects meta-analysis of trials with at least 3 months' duration to identify the summary OR of mortality between patients randomly assigned to DPO versus EPO.. DPO versus EPO.. All-cause mortality.. We identified 9 trials that met the stated inclusion criteria. Overall, 2,024 patients were included in the meta-analysis, of whom 126 died during follow-up, which ranged from 20 to 52 weeks. We found no significant difference in mortality between patients randomly assigned to DPO versus EPO (OR, 1.33; 95% CI, 0.88-2.01). No treatment heterogeneity across studies was detected (Q statistic=4.60; P=0.8).. Generalizability to nontrial populations is uncertain.. Few trials directly comparing DPO and EPO have been conducted and follow-up was limited. In aggregate, no effect of specific erythropoiesis-stimulating agent on mortality was identified, but the confidence limits were wide and remained compatible with considerable harm from DPO. Absent adequately powered randomized trials, observational postmarketing comparative effectiveness studies comparing these erythropoiesis-stimulating agents are required to better characterize the long-term safety profiles of these agents.

Topics: Anemia; Cause of Death; Darbepoetin alfa; Double-Blind Method; Epoetin Alfa; Erythropoietin; Half-Life; Hematinics; Humans; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

Erythropoiesis-stimulating agents (ESAs) increase red blood cell production in patients with chemotherapy-induced anemia (CIA). In Europe, short-acting ESAs (epoetin alfa, epoetin beta, epoetin zeta, and epoetin theta) and a long-acting ESA (darbepoetin alfa) are available to treat CIA.. This systematic review aimed to determine potential dose efficiency associated with the use of different ESAs for the treatment of CIA according to European labeling.. A systematic review of ESA studies with starting doses according to European labeling was conducted according to published methodology. Measures of dose efficiency were defined as mean weekly doses to achieve target hemoglobin level or final dose and dose adjustments (dose increase, decrease, or withheld). Electronic databases and grey literature sources were searched up to July 2012. Data were selected for analysis using an evidence hierarchy and quantitatively analyzed to assess statistical homogeneity. Where pooling of data was not appropriate, a narrative summary with descriptive statistics (medians and ranges) was reported.. Fifty-five studies met the inclusion criteria. Twenty-five studies considered to represent the highest level of evidence were extracted and included in the analysis. The analysis showed a high degree of statistical heterogeneity, often precluding meta-analysis. The patients included in the analysis were representative of those encountered in clinical practice, and patient characteristics were similar between the short-acting and the darbepoetin alfa groups. Mean weekly doses appeared ~30% lower with darbepoetin alfa versus short-acting ESAs (median, 136.5 μg or 27,300 IU [range, 21,560-38,260 IU] vs 38,230 IU [range, 31,634-42,714 IU], respectively), resulting in a mean weekly dose ratio of 1:280. Darbepoetin alfa patients appeared to need fewer dose increases compared with short-acting ESAs (pooled, 0.75%; I(2) = 21% vs median 26.6% [range, 7.6%-44.6%]) and more dose decreases (median, 74% [range, 57%-75%] vs 22% [range, 2.8%-59%]). A similar percentage of darbepoetin alfa and short-acting ESA patients required a dose to be withheld (20% and 33% [2 studies] vs median 33.2% [range, 12.6%-51.1%]).. Statistical heterogeneity between studies was high, although clinically the studies represented medical practice. Without randomized clinical trials directly comparing darbepoetin alfa and short-acting ESAs, these findings are tentative and future research is warranted. This review shows that good-quality, reliable data from head-to-head trials are lacking. The best available evidence comes from prospective ESA-arm data. Mean weekly doses, dose increases, and dose decreases suggest a dose efficiency for darbepoetin alfa compared with short-acting ESAs.

Topics: Anemia; Darbepoetin alfa; Databases, Factual; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Humans; Middle Aged; Prospective Studies; Recombinant Proteins

Erythropoiesis-stimulating agents are used to treat anaemia in people with chronic kidney disease (CKD). Several agents are available including epoetin alfa or beta as well as agents with a longer duration of action, darbepoetin alfa and methoxy polyethylene glycol-epoetin beta.. To assess the benefits and harms of darbepoetin alfa to treat anaemia in adults and children with CKD (stages 3 to 5, 5D, and kidney transplant recipients).. We searched the Cochrane Renal Group's Specialised Register (to 13 January 2014) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE.. We included randomised controlled trials of any darbepoetin alfa treatment of at least three months duration in adults or children with CKD (any stage).. Data were extracted by two independent investigators. Patient-centred outcomes (need for blood transfusion, iron therapy, progression of kidney disease, total and cardiovascular mortality, cardiovascular events, cancer, hypertension, seizures, and health-related quality of life) and other outcomes (haemoglobin levels) were assessed using random effects meta-analysis. We calculated risk ratios for dichotomous outcomes and mean differences for continuous outcomes, both with 95% confidence intervals.. We identified 32 studies comprising 9414 participants; 21 studies in 8328 participants could be included in our meta-analyses. One study (4038 participants) compared darbepoetin alfa to placebo, 16 studies (2955 participants) compared darbepoetin alfa to epoetin alfa or beta, four studies (1198 participants) compared darbepoetin alfa to methoxy polyethylene glycol-epoetin beta, three studies (420 participants) compared more frequent with less frequent darbepoetin alfa administration and four studies (303 participants) compared intravenous with subcutaneous darbepoetin alfa administration.In a single large study, darbepoetin alfa reduced the need for blood transfusion and iron therapy compared with placebo in adults with CKD stage 3 to 5, but had little or no effect on survival, increased risks of hypertension, and had uncertain effects on quality of life. Data comparing darbepoetin alfa with epoetin alfa or beta or methoxy polyethylene glycol-epoetin beta were sparse and inconclusive. Comparisons of differing dosing schedules and routes of administration were compared in small numbers of participants and studies. Evidence for treatment effects of darbepoetin alfa were particularly limited for children with CKD, adults with CKD stage 5D, and recipients of a kidney transplant.Studies included in this review were generally at high or unclear risk of bias for all items (random sequence generation, allocation concealment, incomplete outcome data, blinding of participants and personnel, blinding of outcome assessment, selective outcome reporting, intention to treat analysis and other sources of bias). One large study comparing darbepoetin alfa with placebo was at low risk of bias for most items assessed.. Data suggest that darbepoetin alfa effectively reduces need for blood transfusions in adults with CKD stage 3 to 5, but has little or no effect on mortality or quality of life. The effects of darbepoetin alfa in adults with CKD stage 5D and kidney transplant recipients and children with CKD remain uncertain as do the relative benefits and harms of darbepoetin alfa compared with other ESAs (epoetin alfa or beta and methoxy polyethylene glycol-epoetin beta).

Topics: Adult; Anemia; Child; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Transplantation; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Insufficiency, Chronic

Erythropoiesis stimulating agents [erythropoietin (EPO)] have been recommended to treat anaemic patients who cannot receive or refuse blood tranfusion ('untransfusable' patients).. The objective of the study was to quantify the association of EPO use with haemoglobin (Hgb) recovery in anaemic untransfusable hospitalised patients.. EPO treated anaemic untransfusable patients were identified through the combination of a retrospective case review and a systematic review of the medical literature. Literature reports of untransfusable patients not treated with any EPO were used as a comparator group. Hgb concentrations before and following EPO use were abstracted and used to determine the rate of Hgb recovery for each case. Multilevel mixed effects modelling was used to determine the association of Hgb recovery with EPO use.. A total of 76 EPO treated cases (19 cases from the retrospective hospital case review and 57 from the literature), and 33 non-EPO treated comparator patients from the literature were included in the study. Hgb increased similarly over time in all groups at an overall mean standard error (SE) rate of 0·13 (0·01) g dL(-1)  day(-1) . The Hgb recovery rate was higher in patients with lower baseline Hgb, regardless of EPO use. No association was found between the rate of Hgb recovery and EPO use, dose or therapy duration.. In anaemic, 'untransfusable' hospitalised patients, EPO use was not associated with increased Hgb recovery at anytime within 28 days.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Models, Biological; Recombinant Proteins; Recovery of Function; Retrospective Studies

Topics: Anemia; Biosimilar Pharmaceuticals; Epoetin Alfa; Erythropoietin; Europe; Hematinics; Humans; Hypoxia-Inducible Factor 1; Kidney Failure, Chronic; Recombinant Proteins; United States; United States Food and Drug Administration

Several erythropoiesis-stimulating agents (ESAs) are available for treating anaemia in people with chronic kidney disease (CKD). Their relative efficacy (preventing blood transfusions and reducing fatigue and breathlessness) and safety (mortality and cardiovascular events) are unclear due to the limited power of head-to-head studies.. To compare the efficacy and safety of ESAs (epoetin alfa, epoetin beta, darbepoetin alfa, or methoxy polyethylene glycol-epoetin beta, and biosimilar ESAs, against each other, placebo, or no treatment) to treat anaemia in adults with CKD.. We searched the Cochrane Renal Group's Specialised Register to 11 February 2014 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.. Randomised controlled trials (RCTs) that included a comparison of an ESA (epoetin alfa, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, or biosimilar ESA) with another ESA, placebo or no treatment in adults with CKD and that reported prespecified patient-relevant outcomes were considered for inclusion.. Two independent authors screened the search results and extracted data. Data synthesis was performed by random-effects pairwise meta-analysis and network meta-analysis. We assessed for heterogeneity and inconsistency within meta-analyses using standard techniques and planned subgroup and meta-regression to explore for sources of heterogeneity or inconsistency. We assessed our confidence in treatment estimates for the primary outcomes within network meta-analysis (preventing blood transfusions and all-cause mortality) according to adapted GRADE methodology as very low, low, moderate, or high.. We identified 56 eligible studies involving 15,596 adults with CKD. Risks of bias in the included studies was generally high or unclear for more than half of studies in all of the risk of bias domains we assessed; no study was low risk for allocation concealment, blinding of outcome assessment and attrition from follow-up. In network analyses, there was moderate to low confidence that epoetin alfa (OR 0.18, 95% CI 0.05 to 0.59), epoetin beta (OR 0.09, 95% CI 0.02 to 0.38), darbepoetin alfa (OR 0.17, 95% CI 0.05 to 0.57), and methoxy polyethylene glycol-epoetin beta (OR 0.15, 95% CI 0.03 to 0.70) prevented blood transfusions compared to placebo. In very low quality evidence, biosimilar ESA therapy was possibly no better than placebo for preventing blood transfusions (OR 0.27, 95% CI 0.05 to 1.47) with considerable imprecision in estimated effects. We could not discern whether all ESAs were similar or different in their effects on preventing blood transfusions and our confidence in the comparative effectiveness of different ESAs was generally very low. Similarly, the comparative effects of ESAs compared with another ESA, placebo or no treatment on all-cause mortality were imprecise.All proprietary ESAs increased the odds of hypertension compared to placebo (epoetin alfa OR 2.31, 95% CI 1.27 to 4.23; epoetin beta OR 2.57, 95% CI 1.23 to 5.39; darbepoetin alfa OR 1.83, 95% CI 1.05 to 3.21; methoxy polyethylene glycol-epoetin beta OR 1.96, 95% CI 0.98 to 3.92), while the effect of biosimilar ESAs on developing hypertension was less certain (OR 1.18, 95% CI 0.47 to 2.99). Our confidence in the comparative effects of ESAs on hypertension was low due to considerable imprecision in treatment estimates. The comparative effects of all ESAs on cardiovascular mortality, myocardial infarction (MI), stroke, and vascular access thrombosis were uncertain and network analyses for major cardiovascular events, end-stage kidney disease (ESKD), fatigue and breathlessness were not possible. Effects of ESAs on fatigue were described heterogeneously in the available studies in ways that were not useable for analyses.. In the CKD setting, there is currently insufficient evidence to suggest the superiority of any ESA formulation based on available safety and efficacy data. Directly comparative data for the effectiveness of different ESA formulations based on patient-centred outcomes (such as quality of life, fatigue, and functional status) are sparse and poorly reported and current research studies are unable to inform care. All proprietary ESAs (epoetin alfa, epoetin beta, darbepoetin alfa, and methoxy polyethylene glycol-epoetin beta) prevent blood transfusions but information for biosimilar ESAs is less conclusive. Comparative treatment effects of different ESA formulations on other patient-important outcomes such as survival, MI, stroke, breathlessness and fatigue are very uncertain.For consumers, clinicians and funders, considerations such as drug cost and availability and preferences for dosing frequency might be considered as the basis for individualising anaemia care due to lack of data for comparative differences in clinical benefits and harms.

Topics: Adult; Anemia; Biosimilar Pharmaceuticals; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Hypertension; Polyethylene Glycols; Recombinant Proteins; Renal Insufficiency, Chronic

Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disorder that mainly affects the small joints of the hands and feet. Erythropoiesis-stimulating agents have been used to treat anemia, one of the extra-articular manifestations of RA. Although anemia is less of a problem now because of the reduction in inflammation due to disease-modifying antirheumatic drugs (DMARDs), it could still be an issue in countries where DMARDs are not yet accessible.. We assessed the clinical benefits and harms of erythropoiesis-stimulating agents for anemia in rheumatoid arthritis.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (issue 7 2012), Ovid MEDLINE and Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations (1948 to 7 August 2012), OVID EMBASE (1980 to 7 August 2012), LILACS (1982 to 7 August 2012), the Clinical Trials Search Portal of the World Health Organization, reference lists of the retrieved publications and review articles. We did not apply any language restrictions.. We included randomized controlled trials (RCTs) in patients aged 16 years or over, with a diagnosis of rheumatoid arthritis affected by anemia. We considered health-related quality of life, fatigue and safety as the primary outcomes.. Two authors independently performed trial selection, risk of bias assessment, and data extraction. We estimated difference in means with 95% confidence intervals (CIs) for continuous outcomes. We estimated risk ratios with 95% CIs for binary outcomes.. We included three RCTs with a total of 133 participants. All trials compared human recombinant erythropoietin (EPO), for different durations (8, 12 and 52 weeks), versus placebo. All RCTs assessed health-related quality of life. All trials had high or unclear risk of bias for most domains, and were sponsored by the pharmaceutical industry. Two trials administered EPO by a subcutaneous route while the other used an intravenous route.We decided not to pool results from trials, due to inconsistencies in the reporting of results.Health-related quality of life: subcutaneous EPO - one trial with 70 patients at 52 weeks showed a statistically significant difference in improvement of patient global assessment (median and interquartile range 3.5 (1.0 to 6.0) compared with placebo 4.5 (2.0 to 7.5) (P = 0.027) on a VAS scale (0 to 10)). The other shorter term trials (12 weeks with subcutaneous EPO and eight weeks with intravenous administration) did not find statistically significant differences between treatment and control groups in health-related quality of life outcomes.Change in hemoglobin: both trials of subcutaneous EPO showed a statistically significant difference in increasing hemoglobin levels; (i) at 52 weeks (one trial, 70 patients), intervention hemoglobin level (median 134, interquartile range 110 to 158 g/litre) compared with the placebo group level (median 112, interquartile range; 86 to 128 g/litre) (P = 0.0001); (ii) at 12 weeks (one trial, 24 patients) compared with placebo (difference in means 8.00, 95% CI 7.43 to 8.57). Intravenous EPO at eight weeks showed no statistically significant difference in increasing hematocrit level for EPO versus placebo (difference in means 4.69, 95% CI -0.17 to 9.55; P = 0.06).Information on withdrawals due to adverse events was not reported in two trials, and one trial found no serious adverse events leading to withdrawals. None of the trials reported withdrawals due to high blood pressure, or to lack of efficacy or to fatigue.. We found conflicting evidence for erythropoiesis-stimulating agents to increase quality of life and hemoglobin level by treating anemia in patients with rheumatoid arthritis. However, this conclusion is based on randomized controlled trials with a high risk of bias, and relies on trials assessing human recombinant erythropoietin (EPO). The safety profile of EPO is unclear. Future trials assessing erythropoiesis-stimulating agents for anemia in rheumatoid arthritis should be conducted by independent researchers and reported according to the CONSORT statements. Trials should be based on Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) and The Patient-Centered Outcomes Research Institute (PCORI) approaches for combining both clinician and patient perspectives.

Topics: Anemia; Arthritis, Rheumatoid; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobin A; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Iron; Recombinant Proteins; Renal Insufficiency, Chronic

Erythropoiesis-stimulating agents (ESAs) prevent transfusions among anemic patients with chronic kidney disease (CKD). Clinical trials, meta-analyses, and guidelines identify arterial and venous thromboembolism as well as myocardial event risks with the traditional ESAs, erythropoietin (EPO), and darbepoietin. Side effects of anemia treatment, considering frequency and dosage of treatment as well as targeted hemoglobin levels when utilizing ESAs, greatly impact overall well-being and the quality of life. There is a need for less frequent but equally effective ESAs in this setting.. The three generations of ESAs used in CKD-associated anemia are described. Cost effectiveness of the utilization of these therapies, in addition to emerging therapies, is also presented. The few clinical and controlled trials only highlight the need for clarity in molecular biology surrounding the components that control EPO levels and utilization.. Anemia associated with CKD is an important area for development of newer therapies which are potentially safer and more convenient to administer.

Topics: Anemia; Darbepoetin alfa; Drug Discovery; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Quality of Life; Recombinant Proteins; Renal Insufficiency, Chronic

Targeting higher hemoglobin levels with erythropoiesis-stimulating agents (ESAs) to treat the anemia of chronic kidney disease (CKD) is associated with increased cardiovascular risk.. Metaregression analysis examining the association of ESA dose with adverse outcomes independent of target or achieved hemoglobin level.. Patients with anemia of CKD irrespective of dialysis status.. We searched MEDLINE (inception to August 2010) and bibliographies of published meta-analyses and selected randomized controlled trials assessing the efficacy of ESAs for the treatment of anemia in adults with CKD, with a minimum 3-month duration. Two authors independently screened citations and extracted relevant data. Individual study arms were treated as cohorts and constituted the unit of analysis.. ESA dose standardized to a weekly epoetin alfa equivalent, and hemoglobin levels.. All-cause and cardiovascular mortality, cardiovascular events, kidney disease progression, or transfusion requirement.. 31 trials (12,956 patients) met the criteria. All-cause mortality was associated with higher (per epoetin alfa-equivalent 10,000-U/wk increment) first-3-month mean ESA dose (incidence rate ratio [IRR], 1.42; 95% CI, 1.10-1.83) and higher total-study-period mean ESA dose (IRR, 1.09; 95% CI, 1.02-1.18). First-3-month ESA dose remained significant after adjusting for first-3-month mean hemoglobin level (IRR, 1.48; 95% CI, 1.02-2.14), as did total-study-period mean ESA dose adjusting for target hemoglobin level (IRR, 1.41; 95% CI, 1.08-1.82). Parameter estimates between ESA dose and cardiovascular mortality were similar in magnitude and direction, but not statistically significant. Higher total-study-period mean ESA dose also was associated with increased rate of hypertension, stroke, and thrombotic events, including dialysis vascular access-related thrombotic events.. Use of study-level aggregated data; use of epoetin alfa-equivalent doses; lack of adjustment for confounders.. In patients with CKD, higher ESA dose might be associated with all-cause mortality and cardiovascular complications independent of hemoglobin level.

Topics: Aged; Anemia; Cardiovascular Diseases; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Recombinant Proteins; Regression Analysis; Renal Insufficiency, Chronic; Risk Factors; Treatment Outcome

Biosimilars have been developed for several biologic therapeutic agents, including erythropoiesis-stimulating agents (ESAs). However, biosimilars cannot be assumed to be completely identical to the reference product, nor can two different biosimilars of the same reference product be considered equivalent. Accordingly, standards for approving biosimilars are distinct from those for generic versions of conventional pharmaceuticals.By late 2007, two biosimilar epoetins (HX575 and SB309) had been approved by the European Medicines Agency (EMA), following a series of pharmacokinetic and pharmacodynamic equivalence studies, as well as phase 3 clinical comparability evaluations. Additionally, the results of a limited number of postauthorization interventional or observational studies and quality comparisons were published subsequently on both products.The reported differences in glycosylation profiles between these epoetin biosimilars and their reference product, as well as the lack of long-term safety and efficacy evaluation, could indicate a need to develop a more comprehensive analysis of the available data, and to evaluate the post-authorization real-life data, in order to gain a better understanding of any potential implications of molecular structural or formulation differences on longterm safety and effectiveness.Switching between an original reference ESA and a biosimilar (and possibly also switching between biosimilar versions of the same product) should be regarded as a change in clinical management. Clinicians need to be fully involved in such decisions. Prescribing by brand name will prevent unintentional substitution by pharmacists and allow for effective pharmacovigilance, in accordance with recent EU directives. In this review, the authors have analyzed most of the published information on the two epoetin biosimilars, HX575 and SB309, to highlight the points that healthcare providers may need to consider when assessing an epoetin biosimilar.

Topics: Anemia; Biosimilar Pharmaceuticals; Epoetin Alfa; Erythropoietin; Europe; Hematinics; Humans; Pharmacovigilance; Recombinant Proteins; Therapeutic Equivalency

Myelodysplastic syndromes (MDS) are heterogeneous clonal diseases characterized by cytopenias resulting from ineffective hemopoiesis. Anemia affects the vast majority of patients with MDS and contributes substantially to their symptoms. For more than 20 years, recombinant human erythropoietin has been available for clinical use, and it has been employed in an attempt to relieve MDS-related anemia. Erythropoietin-alpha, erythropoietin-beta, and more recently darbepoetin have been found to increase hemoglobin levels and abolish transfusion dependence in 19%-68% of MDS cases. This wide range in clinical response depends on several biological and clinical variables that allow the selection of patients with the highest probability of successful treatment. These agents are a mainstay in MDS therapy, but many issues are still open in terms of the initiation of therapy, the optimal dosage of erythropoietic stimulating agents (ESAs), the most efficient type of ESA, and the duration and outcome of such treatments. In this review, the mechanisms of response and predictive factors as well as an analysis of the clinical activity of ESAs in MDS therapy are presented.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Myelodysplastic Syndromes; Recombinant Proteins

Management of anaemia in chronic renal insufficiency (CRI) represents an important medico-economic challenge because of the great number of patients and the cost of the erythropoiesis-stimulating agent (ESA). The aim of this study was to identify determinants of the costs associated with these treatments in order to choose, with equal efficacy, the most efficient ASE.. A bibliographic research was realised by Medline database interrogation.. Among the direct medical costs, five studies showed that acquisition of epoetine alfa (EA) compared to darbepoetin alfa (DA) was less expensive. Concerning the costs associated with the route of administration, the subcutaneous injection (SC) of epoetine allowed a gain in costs because of the decrease of doses compared to the intravenous (IV) route. The switch from EA in SC to DA in IV, for hemodialysis patients, was associated with a reduction of the number of injections and with a treatment's cost lower by DA than by EA. Costs related to the regimen of administration, notably those related to nursing, medical and pharmaceutical time, were negligible towards those associated to the acquisition of the ASE. Finally, the costs of the therapeutic follow-up and treatment of the adverse effects of the ASE were similar between the EA and the DA.. The costs associated with the prices of acquisition of the ASE, negotiated by the structure of care, represent the most important part of the direct medical costs.

Topics: Anemia; Darbepoetin alfa; Direct Service Costs; Drug Costs; Epoetin Alfa; Erythropoietin; France; Health Care Costs; Hematinics; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Recombinant Proteins

The triad of diabetes mellitus, anemia, and chronic kidney disease (CKD) define a group of patients at high risk for death and cardiovascular complications. The approval of epoetin alfa in 1989 transformed the treatment of anemia in patients with CKD. However, evidence has emerged from randomized controlled trials that correcting anemia with erythropoiesis-stimulating agents in CKD patients is associated with increased risk. Most recently, the TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy) study of anemic type 2 diabetic patients with CKD reported that treatment with darbepoetin conferred no benefit in mortality or in attenuating cardiovascular or renal events. Instead, there was a twofold higher rate of stroke and thromboembolic complications and a higher rate of cancer deaths in patients randomized to treatment with darbepoetin. Furthermore, there was an inconsistent and modest improvement in health-related quality of life. TREAT raises questions about whether anemia in type 2 diabetic patients should be treated and under what circumstances.

Topics: Anemia; Darbepoetin alfa; Diabetes Mellitus, Type 2; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Recombinant Proteins

epoetin zeta is a recently introduced recombinant erythropoietin, designed to be biologically similar to epoetin alfa. This posthoc analysis evaluated the impact of switching patients with chronic kidney disease (CKD) on hemodialysis from epoetin alfa to epoetin zeta, or vice versa, on hemoglobin concentration, epoetin dose, and patient safety.. data were analyzed from three published trials: two 24-week randomized, double-blind (maintenance and induction) studies and a 56-week, open-label, follow-on study involving adult patients with CKD stage 5, maintained on hemodialysis, and receiving epoetin alfa or epoetin zeta. Patients had either completed and switched treatments within the maintenance study, or had completed the induction or maintenance study on epoetin alfa and then switched to, and completed at least 12 weeks of follow-up treatment on, epoetin zeta. Mean hemoglobin levels and epoetin dose were evaluated pre- (0-4 weeks before) and post- (8-12 weeks after) switch, and were considered equivalent for the two treatments if the upper and lower limits of the 95% confidence intervals (CIs) for the intraindividual differences in mean values fell within accepted limits.. overall, 481 patients were included in the analysis. Mean hemoglobin concentration was maintained at target levels (10.5-12.5 g/dL) throughout the drug switch. The mean differences in hemoglobin concentration and associated 95% CIs following the switch remained within prespecified equivalence limits (± 1.0 g/dL). The 95% CIs of the mean difference in weekly epoetin dose postswitch also remained within prespecified equivalence margins (± 45 IU/kg; upper limit 17.83 IU/kg, lower limit -10.91 IU/kg). Both treatments were similarly well tolerated.. our data suggest that epoetin alfa and epoetin zeta therapy can be interchanged without any clinically significant alteration in efficacy, safety, or epoetin dose, in patients with CKD on dialysis receiving stable epoetin maintenance therapy.

Topics: Adult; Aged; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Therapeutic Equivalency; Young Adult

Epoetin alpha (EPO) continues to be the initial treatment of choice for most anemic patients with myelodysplastic syndromes (MDS). Over the years, different therapeutic strategies have been adopted to optimize the clinical benefits of EPO in this setting.. In the current meta-analysis of published literature, erythroid response (ER) rates with EPO as a single agent versus its combination with granulocyte-colony-stimulating factor (G-CSF) or granulocyte-macrophage-colony-stimulating factor (GM-CSF) were compared.. The assessment indicated that the ER rates were comparable between the 2 EPO-based therapeutic strategies. Furthermore, EPO monotherapy at a higher dose of 60,000 to 80,000 U weekly produced significantly higher ER rates (64.5%) compared with the standard oncology dose of 30,000 to 40,000 U weekly either as a single agent (49%; P < .001) or in combination with G-CSF/GM-CSF (50.6% P = .007). In addition, when transfusion-dependent patients were assessed separately, both EPO monotherapy and its combination with G-CSF/GM-CSF produced comparable and appreciable levels of transfusion independence (28.8% and 24.8%, respectively).. In the current meta-analysis, higher doses of EPO demonstrated better ER rates compared with EPO at standard doses alone or in combination with G-CSF/GM-CSF. Furthermore, the authors concluded that prospective clinical studies are warranted to evaluate the use of higher doses of EPO in anemic patients with MDS.

Topics: Aged; Anemia; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematinics; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Prognosis; Recombinant Proteins

The Standards, Options, and Recommendations (SOR) project undertaken by the French National Federation of Cancer Centers (FNCLCC) to develop and disseminate clinical practice guidelines in oncology has now been taken over by the French National Cancer Institute. In 2007, the SOR updated the information related to the use of erythropoiesis-stimulating agents (ESA) in anemic children with cancer. Updates were based on a review of the most reliable scientific data available, followed by critical appraisal by a multidisciplinary group of experts and validation by independent experts. The literature review identified four randomized trials likely to provide reliable new information on the use of ESA in children. This review confirmed four points: treatment increases hemoglobin levels and decreases the need for blood transfusions; no quality-of-life and no survival benefit has been demonstrated; treatment does not seem associated with significantly more side effects; impact on thromboembolic events and patient quality of life remains unclear. The main result of the study was the elaboration of a new standard of care unavailable at the time of the 2003 version. Systematic administration of ESA is not recommended for the prevention or treatment of anemia in pediatric cancer patients. However, treatment decision must be made on a case-by-case basis and, when treatment is considered, the intravenous route must be preferred. The full French document is available at www.sor-cancer.fr.

Topics: Anemia; Animals; Cell Proliferation; Child; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Intravenous; Neoplasms; Practice Guidelines as Topic; Quality of Life; Receptors, Erythropoietin; Recombinant Proteins; Survival Rate

The treatment of cancer-induced anemia with erythropoietin-stimulating agents (ESAs) is reviewed.. Before the introduction of ESAs, the only treatment option for cancer-related anemia was red blood cell (RBC) transfusion. The use of ESAs in multiple disease states has been well established and is now considered first-line treatment for many forms of anemia. Chang et al. evaluated the effect of epoetin alfa (40,000 units administered subcutaneously every week) and standard-of-care therapy on quality of life (QOL), transfusion requirements, and hemoglobin levels in 354 patients with breast cancer who had a baseline hemoglobin concentration of <15 g/dL. The authors concluded that early initiation of treatment with epoetin alfa in patients with breast cancer is effective in maintaining hemoglobin levels, reducing transfusions, and improving QOL. Leyland-Jones et al. conducted a study evaluating the effects of early intervention with epoetin alfa (40,000 units administered subcutaneously every week) on survival and QOL of mainly nonanemic patients with metastatic breast cancer. In contrast to Chang et al., this study was discontinued because of lower overall survival rates within the epoetin alfa group. In 2008, the Food and Drug Administration issued a black-box warning for both epoetin alfa and darbepoetin alfa. The warning acknowledges that ESAs have shortened overall survival and time to disease progression in patients with advanced breast cancer who are given these agents to achieve a target hemoglobin concentration of > or =12 g/dL.. When used in patients with cancer-induced anemia, ESAs should only be given at the lowest dose possible to prevent RBC transfusions. During treatment, hemoglobin levels should be monitored closely and ESA doses need to be adjusted accordingly.

Topics: Anemia; Blood Transfusion; Breast Neoplasms; Darbepoetin alfa; Drug Labeling; Drug Monitoring; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Rate

Topics: Anemia; Animals; Diabetic Nephropathies; Disease Progression; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Nephrotic Syndrome; Proteinuria; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins

Erythropoiesis-stimulating agents (ESAs) reduce anemia in cancer patients and may improve quality of life, but there are concerns that ESAs might increase mortality.. Our objectives were to examine the effect of ESAs and identify factors that modify the effects of ESAs on overall survival, progression free survival, thromboembolic and cardiovascular events as well as need for transfusions and other important safety and efficacy outcomes in cancer patients.. We searched the Cochrane Library, Medline, Embase and conference proceedings for eligible trials. Manufacturers of ESAs were contacted to identify additional trials.. We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusions (as necessary) versus red blood cell transfusions (as necessary) alone, to prevent or treat anemia in adult or pediatric cancer patients with or without concurrent antineoplastic therapy.. We performed a meta-analysis of randomized controlled trials comparing epoetin alpha, epoetin beta or darbepoetin alpha plus red blood cell transfusions versus transfusion alone, for prophylaxis or therapy of anemia while or after receiving anti-cancer treatment. Patient-level data were obtained and analyzed by independent statisticians at two academic departments, using fixed-effects and random-effects meta-analysis. Analyses were according to the intention-to-treat principle. Primary endpoints were on study mortality and overall survival during the longest available follow-up, regardless of anticancer treatment, and in patients receiving chemotherapy. Tests for interactions were used to identify differences in effects of ESAs on mortality across pre-specified subgroups. The present review reports only the results for the primary endpoint.. A total of 13933 cancer patients from 53 trials were analyzed, 1530 patients died on-study and 4993 overall. ESAs increased on study mortality (combined hazard ratio [cHR] 1.17; 95% CI 1.06-1.30) and worsened overall survival (cHR 1.06; 95% CI 1.00-1.12), with little heterogeneity between trials (I(2) 0%, p=0.87 and I(2) 7.1%, p=0.33, respectively). Thirty-eight trials enrolled 10441 patients receiving chemotherapy. The cHR for on study mortality was 1.10 (95% CI 0.98-1.24) and 1.04; 95% CI 0.97-1.11) for overall survival. There was little evidence for a difference between trials of patients receiving different cancer treatments (P for interaction=0.42).. ESA treatment in cancer patients increased on study mortality and worsened overall survival. For patients undergoing chemotherapy the increase was less pronounced, but an adverse effect could not be excluded.

Topics: Adult; Anemia; Child; Darbepoetin alfa; Disease-Free Survival; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Humans; Male; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

Anemia is the most frequent hematologic abnormality among cancer patients. Its pathophysiology comprises reduction in erythrocyte half-life, poor iron reutilization by the bone marrow, and inadequate response to erythropoietin (EPO), with reduced endogenous EPO (eEPO) levels. Current treatment implies the use of erythropoiesis- stimulating agents (ESA), to which 35-48% of patients show primary resistance. The search for predictors of response to ESA treatment has been inconclusive. Iron or vitamin deficiency, the recent need for transfusion, or a lack of hemoglobin increase within the first 2-4 weeks usually predict resistance to ESA. High serum eEPO levels at treatment initiation (>100-150 mU/ml) may also predict resistance, especially in hematologic malignancies, but the results in solid tumors are not consistent. Although patients with cancer-related anemia show higher eEPO levels than patients without anemia, there is extreme variability among individuals. Future studies are needed to clarify eEPO usefulness in predicting response to ESA treatment.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Humans; Neoplasms; Predictive Value of Tests; Recombinant Proteins

Anemia with consequent tissue hypoxia is common problem in cancer patients. Developed via various patophysiological mechanisms, it has deleterious effect on quality of life and survival of patients with cancer. Recognition of symptoms and timely initiation of treatment improve patients' quality of life, as well as efficacy of oncological treatment. Red blood cells transfusions are well known and efficient way of anemia correction. They are "golden standard" in treatment of cancer-related anemia today, and are unavoidable in almost all patients with hemoglobin concentration below 80 g/L. Newest therapy guidelines in developed countries, supported by recent literature, encourage use of recombinant human erythropoietin (rHu-EPO), although detailed meta-analyses and prospective randomized clinical trials have shown that rHu-EPO decreases the need for transfusions in only 9-45% patients with cancer, only if they have mild anemia, rHu-EPO increases incidence of thromboembolic events, and suspicion arises that it supports tumor cells growth and multiplication. Therefore, it is necessary to define subgroups of patients which are best candidates for rHu-EPO therapy, to accomplish lower intensity of transfusion therapy.

Topics: Anemia; Animals; Blood Transfusion; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Anemia; Critical Illness; Epoetin Alfa; Erythropoietin; Humans; Recombinant Proteins; Treatment Outcome

To update the American Society of Clinical Oncology/American Society of Hematology (ASCO/ASH) recommendations for the use of epoetin. The guideline was expanded to address use of darbepoetin and thromboembolic risk associated with these agents.. An Update Committee ("Committee") reviewed and analyzed data published since 2002 through July 2007. MEDLINE and the Cochrane Collaboration Library databases were searched.. For patients with chemotherapy-associated anemia, the Committee continues to recommend initiating an erythropoiesis-stimulating agent (ESA) as hemoglobin (Hb) approaches, or falls below, 10 g/dL, to increase Hb and decrease transfusions. ESA treatment continues to be recommended for patients with low-risk myelodysplasia for similar reasons. There is no evidence showing increased survival as a result of ESA treatment. Conclusive evidence is lacking that, absent clinical circumstances necessitating earlier treatment, initiating ESAs at Hb levels greater than 10 g/dL either spares more patients from transfusion or substantially improves their quality of life. Starting doses and dose modifications based on response or lack thereof should follow the package insert. Continuing ESAs beyond 6 to 8 weeks in the absence of response, assuming appropriate dose increase has been attempted in nonresponders as per US Food and Drug Administration-approved label, does not seem to be beneficial, and ESA therapy should be discontinued. The Committee recommends monitoring iron stores and supplementing iron intake for ESA-treated patients. ESAs should be used cautiously with chemotherapy, or in clinical states, associated with elevated risk for thromo-embolic complications. The Committee also cautions against ESA use for patients with cancer who are not receiving chemotherapy, since recent trials report increased thromboembolic risks and decreased survival under these circumstances.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Hematology; Humans; Medical Oncology; Neoplasms; Recombinant Proteins; Societies, Medical

The purpose of this paper is to provide an overview of the current therapeutic options afforded to anemic chronic kidney disease (CKD) patients and the costs of these interventions.. Literature search of articles within Ovid MEDLINE between 1996 and 2007 that pertained to the treatment of anemia in chronic kidney disease patients.. Early detection and treatment of anemia associated with CKD has proven to provide positive cognitive and physical effects. Treatment options that increase iron storage and availability within the body and production of erythropoietin can assist in anemic CKD patients in achieving recommended levels of hemoglobin. Acknowledgement of the potential side effects associated with the medications selected to treat anemia can help in avoiding additional injury to the patient and thus reduce healthcare expenditure. A limitation of this review is that the search was performed within a single database.. Health care providers can play an active role in detecting anemia early and optimizing available treatment options. Future research on the effects of erythropoiesis-stimulating agents (ESA) on patients before they need dialysis, and a cost analysis between epoetin and darbepoetin alpha, would be beneficial.

Topics: Anemia; Darbepoetin alfa; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Health Care Costs; Hematinics; Humans; Iron; Practice Guidelines as Topic; Recombinant Proteins; Renal Insufficiency, Chronic

Topics: Anemia; Biological Products; Epoetin Alfa; Erythropoietin; European Union; Hematinics; Humans; Recombinant Proteins; Therapeutic Equivalency

Anemia in children with cancer is not an uncommon complication and is usually multifactorial in etiology. In numerous trials in adult cancer patients, treatment with recombinant erythropoietin has been shown to increase hemoglobin levels, reduce red blood cell transfusion requirements, and improve quality of life. Much less has been published of its use in the prevention or treatment of cancer-associated anemia (CAA) in children, in whom chemotherapy is usually more intensive and likely to result in greater myelosuppression. This review critically evaluates the published evidence of its use in childhood cancer especially; its safety and efficacy in the prevention and treatment of CAA and some indications for its use in childhood cancer are suggested.

Topics: Age Factors; Anemia; Child; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Evidence regarding the cost-effective use of and benefits associated with epoetin alfa in treating anemia of critically ill patients is assessed.. Anemia of critical illness is a leading cause of inadequate oxygen delivery that affects almost all patients in the intensive care unit setting after day 3. Red blood cell transfusions are commonly used to correct anemia of critical illness, but they are also associated with risks including hemolytic reactions and viral transmission. The latest evidence suggests that when a strict transfusion protocol is implemented, epoetin alfa does not decrease the transfusion requirements of critically ill patients. In the absence of a strict transfusion protocol, an average of 5.1 doses of epoetin, at a cost of $2154, is required to avoid one transfusion. Evidence is accumulating that epoetin may reduce mortality rates in trauma patients. However, important questions remain regarding the magnitude and mechanism of the potential benefit and if the benefit outweighs the risk of thromboembolism. Therefore, the reduction in transfusion-related adverse events is the only clinical outcome benefit that is well-supported by current evidence. However, the known risk of transfusion-related adverse events is low; approximately 29,000 patients would need to be treated to avoid a serious transfusion-related event. Treating these patients would cost over $25 million, and it would take over 100 years to prevent one serious event in a unit admitting 20 epoetin-eligible patients per month.. Published data suggest a prohibitive cost associated with epoetin alfa use in critically ill patients given that the only well-supported clinical benefit of this treatment is the avoidance of transfusion-related adverse events. Continued research is necessary to clarify if there is a net clinical benefit of epoetin use (especially in trauma patients) and to develop optimal blood management strategies.

Topics: Anemia; Cost-Benefit Analysis; Critical Care; Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Intensive Care Units; Oxygen; Randomized Controlled Trials as Topic; Recombinant Proteins; Thromboembolism

Several studies with erythropoiesis-stimulating agents (ESAs) have raised a number of safety issues. Therefore, a discussion of available data in light of the current EORTC guidelines 2006 on the use of ESAs in anemic patients is warranted.. Literature is reviewed with respect to experimental and clinical data on the effect of ESA therapy on tumor growth both in the preclinical setting and on patient survival.. Studies showing an adverse effect of ESA therapy on patient survival generally exhibit considerable methodological deficiencies. Moreover, they investigated treatment situations for which ESAs are not approved and/or did not involve recommended baseline ("intervention") or target hemoglobin levels.. When used as indicated, ESAs are valuable and safe drugs for the treatment of anemia and do not negatively affect patient survival. In particular, the data situation confirms the importance and correctness of the EORTC guidelines 2006 and their recently updated version. It is therefore recommended that these guidelines continue to be strictly followed in the treatment of chemotherapy-induced anemia.

Topics: Adult; Anemia; Animals; Antineoplastic Agents; Blood Transfusion; Clinical Trials as Topic; Clinical Trials, Phase II as Topic; Disease Models, Animal; Disease Progression; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Meta-Analysis as Topic; Mice; Neoplasms; Neoplasms, Experimental; Oxygen; Practice Guidelines as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Rats; Receptors, Erythropoietin; Recombinant Proteins; Risk Factors; Safety; Tumor Cells, Cultured

To discuss the clinical issues we addressed in the development of our institutional guidelines regarding the assessment of iron stores for cancer- and treatment-related anemia and the administration of parenteral iron with erythropoiesis-stimulating agents (ESAs).. Studies published from January 1995 to August 2007 were identified by computer searches of Medline and hand searching of bibliographies of the articles identified via the computer searches. The current clinical practice guidelines were identified by computer searches of the web sites for national professional organizations that represent health care professionals who treat patients with cancer.. of data analysis. Hematopoietic responses demonstrate that epoetin alfa and darbepoetin alfa provide similar outcomes for patients with chemotherapy-induced anemia (CIA); however, up to 50% of patients receiving these agents fail to adequately respond. Functional iron deficiency defined as a state of iron-restricted erythropoiesis is likely the primary contributor to the lack of response. Hematopoietic responses following ESA therapy with parenteral iron are substantially higher compared to response with no or oral iron.. Iron stores should be assessed in all patients with cancer- or treatment-related anemia and parenteral iron should be administered to patients receiving ESA therapy to improve hematopoietic response. A unique algorithm that summarizes our institutional guidelines to assess iron stores and administer parenteral iron with ESA therapy in patients with CIA is included.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Therapy, Combination; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Humans; Injections, Intravenous; Iron Compounds; Practice Guidelines as Topic; Recombinant Proteins

The present meta-analysis was undertaken to (1) assess erythroid response rates in myelodysplastic syndromes (MDS) patients treated with epoetin alfa as a monotherapy, (2) gain further insights into predictors of response rates, and (3) compare the erythroid response rates observed with epoetin alfa and darbepoetin alfa. A systematic review of studies from 1990 to 2006 in MDS patients treated with epoetin alfa or darbepoetin alfa was performed and yielded 30 studies evaluating a total of 1,314 patients (epoetin alfa: 22 studies, 925 patients; darbepoetin alfa: eight studies, 389 patients). Pooled estimates of erythroid response rates, stratified by the International Working Group criteria (IWGc) and treatment group, were calculated using random-effects meta-analysis methods. Univariate meta-regression analyses were further conducted to identify study characteristics associated with erythroid response rate. The pooled estimate of erythroid response rate was significantly higher for epoetin alfa IWGc studies (57.6%) as compared to non-IWGc studies (31.6%; p < 0.001). Study factors predictive of higher response rate in the epoetin alfa IWGc studies included higher proportion of patients with RA/RARS (p < 0.001), lower mean baseline serum erythropoietin level (p = 0.007), and fixed dosing regimen (p < 0.001). There was no significant difference in the pooled erythroid response rates between the two agents (epoetin alfa: 57.6% vs. darbepoetin alfa: 59.4%; p = 0.828). The current study reported significantly higher erythroid response rates predominantly in the more recent studies that primarily utilized IWGc to define response. With the use of standardized patient selection and response evaluation methods, epoetin alfa and darbepoetin alfa yielded comparable erythroid response rates in MDS patients.

Topics: Aged; Anemia; Anemia, Refractory; Anemia, Sideroblastic; Blood Transfusion; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Evaluation; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Male; Myelodysplastic Syndromes; Recombinant Proteins; Treatment Outcome

The biology of iron in relation to anemia is best understood by a review of the iron cycle, since the majority of iron for erythropoiesis is provided by iron recovered from senescent erythrocytes. In iron-deficiency anemia, storage iron declines until iron delivery to the bone marrow is insufficient for erythropoiesis. This can be monitored with clinical indicators, beginning with low plasma ferritin, followed by decreased plasma iron and transferrin saturation, and culminating in red blood cells with low-Hb content. When adequate dietary iron is provided, these markers show return to normal, indicating a response to the dietary supplement. Anemia of inflammation (also known as anemia of chronic disease, or ACD) follows a different course, because in this form of anemia storage iron is often abundant but not available for erythropoiesis. The diagnosis of ACD is more difficult than the diagnosis of iron-deficiency anemia, and often the first identified symptom is the failure to show a response to a dietary iron supplement. Confirmation of ACD is best obtained from elevated markers of inflammation. The treatment of ACD, which typically employs erythropoietin (EPO) supplements and intravenous iron (i.v.-iron), is empirical and often falls shorts of therapeutic goals. Dialysis patients show a complex pattern of anemia, which results from inadequate EPO production by the kidney, inflammation, changes in nutrition, and blood losses during treatment. EPO and i.v.-iron are the mainstays of treatment. Patients with heart failure can be anemic, with incidence as high as 50%. The causes are multifactorial; inflammation now appears to be the primary cause of this form of anemia, with contributions from increased plasma volume, effects of drug therapy, and other complications of heart disease. Discerning the mechanisms of anemia for the heart failure patient may aid rational therapy in each case.

Topics: Anemia; Anemia, Iron-Deficiency; Chronic Disease; Epoetin Alfa; Erythropoietin; Female; Heart Diseases; Hematinics; Humans; Inflammation; Iron; Kidney Diseases; Male; Recombinant Proteins

After almost 20 years, anemia in chronic kidney disease (CKD) and its treatment remain the focus of multiple questions for clinicians and investigators. The optimal hemoglobin (Hb) for patients with CKD is controversial and different targets are probably required for different populations. The current literature does not support an upper Hb target >12 g/dl and there is a clear demonstration of increased risk with Hb targets >13 g/dl. With this narrow target of 11-12 g/dl, fluctuations in Hb concentration are commonly observed in patients being treated with erythropoiesis-stimulating agents (ESAs). Studies to date provide a suggestion of an association between Hb cycling and mortality, but they have been primarily exploratory in nature and clinical trials comparing treatment strategies leading to different degrees of Hb variability are needed. The great majority of incidences of pure red cell aplasia (PRCA) was associated with ESA therapy and was first recognized several years ago after a change in the formulation in which human serum albumin was eliminated and replaced by polysorbate-80 in patients on epoetin alfa (Eprex). Years later, a registry (PRIMS) was established by the health authorities as part of a reapproval of the subcutaneous route to confirm that the cause of PRCA has been eliminated. The ongoing PRIMS study is a 3-year observation period prospective multicenter and international (Europe and Australia) registry that could serve as a model for assessment of the immunogenicity profiles of currently marketed and future ESAs. The association with a change in formulation makes PRCA of interest to the biotechnology industry as well as the medical community because it raises the broader question of the potential immunogenicity of biopharmaceuticals in general.

Topics: Anemia; Chronic Disease; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Kidney Diseases; Recombinant Proteins; Red-Cell Aplasia, Pure

Since 1988, millions of patients have received epoetin products intravenously (IV) and subcutaneously. In 1998, epoetin-associated pure red cell aplasia (PRCA) was first reported and causation was attributed to formulations without human serum albumin (HSA), subcutaneous administration, and uncoated rubber stoppers.. Data on erythropoietin (EPO)-associated PRCA were obtained from the Food and Drug Administration (FDA), regulatory authorities in other countries, and the manufacturers of epoetin alfa, epoetin beta, and darbepoetin. The data included information on numbers of PRCA cases and estimated exposure-adjusted incidence rates by EPO product, anemia etiology, administration route, country of PRCA identification, and date reported.. In 1999, academicians in Paris identified 12 EPO-treated patients with antibody-mediated PRCA; 11 of these patients were on hemodialysis and had received subcutaneous Eprex (Johnson & Johnson). In 2002, authorities in Europe, Australia, Singapore, and Canada mandated Eprex by IV route to hemodialysis patients, and the relevant manufacturers added Teflon coating to prefilled syringes of Eprex; PRCA cases subsequently decreased by 90 percent. By 2003, 180 Eprex-associated PRCA cases were identified in Europe, Canada, Australia, and Asia, despite improvements in handling. Since 2002, FDA safety databases include information on 59 new cases of antibody-associated PRCA, primarily associated with subcutaneous epoetin alfa and darbepoetin that does not contain HSA.. Independent actions by regulatory authorities, manufacturers, and academic researchers identified significant numbers of PRCA cases between 1998 and 2003 and characterized the probable etiology. Today, antibody-mediated PRCA is an infrequent class toxicity occurring among some hemodialysis patients on EPOs.

Topics: Anemia; Drug Labeling; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins; Red-Cell Aplasia, Pure

Beginning 1998, a working group of specialists convened by the guidelines department (Standards, Options and Recommendations: SOR) of the National French Federation of Comprehensive Cancer Centres (FNCLCC) published then regularly updated Recommendations relative to the use of ESA in anaemic patients with cancer. This article presents a short version of the Recommendations updated in 2007.. This updating process is based on the methodology developed and used in the "Standards, Options: Recommendations" programme. The methodological approach combines systematic review with the judgement of a multidisciplinary group of experts. A Recommendation is a proposal of one or several clinical attitudes intended to improve cancer patient care. There are two levels of gradation for the Recommendations: Standards and Options. Their setting takes into account the organisational context of care, the particular situation of the patient and the expression of his preferences. Before publication, the RPC-SOR are re-examined by independent reviewers selected according to the same principles as the group of expert writers.. New data are sufficiently important to update the latest Recommendations validated in 2003. Thus, five clinical questions were updated. The resulting modifications were either major (new Options or new Standards) or minor (increased level of evidence). It should be noted that for the clinical question--use of ESA in radiotherapy--new data are not sufficient to generate modifications in the initial Recommendations which remain valid.. Because of the important new data published on the subject between 2003 and 2007, it appears relevant to re-examine these Recommendations according to a systematic monitoring process which should be renewed in 2 years.

Topics: Adult; Anemia; Child; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; France; Hematinics; Humans; Iron Compounds; Neoplasms; Recombinant Proteins

Recombinant human erythropoietin has been used for more than 20 years for the treatment of renal anaemia, with epoetin-alfa and -beta representing the common traditional preparations. By the modification of the molecule's carbohydrate moiety or structure a longer duration of erythropoietin receptor stimulation was achieved. The administration of these new molecules (darbepoetin, C.E.R.A.) once or twice a month is also sufficient to achieve serum haemoglobin target levels, making the treatment safer and more comfortable both for the patients and the personnel. These recently developed synthetic erythropoietin receptor stimulating molecules, along with recombinant human erythropoietin, are together called "Erythropoiesis Stimulating Agents". In haemodialysed patients the intravenous route is preferred, but the subcutaneous administration can substantially reduce dose requirements. In praedialysed, transplanted or peritoneally dialysed patients, erythropoiesis stimulating agents should preferably be given subcutaneously both for economic and practical reasons. There are ongoing clinical trials with erythropoiesis stimulating molecules that can be administered by inhalation or per os. Current evidence suggests that the serum haemoglobin level should preferably not exceed 12 g/dl with the use of erythropoiesis stimulating agents. No cardiovascular protective effect of higher serum haemoglobin levels was demonstrated in two large clinical trials. Further well-designed studies are necessary to set evidence-based haemoglobin targets for erythropoiesis stimulating treatment. Arguments for a more widespread use of agents with extended duration include medical, financial and patient satisfaction reasons. The release of new erythropoiesis stimulating agents may further simplify the treatment of renal anaemia.

Topics: Administration, Cutaneous; Administration, Inhalation; Administration, Oral; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Heart Failure; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Infusions, Intravenous; Kidney Failure, Chronic; Receptors, Erythropoietin; Recombinant Proteins; Renal Dialysis

The elements and limitations of pharmacoeconomic models, types of analytic methods used in pharmacoeconomic evaluations, outcomes used in studies of anemia treatments, and comparative efficacy and cost-effectiveness of the two available erythropoietic therapies in the treatment of anemia in cancer and critical care patients are discussed.. Clinical, humanistic, and economic outcomes should be taken into consideration in pharmacoeconomic models. The validity of such models may be compromised by a lack of outcome data, unreasonable assumptions, the heterogeneity of the patient population, patient selection bias in comparative studies, and inconsistent use of instruments to measure outcomes. The degree of anemia in patients with cancer correlates with health-related quality of life (QOL). Erythropoietic therapy increases hemoglobin concentrations and QOL, reduces the need for blood transfusions, and is cost-effective for treating anemia in cancer and critical care patients. Epoetin alfa may provide a more rapid hemoglobin response and improvement in QOL at a lower cost than darbepoetin alfa. Front loading with weekly doses of either erythropoietic agent followed by a three-week-long dosing interval for maintenance treatment may be used to quickly correct anemia, improve convenience, and reduce costs.. Erythropoietic therapy for the treatment of anemia in cancer and critical care patients is cost-effective.

Topics: Anemia; Cost-Benefit Analysis; Critical Care; Critical Illness; Darbepoetin alfa; Economics, Pharmaceutical; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Patients with cancer-related anaemia generally have a poor prognosis. Evidence suggests that an effective erythropoietic protein (epoetin)-mediated haemoglobin (Hb) response provides marked improvement in quality of life (QoL). An early Hb response to erythropoietic protein therapy in these patients would appear ideal but few studies have compared the speed of response to different erythropoietic proteins, or the potential benefits associated with an early Hb response.. The pharmacokinetic/pharmacodynamic profiles of commercially available erythropoietic proteins are reviewed along with available clinical data to examine Hb response and associated clinical outcomes for each of these agents. Randomised, head-to-head trials comparing epoetin alfa and darbepoetin alfa suggest that patients administered with epoetin alfa achieve a satisfactory Hb response significantly earlier than those given darbepoetin alfa, and with consistently lower monthly transfusion rates. Non-comparative studies support this, suggesting also that epoetin beta may provide a relatively faster Hb response in a greater number of patients than either epoetin alfa or darbepoetin alfa, irrespective of malignancy or chemotherapy type. Moreover, studies suggest consistently that a 'front-loading' dosing regimen with epoetin alfa does not convey improved speed of Hb response over epoetin beta administered according to current clinical practice guidelines.. Given the poor prognosis of anaemic patients with cancer, the use of an agent which provides clinical benefits quickly but with minimal thromboembolic risk, should be considered an essential component of anaemia management in these patients. However, more head-to-head studies are required to confirm the relative efficacy of currently available erythropoietic proteins.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Neoplasms; Quality-Adjusted Life Years; Recombinant Proteins; Retrospective Studies; Thromboembolism; Treatment Outcome

Patients with lymphoid malignancies frequently require repetitive and intensive anticancer treatments to induce and maintain disease remission. Anaemia (haemoglobin [Hb] <12 g/dL) is a common and debilitating problem associated with both the malignancy itself and its treatment burden. Anaemia negatively impacts on all aspects of patient quality of life (QOL) and treatment outcomes and survival, particularly in this disease setting. Widely acknowledged goals of anaemia treatment include Hb correction to approximately 12 g/dL, reduction in transfusion requirements and optimisation of patient QOL. Since the introduction of recombinant human erythropoietic therapy, transfusion (once the only anaemia treatment option available) is now primarily reserved for non-responders or those with severe or life-threatening anaemia. Data from randomised, double-blind, placebo-controlled studies, and large, non-randomised, open-label, community-based studies, along with almost 15 years of practical experience, support the assertion that epoetin alfa administered at a dosage of 150-300 U/kg three times weekly or 40,000-60,000U once weekly, both of which are US FDA-approved dose administration schedules, can effectively and safely achieve anaemia treatment goals for the majority of patients with lymphoid malignancies. Data and practical experience collected over the last 5 years on another erythropoietic agent with a slightly longer half-life but lower binding affinity, darbepoetin alfa, show that this agent when administered according to the FDA-approved dose administration schedules (2.25-4.5 microg/kg once weekly or 500microg once every 3 weeks) or according to a commonly-administered dose in clinical practice (3.0-5.0 microg/kg once every 2 weeks) can also effectively and safely correct anaemia, reduce transfusion requirements and improve QOL in many patients with lymphoid malignancies. One comparative head-to-head trial suggested that epoetin alfa might be superior to darbepoetin alfa in anaemic cancer patients receiving chemotherapy with respect to timing and magnitude of Hb correction, although further study is necessary, especially concerning optimal dose administration. Alternative dose administration schedules, such as epoetin alfa 80,000U every 2 weeks from initiation or 80,000U every 3 weeks following initiation with once weekly administration and darbepoetin alfa 4.5 microg/kg every 3 weeks following initiation with once weekly administration, are being actively

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Combined Modality Therapy; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Iron; Lymphoma; Practice Guidelines as Topic; Quality of Life; Recombinant Proteins; Trace Elements

Healthcare organizations must evaluate the cost effectiveness of the alternative therapies that are available to treat anemia and improve quality of life (QoL) of patients with cancer, that is, erythropoietic protein therapy and blood transfusion.. Pharmacoeconomic studies that evaluated the cost of not treating anemia or treating with transfusion or erythropoietic protein therapy were reviewed and compared. Studies of individual erythropoietic proteins (epoetin alfa, epoetin beta or darbepoetin alfa) were also assessed. As no prospective trials have compared the erythropoietic proteins, retrospective studies and the results of separate trials were analyzed. The database searched for this review was PubMed (open date to August 2006). Recent conference abstracts were also searched (2003-July 2006).. There is a high cost associated with anemia in cancer patients. Treatment of anemia is likely to lead to increased hemoglobin (Hb) levels and improved QoL as principal outcomes. Therefore, in assessing erythropoietic protein versus transfusion, it is more appropriate to use Hb or QoL as endpoint rather than quality adjusted life year. Studies with the former approach showed that erythropoietic protein therapy is more cost effective than transfusion. Also, its cost effectiveness should be improved with the use of evidence-based guidelines for patient selection and more tailored utilization. Increasing evidence suggests there might be differences among the erythropoietic proteins in terms of response rate, speed of response, and need for dose escalation.. Significant costs are incurred when anemia in cancer is not treated. Erythropoietic protein therapy is more cost effective than blood transfusion for the treatment of cancer-related anemia. Transfusion should be reserved for patients with poor responses to erythropoietic protein or for the emergency setting, when rapid improvement in Hb is required.

Topics: Absenteeism; Anemia; Blood Transfusion; Budgets; Cost-Benefit Analysis; Darbepoetin alfa; Drug Costs; Epoetin Alfa; Erythropoietin; Health Care Costs; Hemoglobins; Humans; Iron; Neoplasms; Quality of Life; Quality-Adjusted Life Years; Recombinant Proteins; Treatment Outcome

To review the hematologic adverse effects of hepatitis C virus (HCV) therapy and adjuvant treatment with epoetin alfa and granulocyte colony-stimulating factor (ie, filgrastim).. Medical literature indexed in MEDLINE (1966-January 2007) and EMBASE (1980-January 2007) was searched, and published conference abstracts were reviewed.. Peer-reviewed articles and relevant conference abstracts regarding the use of epoetin alfa and granulocyte colony-stimulating factor were reviewed.. Ribavirin induces a dose-dependent hemolytic anemia. Studies using epoetin alfa 40 000 units subcutaneously once weekly have demonstrated efficacy in maintaining hemoglobin, ribavirin dose, and quality of life scores, but clear benefit shown with sustained virologic response (SVR) is lacking. The hemoglobin threshold for initiation of epoetin alfa used in studies may not adequately reflect values used in clinical practice. Treatment-related neutropenia is caused primarily by interferon or peginterferon. Few studies have investigated the impact of granulocyte or granulocyte-macrophage colony-stimulating factor derivatives on neutropenia. Results of dose maintenance evaluation vary, and studies reporting data on SVR showed no effect from growth factor therapy. The frequency of bacterial infections was not reported.. The role and benefit of hematopoietic growth factors in HCV therapy have not been conclusively determined to date. However, the possibility of a benefit to individual patients seen on an outpatient basis remains, and an individualized treatment approach is recommended.

Topics: Anemia; Chemotherapy, Adjuvant; Epoetin Alfa; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Hepatitis C; Humans; Interferons; MEDLINE; Neutropenia; Recombinant Proteins; Ribavirin

Anemia is common in patients with cancer or myelodysplastic syndrome. Erythropoietic therapy offers an effective way to manage anemia by increasing hemoglobin levels, decreasing transfusion requirements, and alleviating symptoms. We reviewed data showing the feasibility and effectiveness of treatment with the erythropoiesis-stimulating protein darbepoetin alfa at extended dosing intervals to treat anemia in patients with cancer receiving multicycle chemotherapy. We also explored the darbepoetin alfa's potential for treating anemia in patients with myelodysplastic syndrome. Data from clinical studies and drug therapy evaluations confirm that darbepoetin alfa administered weekly, every 2 weeks, and every 3 weeks corrects and maintains hemoglobin levels in patients with chemotherapy-induced anemia. In addition, the data demonstrate that both weight-based and fixed dosing with darbepoetin alfa are effective, and that early intervention to treat anemia has clinical benefits. Darbepoetin alfa also is an effective treatment for anemia in patients with cancer not receiving chemotherapy, at extended dosing intervals of at least 3 weeks. Extended dosing for anemia treatment can provide benefits for patients, caregivers, and clinicians because it reduces the number of clinic visits needed and permits synchronizing anemia treatment with chemotherapy cycles. Data from recent studies suggest that darbepoetin alfa is effective for treating anemia in patients with myelodysplastic syndrome; this potential use is being investigated further in ongoing studies. Thus, darbepoetin alfa is an attractive therapy option for patients with chemotherapy or cancer-induced anemia. It allows increased flexibility and simplified dosing and may offer some benefit in the treatment of anemia in patients with myelodysplastic syndrome.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Humans; Myelodysplastic Syndromes; Neoplasms; Recombinant Proteins

To assess the effectiveness and cost-effectiveness of epoetin alpha, epoetin beta and darbepoetin alpha (referred to collectively in this report as epo) in anaemia associated with cancer, especially that attributable to cancer treatment.. Electronic databases were searched from 2000 (1996 in the case of darbepoetin alpha) to September 2004.. Using a recently published Cochrane review as the starting point, a systematic review of recent randomised controlled trials (RCTs) comparing epo with best standard was conducted. Inclusion, quality assessment and data abstraction were undertaken in duplicate. Where possible, meta-analysis was employed. The economic assessment consisted of a systematic review of past economic evaluations, an assessment of economic models submitted by the manufacturers of the three epo agents and development of a new individual sampling model (the Birmingham epo model).. In total 46 RCTs were included within this systematic review, 27 of which had been included in the Cochrane systematic review. All 46 trials compared epo plus supportive care for anaemia (including transfusions), with supportive care for anaemia (including transfusions), alone. Haematological response (defined as an improvement by 2 g/dl(-1)) had a relative risk of 3.4 [95% confidence interval (CI) 3.0 to 3.8, 22 RCTs] with a response rate for epo of 53%. The trial duration was most commonly 16-20 weeks. There was little statistical heterogeneity in the estimate of haematological response, and there were no important differences between the subgroups examined. Haemoglobin (Hb) change showed a weighted mean difference of 1.63 g/dl(-1) (95% CI 1.46 to 1.80) in favour of epo. Treatment with erythropoietin in patients with cancer-induced anaemia reduces the number of patients who receive a red blood cell transfusion (RBCT) by an estimated 18%. Health-related quality of life (HRQoL) data were analysed using vote counting and qualitative assessment and a positive effect was observed in favour of an improved HRQoL for patients on epo. Published information on side-effects was of poor quality. New trials provided further evidence of side-effects with epo, particularly thrombic events, but it is still unclear whether these could be accounted for by chance alone. The results of the previous Cochrane review had suggested a survival advantage for epo (HR 0.84, 95% CI 0.69 to 1.02), based on 19 RCTs. The update, based on 28 RCTs, suggests no difference (HR 1.03, 95% CI 0.88 to 1.21). Subgroup analysis suggested some explanations for this heterogeneity, but it is difficult to draw firm conclusions without access to the substantial amounts of missing or unpublished data, or more detailed results from some of the trials with heterogeneous patient populations. The conclusions are, however, broadly in line with those of a Food and Drug Administration (FDA) safety briefing, which recommended that patients with a haemoglobin above 12 g/dl(-1) should not be treated; the target rate of rise in Hb should not be too great, and further carefully conducted trials are required to determine which subgroups of patients may be harmed by the use of these products, in particular through the stimulation of tumour activity. Five published economic evaluations identified from the literature had inconsistent results, with estimates ranging from a cost per quality-adjusted life-year (QALY) u. Epo is effective in improving haematological response and reducing RBCT requirements, and appears to have a positive effect on HRQoL. The incidence of side-effects and effects on survival remains highly uncertain. However, if there is no impact on survival, it seems highly unlikely that epo would be considered a cost-effective use of healthcare resources. The main target for further research should be improving estimates of impact on survival, initially through more detailed secondary research, such as the individual patient data meta-analysis started by the Cochrane group. Further trials may be required, and have been recommended by the FDA, although many trials are in progress, completed but unreported or awaiting mature follow-up. The Birmingham epo model developed as part of this project contains new features that improve its flexibility in exploring different scenarios; further refinement and validation would therefore be of assistance. Finally, further research to resolve uncertainty about other parameters, particularly quality of life, adverse events, and the rate of normalisation, would also be beneficial.

Topics: Anemia; Antineoplastic Agents; Cost-Benefit Analysis; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Analysis; Treatment Outcome

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Multicenter Studies as Topic; Patient Dropouts; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design

Two independent reviewers used the methodological criteria published by the ISPOR Task Force on Retrospective Data to assess the quality of four posters presenting the results of retrospective database studies on the use of erythropoiesis-stimulating agents (epoetin alfa, epoetin beta, or darbepoetin alfa) for treating patients with cancer. A third reviewer consolidated the results. Overall, from the information reported in the four posters, their methodological quality ranged from poor to very poor; only a few of the criteria were satisfactorily addressed. The quality of the data sources and the research design received very poor scores. Key elements such as selection bias were not considered. These findings caution against the use of posters without appropriate assessment of their methodological quality. The ISPOR guidelines for the evaluation of retrospective analyses are a useful tool for assessing the quality of scientific posters.

Topics: Anemia; Antineoplastic Agents; Benchmarking; Darbepoetin alfa; Data Interpretation, Statistical; Epoetin Alfa; Erythropoietin; Guidelines as Topic; Hematinics; Humans; Neoplasms; Recombinant Proteins; Research Design; Technology Assessment, Biomedical

The recombinant human erythropoietins epoetins alfa and beta have relatively short half-lives ( approximately 24 h by subcutaneous route) and have traditionally been administered 2 or 3 times a week for the treatment of anaemia in patients with chronic kidney disease. However, multiple weekly injections are inconvenient for both the patient and the healthcare provider. With the introduction of the longer-acting erythropoiesis-stimulating agent darbepoetin alfa, there has been growing interest in longer dosing intervals for erythropoiesis-stimulating agents. Data from several randomized studies have shown that darbepoetin alfa is effective in maintaining haemoglobin levels when administered (subcutaneously, intravenously or both) every 2 weeks in dialysis patients, and every 2 weeks or monthly in patients with chronic kidney disease not yet receiving dialysis. Moreover, intravenous administration with darbepoetin alfa does not require a higher dosage compared with the subcutaneous route. Epoetins alfa and beta have also been studied in similar schedules, although few data from well-designed studies are available. Current data suggest that once-weekly administration of these forms of epoetin is feasible in dialysis patients, but dose increases are often required when switching patients from traditional twice- or thrice-weekly schedules. Also, administration of epoetins every other week is feasible in selected patients with chronic renal insufficiency. Further study is required to clarify the optimum schedule for epoetins in these settings.

Topics: Anemia; Chronic Disease; Clinical Trials as Topic; Economics, Pharmaceutical; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Diseases; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

Barriers to the treatment of anemia in patients with chronic kidney disease (CKD), the role of pharmacists in screening patients for anemia and developing guidelines for the use of anemia therapies in patients with CKD, the goals of and considerations in developing pharmacist-managed anemia management clinics, and the potential benefits of these clinics are described.. The complexity of patients with CKD, patient nonadherence to the treatment regimen, a shortage of nephrologists, and a lack of familiarity with clinical practice guidelines and recommendations for treating anemia in these patients are possible barriers to the treatment of anemia. Pharmacists can play a role in improving the treatment of anemia in patients with CKD by screening for anemia, developing guidelines for the use of anemia therapies, and providing patient education to promote adherence to the treatment regimen. The optimal upper limit for hemoglobin concentration during treatment with erythropoietin-stimulating agents (ESA) in patients with CKD remains to be determined, but it should not routinely exceed 13.0 g/dL. Extended dosing of darbepoetin alfa and the new agent continuous erythropoiesis receptor activator appears effective. Iron status often is not assessed in patients with CKD because of difficulty interpreting iron laboratory values and identifying iron deficiency. The usefulness of iron supplementation is not limited to patients with iron deficiency. The intravenous (i.v.) or oral route of administration may be used for iron supplementation in predialysis patients and peritoneal dialysis patients, but the i.v. route is recommended for hemodialysis patients. Adverse effects and drug interactions limit the use of oral iron supplements. Administration of parenteral iron is time consuming and accompanied by concerns about iron accumulation and uncertainty about the optimal maximum serum ferritin concentration. Improved access to care and clinical outcomes and reduced costs have been documented in pharmacist-managed anemia management clinics.. Pharmacists can help overcome barriers to treating anemia in patients with CKD. Clinical and economic benefits are associated with pharmacist-managed anemia management clinics.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Pharmaceutical Services; Polyethylene Glycols; Recombinant Proteins

The prevalence of chronic kidney disease (CKD) and anemia in the United States, classification scheme for CKD, definition of anemia, etiology and consequences of anemia in patients with CKD, and the clinical and economic benefits of correcting anemia are described.. Approximately 20 million people in the United States population have CKD, and 2-4 million of these may also have anemia, which often goes undetected and untreated. Patients with CKD are now classified into five stages based on the degree of kidney function impairment. Here, anemia is caused by insufficient erythropoietin production, and may occur as early as stage 3 CKD. Potential consequences of anemia include cognitive impairment, angina, and the cardiorenal anemia syndrome, a triad of worsening anemia, worsening CKD, and worsening congestive heart failure. Treatment of anemia in predialysis patients with stage 2-4 CKD may slow renal disease progression and improve energy, work capacity, health-related quality of life, and cardiac function. Optimizing the hemoglobin or hematocrit value before initiating dialysis may reduce mortality. Anemia contributes to significant healthcare costs associated with CKD. Substitution of the subcutaneous route of administration for the intravenous route of administration for epoetin alfa can reduce drug acquisition and healthcare costs, the two largest components of healthcare costs in CKD patients. Efforts to slow the progression of CKD could also have a substantial impact on hospitalizations and costs.. Correcting anemia has the potential to improve clinical and economic outcomes in patients with CKD.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Prevalence; Quality of Life; Recombinant Proteins; Renal Dialysis; United States

To compare real-world dosing patterns, drug costs, and hematologic outcome in anemic chronic kidney disease (CKD) patients, not receiving dialysis, who switched from darbepoetin alfa (DARB) to epoetin alfa (EPO) in a community practice setting.. This retrospective observational chart review from a US nephrology clinic included 153 anemic CKD patients > or = 18 years of age who did not receive dialysis during the study period, switched from DARB to EPO between 8/2003 and 8/2005, and received > or = 2 doses of both agents. Paired t-test and McNemar's chi-square were performed comparing pre-switch and post-switch outcomes.. Mean interval between doses increased from 24.3 +/- 11.1 days with DARB to 28.8 +/- 19.8 days with EPO (p = 0.001). Weighted mean pre-switch weekly dose for DARB was 25 mug, while weighted mean post-switch weekly dose for EPO was 7090 Units, resulting in a dose ratio (Units EPO:microg DARB) of 287:1. These doses resulted in mean weekly costs of $110 (DARB) and $86 (EPO). Mean hemoglobin (Hb) levels increased over time from 10.8 g/dL at 6 months pre-switch to 11.1 g/dL 6 months after EPO initiation (p = 0.0132). Mean Hb levels were > 11 g/dL, but below 12 g/dL, while patients received EPO.. Patients switching from DARB to EPO had a greater mean interval between doses, lower drug costs, and consistently maintained recommended Hb levels over time.. The reverse direction (EPO to DARB) was not investigated. Although treatment outcomes were not assessed in a randomized, controlled setting, the study's observational nature provided actual evidence in a real-world setting.

Topics: Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Drug Administration Schedule; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Treatment Outcome

The practice of blood conservation is aimed at improving patient outcomes by avoiding allogeneic transfusions via a coordinated multidisciplinary, multipronged approach. The numerous blood conservation techniques and transfusion alternatives now available are described.. Ongoing concerns exist regarding the availability of the nation's and the world's blood supply. In addition, the number of measures required to ensure blood safety has led to increases in the price of blood and blood products over the past 10-15 years. Moreover, blood transfusion carries inherent risks even under the most favorable circumstances. Investigations have established that injudicious transfusion is associated with development of ventilator-associated pneumonia, nosocomial infection, and organ dysfunction. Because most single blood-conservation techniques reduce blood usage by a mere 1-2 units, a series of integrated conservation approaches are required. These include preoperative autologous donation, use of erythropoietic agents, blood conservation techniques such as acute normovolemic hemodilution, individualized assessment of anemia tolerance, implementation of conservative transfusion thresholds, meticulous surgical techniques, and judicious use of phlebotomy and pharmacologic agents for limiting blood loss. Erythropoietic agents such as epoetin alfa have been used successfully to increase hemoglobin and decrease transfusion requirements, and are appropriate when used in advance of elective surgical procedures. Acquisition costs of erythropoietic stimulating agents versus costs of blood justify economic evaluation by hospitals to make the most cost-effective choice under current economic constraints.. Initiating a blood management program requires planning and support from those who are concerned about blood usage reduction and outcomes improvement. Launching a vigorous and ongoing educational program to raise awareness about the risks and hazards associated with blood transfusion is an important step in helping to reshape the medical staffs' attitudes about transfusion and the most cost-effective way to achieve clinical goals.

Topics: Anemia; Blood Banks; Blood Donors; Blood Loss, Surgical; Blood Transfusion, Autologous; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Hemodilution; Hospital Costs; Humans; Insurance, Health, Reimbursement; Medicare; Recombinant Proteins

Standing orders serve an important role in various healthcare settings by empowering nurses to implement certain procedures and activities on behalf of physicians, enabling more immediate interventions, and ultimately improving patient care. Standing orders are based on established clinical practice guidelines and are well suited for supportive interventions. Several evidence-based clinical practice guidelines are available for the treatment of anemia in patients with cancer. The guidelines can serve as a basis for the development of standing orders for the management of treatment-related anemia in patients with cancer, which will enable the delivery of consistently high-quality care to patients. A major advantage to the implementation of standing orders is that patients with suboptimal hemoglobin levels can be treated by oncology nurses in a timely manner and receive high-quality care that is consistent with available clinical evidence.

Topics: Algorithms; Anemia; Clinical Protocols; Decision Trees; Drug Monitoring; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Ferritins; Hematinics; Hemoglobins; Humans; Iron; Iron-Binding Proteins; Mass Screening; Neoplasms; Nurse's Role; Nursing Assessment; Oncology Nursing; Patient Care Team; Practice Guidelines as Topic; Professional Autonomy; Quality Assurance, Health Care; Recombinant Proteins; Safety Management; Transferrin

Anemia and the need for red blood cell transfusions are common among patients admitted to intensive care units. Erythropoietin has been used to decrease the need for transfusions; however, its ability to improve clinical outcomes is unknown. We evaluated the effect of erythropoietin-receptor agonists on clinically important outcomes, including mortality, length of stay in hospital or intensive care unit, ventilator use, transfusion requirements and major adverse events.. To identify relevant studies, we searched electronic databases covering 1950 to 2007 (MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the Scopus database). We also searched conference proceedings and grey literature sources. We selected all randomized controlled trials involving critically ill patients that compared an erythropoietin-receptor agonist with a placebo or no intervention. No language restrictions were considered. Data were extracted using a standardized extraction template. We used a fixed effects model to calculate all summary measures of treatment effects.. Of 673 identified records, 9 studies that investigated erythropoietin alpha met the eligibility criteria and were included in our analysis. Erythropoietin, compared with placebo or no intervention, had no statistically significant effect on overall mortality (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.71-1.05, I2 = 0%). The treatment and control groups did not differ in the length of stay in hospital or intensive care unit, or in the duration of mechanical ventilation, in the 3 studies that reported these outcomes. Erythropoietin, compared with placebo, significantly reduced the odds of a patient receiving at least 1 transfusion (OR 0.73, 95% CI 0.64-0.84, I2 = 54.7%). The mean number of units of blood transfused per patient was decreased by 0.41 units in the erythropoietin group (95% CI 0.10-0.74, I2 = 79.2%). Most of the included studies were performed before the widespread adoption of a restrictive transfusion strategy. Only 1 study provided detailed reports of adverse events, and none of the studies systematically evaluated all patients for venous thromboembolism.. At this time, we do not recommend the routine use of erythropoietin-receptor agonists in critically ill patients. The reduction in red blood cell transfusions per patient was very small, and there is insufficient evidence to determine whether this intervention results in clinically important benefits with acceptable risks.

Topics: Anemia; Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Randomized Controlled Trials as Topic; Receptors, Erythropoietin; Recombinant Proteins

Anemia treatment in nondialysis chronic kidney disease (ND-CKD) and dialysis CKD patients (D-CKD) has been recently scrutinized in the literature and by the lay press. New evidence suggests that patients receiving epoetin and achieving higher hemoglobin have a higher risk of death and cardiovascular complications. Data from the Centers for Medicare & Medicaid Services demonstrate upward spiraling costs of injectables, especially epoetin, in the care of CKD patients. There is considerable literature favoring the use of subcutaneous administration of epoetin compared to intravenous route in hemodialysis patients. Evidence clearly shows that the subcutaneous route achieves the target hemoglobin level at a lower administered dose. Thus, the same clinical effect can be achieved at a lower cost. Despite the economic and evidentiary justifications for subcutaneous administration of epoetin, adoption of this strategy has been limited, especially in the United States. Reasons include: inflexibility by dialysis providers because of reduced profitability, claims that patients oppose the subcutaneous route because of pain at the site of injection, concerns regarding pure red cell aplasia associated with subcutaneous administration, and greater hemoglobin cycling with the subcutaneous route. In this article, the advantages and disadvantages of the subcutaneous route are reviewed.

Topics: Anemia; Biological Availability; Diffusion of Innovation; Drug Costs; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Half-Life; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Metabolic Clearance Rate; Nephrology; Patient Selection; Practice Guidelines as Topic; Practice Patterns, Physicians'; Recombinant Proteins; Renal Dialysis; Treatment Outcome; United States

Stage 3 chronic kidney disease (CKD), which is characterized by a glomerular filtration rate of 30 to 60 mL/min/1.73 m2 (reference range, 90-200 mL/min/1.73m2 for a 20-year-old, with a decrease of 4 mL/min per decade), affects approximately 8 million people in the United States. Anemia is common in patients with stage 3 CKD and, if not corrected, contributes to a poor quality of life. Erythropoiesis-stimulating agents (ESAs), introduced almost 2 decades ago, have replaced transfusions as first-line therapy for anemia. This review summarizes the current understanding of the role of ESAs in the primary care of patients with anemia of CKD and discusses pharmacological and pharmacoeconomic issues raised by recent data. Relevant studies in the English language were identified by searching the MEDLINE database (1987-2006). Two ESAs are currently available in the United States, epoetin alfa and darbepoetin alfa. More frequent dosing with epoetin alfa is recommended by the labeled administration guidelines because it has a shorter half-life than darbepoetin alfa. Clinical experience also supports extended dosing intervals for both these ESAs. Use of ESAs in the management of anemia of CKD is associated with improved quality of life, increased survival, and decreased progression of renal failure. Some evidence suggests that ESAs have a cardioprotective effect. However, correction of anemia to hemoglobin levels greater than 12 g/dL (to convert to g/L, multiply by 10) appears to increase the risk of adverse cardiac outcomes and progression of kidney disease in some patients. The prescription of ESAs in the primary care setting requires an understanding of the accepted use of these agents, the associated pharmacoeconomic challenges, and the potential risks. This review considers the need to balance effective ESA dosing intervals against the potential risks of treatment.

Topics: Anemia; Chronic Disease; Darbepoetin alfa; Disease Progression; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Ferric Compounds; Ferritins; Heart Failure; Hematinics; Humans; Kidney Diseases; Physician's Role; Primary Health Care; Quality of Life; Recombinant Proteins

The safety and efficacy of extended-dosage-interval regimens of erythropoiesis-stimulating agents (ESAs) for managing chemotherapy-induced anemia (CIA) are reviewed.. Anemia is a frequent complication of chemotherapy. The ESAs epoetin alfa and darbepoetin alfa have been shown to safely and effectively manage CIA; comparable outcomes have been demonstrated between epoetin alfa 40,000 units once weekly and darbepoetin alfa 200 microg every two weeks. These commonly prescribed regimens necessitate extra clinic visits by cancer patients receiving cyclic chemotherapy. ESA administration can now often be synchronized with a three-week chemotherapy cycle because of the recent approval of darbepoetin alfa 500 microg every three weeks for CIA. However, in the Phase III trial providing the basis for this new dosage recommendation, more than 70% of patients required a 40% reduction in the dosage, resulting in an average dose of 375 microg every three weeks. The extended-dosage-interval regimens have not been associated with an increase in cardiovascular or thrombotic adverse events. Extended-dosage-interval regimens of epoetin alfa are under investigation and may provide additional alternatives. Synchronizing ESA therapy with scheduled chemotherapy visits would help minimize disruptions for patients and caregivers and improve the use of health care resources.. Administration of darbepoetin alfa every three weeks offers the convenience of synchronization of treatment with 21-day-cycle chemotherapy in many patients with CIA. Extended-dosage-interval regimens for epoetin alfa are being investigated and show promise.

Topics: Anemia; Antineoplastic Agents; Drug Administration Schedule; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Humans; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Neoplasms; Recombinant Proteins

To review and compare the data concerning the clinical activity of epoetin alfa versus darbepoetin alfa when administered to patients with cancer who are experiencing treatment-related anemia.. English-language publications from the MEDLINE database (1990-June 2005), published articles, and meeting abstracts were reviewed.. Relevant data were extracted from published reports and abstracts on studies of humans with cancer who developed treatment-related anemia and were treated with epoetin alfa or darbepoetin alfa.. Epoetin alfa and darbepoetin alfa are similar agents with identical indications for treatment of anemia in patients with cancer. Clinical trials have demonstrated that both agents can significantly improve hemoglobin levels, reduce transfusion requirements, and improve quality of life. Epoetin alfa is approved for administration at a dose of 150 units/kg subcutaneously 3 times per week, and darbepoetin alfa is approved for administration at a dose of 2.25 units/kg once a week. Clinical studies have demonstrated that epoetin alfa may be administered at 40,000 units once a week and that darbepoetin alfa may be administered at 200 microg every 2 weeks without loss of efficacy. Cost analysis, based on the average wholesale price of each drug alone administered for 12 weeks at Food and Drug Administration-approved doses, revealed that epoetin alfa is less expensive than darbepoetin alfa. When they are administered in the extended schedules, the cost of darbepoetin alfa is slightly less than that of epoetin alfa. However, the total expense associated with the extended schedule of either agent is further reduced by a reduction in other costs associated with drug administration.. Epoetin alfa and darbepoetin alfa have identical indications for treatment of anemia in patients receiving cancer chemotherapy. Clinical trials have demonstrated similar activities with both agents. Darbepoetin alfa, with a longer half-life, can be administered less frequently, saving costs as well as reducing patient office visits.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

The introduction of recombinant human erythropoietin to the management of anemia in cancer patients has resulted in significant reductions in allogeneic blood transfusions, while at the same time contributing to improvements in quality of life. A recent meta-analysis of five randomized, placebo-controlled trials with patient-level data revealed that, while epoetin alfa was very effective in reducing transfusions compared with placebo, patients who were pretransfused were twice as likely to subsequently be transfused during epoetin alfa treatment.. To further assess the validity of this rather provocative concept, another integrated analysis was conducted with patient-level data from three Canadian trials, with a combined total of 665 patients receiving epoetin alfa treatments for their cancer- and chemotherapy-induced anemia.. Once again, pretransfusion was the most significant baseline predictor of transfusion, with patients that were pretransfused having a significantly greater likelihood of being transfused than their transfusion-naive counterparts. Furthermore, and corroborating previous findings, baseline hemoglobin (Hb) level was again found to be a significant predictor of transfusion, with patients who were treated at a baseline Hb level < 10 g/dl having a higher chance of being transfused than patients in whom epoetin alfa was initiated at baseline Hb levels of 10-11 g/dl. In addition, when the total units transfused in patients receiving epoetin alfa at different baseline Hb levels were analyzed, >85% of the units of blood transfused were received by patients with baseline Hb levels < 10 g/dl.. These data strongly suggest that early treatment with epoetin alfa could significantly optimize clinical benefit in reducing the use of transfusion in cancer patients receiving chemotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Canada; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Neoplasms; Recombinant Proteins; Risk; Risk Factors; Time Factors

Most patients with chronic kidney disease eventually become anemic. We should view the management of anemia in these patients as part of the overall management of the many clinically relevant manifestations of chronic kidney disease. Erythropoiesis-stimulating agents (ESAs) are safe and should be used, as treating anemia may forestall some of the target-organ damage of chronic kidney disease.

Topics: Anemia; Anemia, Iron-Deficiency; Chronic Disease; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Iron; Kidney Diseases; Practice Guidelines as Topic; Recombinant Proteins; Renal Dialysis

As with other groups of chronic kidney disease patients, the treatment of anaemia is of paramount importance in the general management of patients receiving regular peritoneal dialysis. The availability of agents able to stimulate erythropoiesis has transformed the management of anaemia in CKD, but questions are still raised as to the optimum means of using these drugs. Iron management is also pivotal to the satisfactory correction of anaemia, and again there is much discussion as to whether oral or intravenous iron is the preferred mode of administration in peritoneal dialysis patients. On the basis of the published evidence to date, PD patients should maintain a haemoglobin above 11 g/dL in line with the US and the European Anaemia guidelines, and intravenous iron should be used to correct any iron deficiency. Oral iron may be effective in a minority of patients. This article aims to explore some of these issues in greater detail so that patients on peritoneal dialysis can derive the greatest benefits from correction of anaemia and maintenance of an adequate haemoglobin.

Topics: Anemia; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hemoglobins; Humans; Iron; Peritoneal Dialysis; Peritonitis; Recombinant Proteins

The Standards, Options and Recommendations on the use of erythropoietin in cancer patients are recalled. The recent literature is analysed and allows some further comments to the SOR. Medico-economic aspects, new schedules of administration, extra-hematologic virtues of erythropoietin and its impact on cancer outcomes are debated.

Topics: Adult; Anemia; Brain; Child; Cognition Disorders; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Heart; Hematinics; Humans; Medical Oncology; Practice Guidelines as Topic; Recombinant Proteins

Erythropoiesis-stimulating proteins (ESPs) are indicated for the treatment of chemotherapy-induced anemia (CIA). Evidence-based guidelines and systematic reviews of the management of CIA do not yet include all currently approved ESPs or all of the clinically relevant benefits and risks of ESPs.. The aims of this work were to provide up-to-date assessments of the clinical efficacy and effectiveness (ie, transfusions and quality-of-life [QoL] benefits) and safety (ie, risk of venous thromboembolism [VTE] and all-cause or treatment-associated death) of epoetin-alfa, epoetin-beta, and darbepoetin-alfa for the treatment of CIA in cancer patients with hemoglobin<11 g/dL. We also considered the impact of differences in study design, patients, and treatments on the results.. A systematic review of the literature was performed to identify and analyze English-language studies (controlled trials and prospective uncontrolled studies with >or=300 patients) published between 1980 and July 2005. The databases searched were MEDLINE and the Cochrane Library. Relevant abstracts from the last 2 annual meetings of the American Society of Clinical Oncology, American Society of Hematology, and European Society for Medical Oncology were also included. Studies were selected, using predefined eligibility criteria. Two reviewers had to agree on all included and excluded studies, and on all data extracted from each accepted study before they were entered into a relational database. Meta-analyses were performed to quantify benefit and risk outcomes.. In total, 40 studies including 21,378 patients were eligible for analysis. Each ESP was found to have efficacy relative to standard care or placebo. The odds ratio (OR) for transfusions in studies of epoetin versus controls was 0.44 (95% CI, 0.35-0.55) and of darbepoetin versus controls was 0.41 (95% CI, 0.31-0.55). Patients receiving ESPs experienced a significant improvement in QoL; the mean difference in Functional Assessment of Cancer Therapy-Fatigue score for ESPs versus controls was 0.23 (95% CI, 0.10-0.36; P=0.001). The frequency of VTE and death was not significantly different between ESPs and control (VTE OR, 1.41 [95% CI, 0.81-2.47]; all-cause mortality OR, 1.00 [95% CI, 0.69-1.44]).. This analysis of key clinical benefits and risks of epoetin and darbepoetin in the treatment of CIA found no clinically relevant differences between these drugs.

Topics: Adult; Anemia; Antineoplastic Agents; Blood Transfusion; Child; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Quality of Life; Recombinant Proteins; Thromboembolism; Venous Thrombosis

Anemia is common in patients with hematologic malignancies, and it has negative effects on their quality of life. The current clinical practice guidelines recommend erythropoietic therapy in patients with cancer- or chemotherapy-related anemia, but anemia is often undertreated in patients with hematologic malignancies. Several randomized controlled trials have shown that treatment with erythropoiesis-stimulating proteins such as epoetin alfa (Procrit), epoetin beta, and darbepoetin alfa (Aranesp) increases hemoglobin levels, reduces the need for red blood cell transfusions, and improves quality of life in patients with hematologic malignancies and anemia receiving chemotherapy. Furthermore, preliminary data from a recent open-label study suggest that early treatment of mild anemia in patients with hematologic malignancies treated with chemotherapy produces marked improvements in quality of life and productivity. Increasing patients' hemoglobin levels may also improve their cognitive function. These findings support the use of erythropoietic therapy to manage anemia in patients with hematologic malignancies who are treated with chemotherapy.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematologic Neoplasms; Humans; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins

Anemia is common in patients treated with chemotherapy for both solid and hematologic malignancies, contributing to fatigue and diminished quality of life and exposing them to the inherent risks of red blood cell transfusions. Erythropoiesis-stimulating proteins have been shown to increase hemoglobin levels, reduce the need for transfusions, and improve quality of life. The current practice guidelines recommend treating moderate to severe chemotherapy-induced anemia with erythropoiesis-stimulating proteins, but the risk of transfusions may be less with earlier intervention at higher hemoglobin levels. A review of the literature suggests that treating mild chemotherapy-induced anemia with erythropoiesis-stimulating proteins reduces the risks of transfusions and the development of more-severe anemia. Weighing the clinical evidence together with other clinical and economic considerations should provide greater insight into the benefits of treating mild anemia in patients treated with chemotherapy.

Topics: Anemia; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Time Factors

As with many other therapeutic areas in modern-day medicine, scientific advances in drug development (using such techniques as recombinant DNA technology, site-directed mutagenesis, pegylation of molecules, peptide library screening, and gene transfer) have resulted in the development of potential new agents and strategies for stimulating erythropoiesis. These advances are of possible benefit in treating anaemia due to various causes, including chronic renal failure. Several new treatments will soon become clinically available, while others are at present at an early stage of development but are nevertheless of scientific interest. We review these new therapeutic strategies, and discuss at what stage some of the newer products are in relation to their clinical development programme.

Topics: Anemia; Animals; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Recombinant Proteins

Topics: Anemia; Darbepoetin alfa; Diabetes Mellitus; Epoetin Alfa; Erythropoietin; Heart Failure; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Treatment Outcome

Anemia is a frequent complication of chronic kidney disease (CKD). Inadequate production of erythropoietin by the failing kidneys leads to decreased stimulation of the bone marrow to produce red blood cells (RBCs). Anemia of CKD develops early and worsens with progressive renal insufficiency. Although over 40% of patients with CKD are anemic, anemia in this population is under-recognized and undertreated. Of considerable importance, anemia is a risk factor for cardiovascular disease and is associated with higher rates of hospitalization and mortality. Despite the availability of erythropoiesis-stimulating proteins (ESPs) to stimulate RBC production in CKD patients, approximately three fourths of patients initiating dialysis have a hemoglobin <11 g/dL. The recognition of anemia of CKD begins with an estimation of glomerular filtration rate (GFR), which can be far lower than a normal serum creatinine might suggest, especially in the elderly and in those with poor nutrition and muscle mass. If GFR is <60 mL/min/1.73 m(2), hemoglobin should be checked. The anemia is diagnosed when the hemoglobin is <12 g/dL in a man or a postmenopausal woman, or <11 g/dL in a premenopausal woman. The cause of anemia should be investigated in these individuals; this can range from erythropoietin deficiency due to CKD, to deficiency of vitamin B(12) and/or folate, iron deficiency, blood loss, inflammation, malignancy, and aluminum intoxication. After other causes of anemia have been excluded, CKD is the most likely etiology, and it should be treated with an ESP. Currently, epoetin alfa and darbepoetin alfa are the only 2 ESPs approved for use in the United States. Extended dosing of ESP has potential advantages for the patient and may also improve resource utilization. Consequently, both agents have been tested for dosing at extended intervals. Adequate iron stores--defined as transferrin saturation >20% and ferritin >100 mg--as well as ESP administration are needed to produce an appropriate increase in hemoglobin. Poor response to treatment with ESP can be due to many factors, including presence of iron deficiency, inflammation, continued blood loss, and hemoglobinopathy.

Topics: Age Distribution; Aged; Anemia; Causality; Creatine; Darbepoetin alfa; Drug Administration Schedule; Drug Monitoring; Epoetin Alfa; Erythropoietin; Female; Ferritins; Glomerular Filtration Rate; Hematinics; Hemoglobins; Humans; Iron Compounds; Kidney Failure, Chronic; Male; Nutritional Status; Practice Guidelines as Topic; Recombinant Proteins; Risk Factors; Sex Characteristics; Transferrin; Treatment Failure

The purpose of this study was to review and analyze current research to evaluate the dose ratio of epoetin alfa and darbepoetin alfa for the treatment of anemia in chronic kidney disease (CKD) and to identify determinants of the variation in epoetin alfa:darbepoetin alfa dose ratios across studies.. A systematic review of the literature for comparative switch and non-switch studies of epoetin alfa and darbepoetin alfa treatments in CKD for the period 2000-2005 was performed. Two reviewers independently assessed the quality of the information. Data on the study design and outcomes were collected for each selected study. The dose ratio from epoetin alfa to darbepoetin alfa was calculated for each study, and the results were reported stratified by study characteristics. To control for differences in study design and characteristics that could explain the variability in the relative dosages of the two agents across studies, multivariate regression analysis was conducted. Based on these results, a dose conversion ratio for Canada was estimated.. A total of 21 studies involving 16 378 patients exposed to epoetin alfa or darbepoetin alfa in CKD were identified. Univariate analysis of the dose ratios indicated a mean dose ratio of 217:1 (IU of epoetin alfa:mug of darbepoetin alfa). Results from the multivariate analysis demonstrated that the study design (i.e., switch study versus straight comparison studies) and geographical coverage (i.e., United States) affected the results. Based on the multivariate analysis, the dose conversion ratio between epoetin alfa and darbepoetin alfa for Canada was 169:1.. Despite limitations associated with switching studies and the limited total number of studies available, this systematic review based on aggregated results provides further evidence to the clinical community that the dose conversion ratio for epoetin alfa:darbepoetin alfa in CKD patients in Canada is approximately 169:1. At that ratio, treatment with epoetin alfa is 11-18% cheaper than treatment with darbepoetin alfa in Canada.

Topics: Anemia; Chronic Disease; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Humans; Kidney Diseases; Multivariate Analysis; Recombinant Proteins

Anaemia is considered a common problem in many cancers secondary to the disease itself or related to chemo- and/or radiotherapy. Several clinical trials have advocated the prognostic value of anaemia and hypoxia in the outcome of many cancers. Erythropoietin is recognised as an effective treatment for anaemia, which also improves the quality of life in patients with malignant disease. External radiotherapy plays an important role in the treatment of loco-regional cancer but its efficacy can be compromised by many factors. Tumor hypoxia is considered by many authors as an important factor contributing to radioresistance. We report in this article the radiobiological rationale in favour of combining radiotherapy and erythropoietin, and review relevant clinical papers published in this field.

Topics: Anemia; Clinical Trials as Topic; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Treatment Outcome

Anaemia, often associated with chemotherapy, is a common and debilitating disorder in cancer patients. Recombinant human erythropoietin (epoetin alfa) was introduced in the 1990s for the treatment of chemotherapy-related anaemia. Data from randomised, double-blind, placebo-controlled studies and large, non-randomised, community-based studies have demonstrated that either of the FDA-approved dosing schedules of epoetin alfa 150 - 300 U/kg three times weekly or 40,000-60,000 U/week s.c., significantly increases haemoglobin levels, reduces transfusion requirements, and improves quality of life in anaemic cancer patients undergoing chemotherapy or chemoradiation therapy. Guidelines for the effective and safe use of epoetin alfa have been published by major oncology/haematology organisations and are reviewed in this article. Areas of recent and ongoing investigation with epoetin alfa are also covered in this review.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins

Anemia occurring in patients with renal failure on dialysis has been shown to both increase transfusion requirements and decrease functional status and quality of life. As a result, treatment of these patients with an erythropoietic agent such as epoetin alfa or darbepoetin alfa has become established as an essential part of optimal patient care. Anemia resulting from cancer or chemotherapy is a common problem in oncology, and has been shown similarly to increase transfusion risk and decrease patient reported outcomes. For reasons that are not clear, but may include either frequently encountered slow response or nonresponse and higher doses and hence higher costs, treatment of anemia in oncology has not become a standard treatment for all patients. Erythropoietic agents (epoetin alfa and darbepoetin alfa) have been used to improve anemia-related fatigue and quality of life in cancer patients. Epoetin is administered 1 to 3 times per week whereas darbepoetin, with up to a 3-fold greater half-life, is given once every 1 or 2 weeks. Recent data demonstrate that darbepoetin can be administered as infrequently as every 3 weeks with comparable erythropoietic efficacy. Several studies have been carried out to determine the optimum schedule of dosing to obtain maximum patient benefit. Following treatment with darbepoetin, antibodies to darbepoetin were not detected, no unusual adverse event was seen with darbepoetin, and the mean increase in hemoglobin remained unchanged when the dosing interval was increased from 1 to 2 weeks. The safety and efficacy of darbepoetin was also determined in patients with solid tumors receiving chemotherapy; the lowest clinically effective dose was determined to be 3.0 and 5.0 microg/kg every 2 weeks with a 66 and 84% response, respectively. No additional benefit was seen with higher doses. A multicenter study evaluated the safety and efficacy of darbepoetin administered either weekly, every 3 weeks, or every 4 weeks in anemic patients with cancer who were not receiving chemotherapy or radiotherapy. The results indicated that with weekly dosing, 70% of patients showed an increase in hemoglobin. The dose of 4.5 microg/kg/week resulted in 100% hematopoietic response. In a randomized, active control, pilot trial, front-loading darbepoetin followed by lower doses or less frequent doses also appears to be efficacious and may decrease the time to response. At the present time, darbepoetin improves anemia, reduces requirements for transfus

Topics: Anemia; Clinical Trials, Phase III as Topic; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Treatment Outcome

Improving anemia in patients with chronic renal failure (CRF) and congestive heart failure (CHF) also improves left ventricular hypertrophy (LVH). No previous meta-analyses have been conducted to further examine this association, including the association between LVH and mortality in these patients.. Literature searches on MEDLINE, EMBASE, and OVID were performed using Cochrane Library protocols. Two hundred sixteen abstracts were reviewed preliminarily for inclusion in the meta-analysis of epoetin alfa, anemia and 5 pre-selected parameters of LVH. One hundred seventy-nine abstracts were reviewed for LVH and mortality. The predominant hematologic and left ventricular function changes observed during epoetin alfa treatment in patients with CHF and CRF are (1) increases in hemoglobin (Hb) and hematocrit (Hct); (2) decreases in left ventricular mass (LVM) and LVM index; (3) increase in ejection fraction (EF); and (4) decreases in left ventricular end-diastolic and end-systolic volume. Three independent factors-target Hb, duration of disease, and duration of follow-up-each had a statistically significant association with Hb, Hct, and EF, respectively. A separate meta-analysis using 3 risk models showed LVH is strongly and positively associated with both cardiovascular and all-cause mortality, with two- to three-fold increases in risk.. LVH is common in patients with CRF and CHF. Current findings indicate epoetin alfa therapy results in anemia amelioration, as evidenced by higher Hb and Hct levels, and reduction of key LVH parameters. LVM regression is associated with lower incidence of cardiovascular-related morbidity and mortality, therefore epoetin alfa therapy may provide a survival benefit.

Topics: Adult; Anemia; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Regression Analysis; Ventricular Function, Left

In gynaecology, anaemia treatment is indicated in extremely different situations. In cancer patients, treatment with epoetin can relieve fatigue and improve quality of life. In these patients, epoetin treatment can also have a positive influence on survival through increasing the efficacy of radiotherapy and chemotherapy. Recent data are presented. In gynaecological surgery, the use of epoetin--based on results in oncology and orthopaedic surgery--makes a constructive contribution to the improvement of quality of life and during patient recovery through rapid normalisation of perioperative anaemia, thus reducing the risk of a transfusion with donated blood. Encouraging data from recent publications concerning the prevention of PRCA under epoetin treatment are presented.

Topics: Adult; Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Humans; Pregnancy; Pregnancy Complications; Quality of Life; Recombinant Proteins; Risk Factors

Topics: Anemia; Epoetin Alfa; Erythropoietin; Forecasting; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; United States

European and US guidelines for renal anaemia management recommend subcutaneous (s.c.) epoetin as the preferred route of administration in pre-dialysis, peritoneal dialysis and haemodialysis patients. However, the restriction of Eprex/Erypro to intravenous (i.v.) administration in Europe has increased the interest of health care professionals regarding the optimal route of administration for all epoetin formulations. There are five major considerations for the 'optimal' route of epoetin administration: efficacy; dosing frequency; convenience; safety and tolerability; and cost. Although epoetin bioavailability is lower after s.c. administration, its efficacy is higher, owing to its prolonged elimination half-life compared with i.v. epoetin. Several studies and clinical surveys comparing s.c. and i.v. administration have demonstrated that equivalent target haemoglobin levels can be maintained at much lower doses of epoetin when administered s.c. Furthermore, s.c. epoetin dosing frequency can be reduced in some patients to once every 2 weeks, without compromising efficacy. Devices such as the Reco-Pen have been specifically designed to facilitate self-administration of s.c. epoetin-beta. An upsurge in the incidence of pure red cell aplasia (PRCA) was linked to the epoetin-alpha product Eprex/Erypo in Europe, and an increase in PRCA cases of the same magnitude was not seen in patients taking other epoetin products s.c. Therefore, PRCA should not be used as an argument against s.c. administration. The reduced dose with s.c. administration of epoetin-beta provides significant cost benefits, without compromising either safety or efficacy, and may also increase patient satisfaction and compliance with treatment.

Topics: Anemia; Drug Administration Schedule; Drug Costs; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure; Treatment Outcome

The combination of diabetes and chronic kidney disease is associated with increased mortality and reduced quality of life. Recent studies have shown that, in general, late referral of patients to the renal unit increases mortality, and that patients with diabetes who are referred late have a particularly poor prognosis. Several co-morbid conditions have been shown to contribute to poor patient outcomes, including both cardiovascular disease and anaemia. In patients with diabetic nephropathy, anaemia is more severe and is seen earlier than in patients with non-diabetic renal disease. Although the treatment of anaemia with recombinant human erythropoietin (rhEPO; epoetin) is well established, the only data currently available concerning the effects of early intervention in patients with diabetic nephropathy are from small-scale studies. Therefore, two large-scale studies have been designed to provide information on the efficacy of epoetin treatment and on how current management strategies might be improved. The Anaemia CORrection in Diabetes (ACORD) study will provide information on the potential cardiac benefits of early anaemia management in patients with early, type 2 diabetic nephropathy. The Individualised Risk-profiling In DIabEtes Mellitus (IRIDIEM) study will provide evidence-based guidance in risk factor management, by assessing the efficacy of individualized interventions.

Topics: Anemia; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Referral and Consultation; Survival Rate

Treatment with epoetin alfa has repeatedly been shown to improve the quality of life (QoL) of cancer patients with anaemia. We used meta-analytical techniques to synthesise data from all available (published and unpublished) studies of epoetin alfa in cancer patients receiving chemotherapy that used validated QoL instruments. Results from 23 studies were synthesised. These employed the CLAS, FACT, SF-36 and ECOG (WHO) QoL scales. The meta-analysis indicated that treatment with epoetin alfa was associated with a clear and statistically significant improvement in QoL as measured by all subscales of CLAS, all subscales of FACT, and 5 subscales of SF-36. In contrast, control groups experienced no significant change, or, in some cases, a deterioration in QoL. Improvement was related to treatment duration. The generic ECOG (WHO) performance scale indicated that, even though epoetin alfa treatment is associated with clear benefits in terms of QoL, this population of patients receiving chemotherapy for cancer experience a gradual decrease in functional status over time.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Neoplasms; Quality of Life; Recombinant Proteins

The management of cancer-related anemia with erythropoietic agents presents many unresolved issues. We reviewed the literature relating to epoetin alfa (Eprex)/Epypo); Ortho Biotech/Janssen-Cilag, High Wycombe, United Kingdom, http://www.orthobiotech.co.uk; Procrit); Ortho Biotech Products, L.P., Bridgewater, NJ, http://www.orthobiotech.com), epoetin beta (NeoRecormon); Hoffman-La Roche, Basel, Switzerland, http://www.roche.com), and darbepoetin alfa (Aranesp); Amgen Inc., Thousand Oaks, CA, http://www.amgen.com) highlighting the results of published clinical trials, safety, and cost-effectiveness. Studies were identified through MEDLINE and the bibliographies of relevant articles. Epoetin alfa, epoetin beta, and darbepoetin alfa have differing pharmacokinetic and pharmacodynamic profiles. They are all effective at reducing transfusion requirements and improving health-related quality-of-life parameters, irrespective of tumor response. A direct comparison between epoetin alfa and darbe poetin alfa is based on limited evidence, which does not allow definitive conclusions about relative efficacy and cost-effectiveness. No predictive factors for response to erythropoietic agents have been validated in prospective trials. The most consistent adverse events are thrombotic and may occur irrespective of an increase in hemoglobin. Recent research indicates that the erythropoietin receptor is expressed in several cancer cell lines, raising the concern of possible stimulation of tumor cell growth by these drugs. Studies on the cost-effectiveness of erythropoietins, particularly compared with transfusion therapy, have been challenging to conduct and analyze and have generated ambiguous results. The use of erythropoietins needs to be optimized in terms of cost-effectiveness, and issues surrounding safety need to be clarified. A stronger methodology for clinical studies and the design of new, randomized, clinical trials is a major priority.

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Consensus guidelines are in place for treating chronic hepatitis C virus infection. This article highlights some of the hematologic complications of hepatitis C therapy. Management options are presented.

Topics: Anemia; Antiviral Agents; Bone Marrow; Epoetin Alfa; Erythropoietin; Hematologic Diseases; Hepatitis C, Chronic; Humans; Interferon Type I; Neutropenia; Recombinant Proteins; Ribavirin; Thrombocytopenia

Anaemia is a common complication of cancer and its treatment. It is also associated with substantial impairment of patient quality of life (QOL). Erythropoietic agents are primary treatment options for cancer-related anaemia (CRA). This review summarises evidence supporting clinical use of the approved erythropoietic agents (epoetin alfa, epoetin beta, darbepoetin alfa). A MEDLINE((R)) search from January 2000 to September 2004 using the search terms "epoetin alfa," "epoetin beta," "darbepoetin alfa," "erythropoietin," and "anaemia" was conducted to identify studies evaluating erythropoietic agents in the treatment of CRA. Recent presentations at professional meetings were also included. Erythropoietic agents increase haemoglobin levels, decrease transfusion requirements, and improve QOL in patients with CRA. However, variations in study design, patient populations, dose titration schedules, and outcome measures among available studies make data comparisons between clinical trials difficult. Head-to-head trials are comparing erythropoietic agents in a randomised setting; other trials are evaluating optimal dosage schedules. Clinically relevant differences among approved erythropoietic agents have not been determined in direct comparative trials; however, epoetin alfa appears to be at least as effective as darbepoetin alfa in treatment of CRA.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Evaluation; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Anemia occurs in virtually all critically ill patients receiving long-term mechanical ventilation and has been associated with increased mortality and poor outcomes. Allogeneic RBC transfusions are routinely administered to critically ill anemic patients, especially during lengthy stays in ICUs or in long-term acute care facilities. Although RBC transfusions are a physiologically rational approach to raising hemoglobin levels, they may increase the risk of complications and have been associated with higher mortality in critically ill patients. Treatment with epoetin alfa, an erythropoiesis-stimulating agent, as a means of reducing transfusion requirements has been studied in the critically ill and in patients receiving long-term mechanical ventilation. Promising results have been reported, including a potential survival benefit, although larger and more definitive studies are needed in order to establish whether raising hemoglobin levels affects clinical outcomes in patients receiving mechanical ventilation.

Topics: Anemia; Blood Banks; Comorbidity; Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Hemoglobins; Humans; Recombinant Proteins; Respiration, Artificial; Respiratory Insufficiency; Time Factors; Ventilator Weaning

Perioperative anemia is common and is associated with increased need for blood transfusion in the perioperative period. Perioperative anemia has also been linked to increased morbidity and mortality in surgical patients. Anemia may impede a patient's ability to recover fully and participate in postoperative rehabilitation. Pre-operative treatment of anemia is associated with a reduction in the need for blood transfusion in the perioperative period. Additional advances in surgical technology that reduce blood loss intraoperatively are associated with a reduction in postoperative anemia and should be used whenever possible. All strategies to prevent anemia in the perioperative period should be considered in an effort to minimize exposure of surgical patients to blood transfusion.

Topics: Anemia; Blood Transfusion; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Perioperative Care; Postoperative Care; Postoperative Complications; Preoperative Care; Primary Prevention; Recombinant Proteins; Risk Assessment; Severity of Illness Index; Surgical Procedures, Operative

Anemia in cancer patients undergoing treatment is common and can cause debilitating symptoms such as fatigue and reduced exercise tolerance. The introduction of recombinant human erythropoietin represents a potential improvement in the treatment of this condition. Clinical studies in patients with solid tumors and nonmyeloid hematologic malignancies have convincingly shown an improvement in mean hemoglobin concentration, a reduction in transfusion requirement along with an improvement in quality of life scores, although an effect on survival is less clear. In myeloid disorders such as myelodysplasia, response to single-agent recombinant human erythropoietin is disappointing but significant synergism with granulocyte colony stimulating factor has been demonstrated and different dosing regimens may also improve response. Unfortunately, a significant proportion of patients remain refractory to treatment. Efforts have been made to identify treatable causes of erythropoietin refractoriness, such as functional iron deficiency, and concomitant intravenous iron supplementation does appear to improve response rates. The search for pretreatment factors that predict response has been largely disappointing, although a promising model for myelodysplasia has been developed that awaits large-scale evaluation. Recombinant human erythropoietin is well tolerated, although there were concerns in the late 1990s due to a rising incidence of pure red cell aplasia in chronic renal failure patients treated with subcutaneous Eprex (Ortho Biologics) in Europe. Since potentially contributory manufacturing processes have been identified and corrected, the incidence of this complication has been falling.

Topics: Anemia; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Hemoglobins; Humans; Neoplasms; Prognosis; Quality of Life; Recombinant Proteins

Analysis of the biologic effects of erythropoietin and pathophysiology of chronic kidney diseases (CKD) suggests that treatment with erythropoiesis-stimulating agents (ESA) could slow the progression of CKD. By decreasing hypoxia and oxidative stress, it could prevent the development of interstitial fibrosis and the destruction of tubular cells. It could have direct protective effects on tubular cells through its antiapoptotic properties. It could help maintain the integrity of the interstitial capillary network through its effects on endothelial cells. Thus, suggesting that correcting anemia with ESA could slow the progression of CKD is biologically plausible. In patients with CKD, three small prospective studies and a retrospective study have suggested that treatment with ESA may have protective effects. Post-hoc analysis of the Reduction in Endpoints in Noninsulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan study has also shown that anemia was an independent risk factor for progression of nephropathy in patients with type 2 diabetes. In addition, a large clinical trial, which had to be stopped prematurely because of labeling change for subcutaneous administration of epoetin alfa, suggests that complete normalization of hemoglobin levels is safe in CKD patients not on dialysis and without severe cardiovascular disease. Thus, it seems reasonable to advocate starting a large randomized, prospective study to determine if normalization of hemoglobin concentration can effectively slow the progression of CKD.

Topics: Anemia; Apoptosis; Clinical Trials as Topic; Diabetic Nephropathies; Disease Progression; Epoetin Alfa; Erythrocyte Count; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Nephrons; Prospective Studies; Protein Binding; Receptors, Erythropoietin; Recombinant Proteins; Retrospective Studies; Risk Factors

The combination of heart failure and chronic kidney disease (CKD) has received comparatively little attention in terms of clinical research versus investigations of each state individually. It has been known for over a decade that anemia, a cardinal feature of CKD, is associated with higher cardiovascular event rates in late-stage and end-stage renal disease. Although the biological mechanisms linking anemia, renal failure, and heart failure are incompletely understood, more prevalent anemia is consistent in patients with more severe heart failure and is associated with higher mortality rates. Impaired erythropoietin production and resistance to erythropoietin are major contributors to anemia in patients with heart failure. By targeting hemoglobin levels in anemic patients with CKD, through the use of recombinant erythropoietin (epoetin) therapy, it has been hoped that anemia, CKD, and heart failure outcomes can be improved. Darbepoetin alfa was engineered to contain more N-linked carbohydrate chains than erythropoietin, and has an approximately 3 times longer serum half-life. Several clinical trials have addressed the hypothesis that darbepoetin alfa can effectively treat renal anemia at dose frequencies of once per week, or less often, with positive outcomes.

Topics: Anemia; Cardiomyopathies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins

Since its initial indication as hormone-replacement therapy in the anemia of chronic kidney disease, epoetin alfa has become a mainstay of therapy for chemotherapy-related anemia. Clinical studies have shown that epoetin alfa administered once weekly or three times weekly improves hemoglobin levels, decreases transfusion requirements, and improves quality of life independent of tumor response to chemotherapy. Ongoing research is now evaluating ways to improve the response rate to epoetin alfa, the potential benefits of alternative dosing regimens and early treatment intervention, and nonanemia-related indications (e.g., cognitive impairment, asthenia). In addition, scientists are exploring the role of epoetin alfa in preventing apoptosis and ischemic brain injury, as well as its activity in other nonerythroid tissues. Thus, the role of epoetin alfa is likely to expand in the cancer setting in the coming years.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Survival Analysis

Recombinant human erythropoietin (epoetin alfa) has been used in clinical settings for more than a decade. Its indications have expanded considerably from its original use as hormone therapy in the treatment of anemia in adults with chronic kidney disease. Since the introduction of epoetin alfa, a greater understanding of anemia pathophysiology and the interactions of erythropoietin, iron, and erythropoiesis has been elucidated. Anemia is now independently associated with increased mortality and disease progression. Potential survival benefits associated with correction of anemia in various patient populations are leading to consideration of earlier, more aggressive treatment of mild to moderate anemia with epoetin alfa. Moreover, this agent's therapeutic use may extend beyond currently accepted roles. Epoetin alfa is undergoing evaluation with promising results in a variety of new clinical settings, including anemia associated with congestive heart failure, ribavirin-interferon alfa treatment of hepatitis C virus infection, and critical illness. Preclinical studies also have established erythropoietin and its recombinant equivalent to be a pleiotropic cytokine with antiapoptotic activity and neuroprotective actions in the central nervous system. The therapeutic potential of epoetin alfa appears yet to be fully realized.

Topics: Anemia; Clinical Trials as Topic; Cytokines; Epoetin Alfa; Erythropoiesis; Erythropoietin; Heart Failure; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Quality of Life; Recombinant Proteins; United States

Numerous randomized, controlled trials have demonstrated that recombinant human erythropoietin (rHuEPO, epoetin alfa) significantly raises hemoglobin levels, reduces transfusion requirements, and improves quality of life in anemic patients with chronic renal failure. However, this accumulation of data has yet to be systematically examined. The objectives of this meta-analysis were to quantify the effects of epoetin alfa on clinical efficacy, quality of life, hospitalizations, and transfusions by collecting and analyzing the published body of evidence.. Sixteen published studies fulfilled all inclusion criteria and were subjected to data extraction. Data specifically related to hemoglobin and/or hematocrit levels, quality-of-life measurements, number and length of hospitalizations, and number of blood transfusions were then pooled across studies using a random effects meta-analysis. Simple combined estimates of the preselected variables were calculated, and adjusted estimates were made using meta-regression.. Baseline hemoglobin levels (<8 g/dL) increased substantially (40% to 50%) after epoetin alfa administration to a nonanemic state (Hb >11 g/dL) for the pooled study group. Substantial improvements (10% to 70%) were observed for all measures of quality of life. In addition, patients who received epoetin alfa had substantial reductions in hospitalization rate, hospital length of stay, transfusion rate, and number of units transfused.. This meta-analysis strongly suggests that epoetin alfa therapy for patients with chronic renal failure provides important clinical and quality-of-life benefits while substantially reducing hospitalizations and transfusions.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins

To discuss the controversies regarding the use of epoetin alfa (EPO) for reducing red blood cell (RBC) transfusions in critically ill patients with anemia.. A MEDLINE search (1966-July 2003) was conducted using the search terms anemia; critical illness; erythropoietin; epoetin alfa; and erythropoietin, recombinant. References of selected articles were reviewed for studies that may have been missed by the computerized search.. Studies pertaining to the use of EPO for anemia of critical illness with an emphasis on data obtained from controlled trials.. Anemia is a common complication in patients admitted to the intensive care unit (ICU). Two prospective, randomized studies have demonstrated decreased transfusion requirements associated with EPO administration in medical/surgical patients who were in the ICU for at least 3 days and had hematocrit concentrations <38%. No differences were found in length of stay or mortality. A multicenter trial found that a restrictive strategy of RBC transfusion (hemoglobin goal 7-9 g/dL) was associated with in-hospital mortality lower than that with a more liberal approach, which calls into question the 38% hematocrit goal in the EPO trials. Furthermore, preliminary results from an economic analysis of EPO use in the ICU setting have demonstrated that EPO is not cost-effective.. Given the controversies surrounding EPO administration in critically ill patients, institutions are encouraged to develop EPO guidelines to help ensure the most appropriate use of this expensive product. Additional studies regarding patients most likely to benefit from EPO therapy, the most effective dosing regimen, and use of adjunctive therapies are needed.

Topics: Anemia; Blood Transfusion; Critical Illness; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Intravenous; Injections, Subcutaneous; Randomized Controlled Trials as Topic; Recombinant Proteins

The pharmacoeconomics of erythropoietic therapy for the treatment of anemia is receiving renewed attention due to the current availability of two agents. Epoetin alfa has been the standard of therapy for patients with renal disease and cancer-related anemia for more than a decade. Darbepoetin alfa, an alternative agent, is now approved for anemia resulting from renal disease and cancer chemotherapy.. Although direct comparative trials have not been performed with these agents, information published in the last several years regarding their clinical efficacy, safety, and dosing is sufficient, in most cases, to compare costs. With the disclaimer that any efficacy comparison of competing products using published reports has certain limitations, a cost-minimization approach from a provider's perspective was conducted.. To provide background for the economic evaluation, pharmacokinetic and pharmacodynamic data for these two agents are discussed. Recent clinical trials in the nephrology and oncology therapeutic areas are summarized, highlighting study designs, dosing regimens, patient entry criteria, study endpoints, and published results. Cost data, based on average wholesale prices (AWP) in 2003, are compared and calculated from available clinical data with an emphasis on efficacy.. These evaluations largely conclude that epoetin alfa is the better pharmacoeconomic value of the two currently available erythropoietic agents.

Topics: Anemia; Antineoplastic Agents; Cost-Benefit Analysis; Darbepoetin alfa; Dose-Response Relationship, Drug; Economics, Pharmaceutical; Epoetin Alfa; Erythrocytes; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins; Treatment Outcome

Anaemia is common in people with cancer, and may reduce their quality of life and life expectancy. Blood transfusion can increase haemoglobin levels but is usually reserved for those with moderate anaemia (haemoglobin level below 10 g/dL). A potential alternative is treatment with one of the human recombinant forms of erythropoietin, epoetin alfa (Eprex--Janssen-Cilag) or epoetin beta (NeoRecormon--Roche), or their hyperglycosylated derivative [symbol: see text] darbepoetin alfa (Aranesp--Amgen). These products have improved the management of patients with chronic renal failure who are anaemic. Here we assess the place of the epoetins and darbepoetin alfa in managing anaemia in patients with cancer.

Topics: Anemia; Darbepoetin alfa; Drug Costs; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Survival Analysis; Treatment Outcome

In patients with human immunodeficiency virus (HIV), anemia is a commonly encountered hematologic abnormality that has a significant impact on clinical outcomes and quality of life (QOL). This review describes the prevalence of anemia in several populations of patients with HIV and the effects of anemia on survival, morbidity, disease progression, transfusion requirements, and QOL. The prevalence of anemia in HIV disease varies considerably, ranging from 1.3% to 95%: it depends on several factors, including the stage of HIV disease, sex, age, pregnancy status, and injection-drug use as well as the definition of anemia used. In general, as HIV disease progresses, the prevalence and severity of anemia increase. Anemia is also more prevalent in HIV-positive women, children, and injection-drug users than in HIV-negative women, children, and injection-drug users. Anemia has been shown to be a statistically significant predictor of progression to the acquired immunodeficiency syndrome and is independently associated with an increased risk of death in patients with HIV. Treatment of anemia with epoetin-alpha has resulted in significantly fewer patients requiring transfusion as well as decreases in the mean number of units of blood transfused. Resolution of HIV-related anemia has been shown to improve QOL, physical functioning, energy, and fatigue in individuals with HIV. More recently, the use of highly active antiretroviral therapy has also been associated with a significant increase in hemoglobin concentrations and a decrease in the prevalence of anemia.

Topics: Activities of Daily Living; Adult; Anemia; Anti-HIV Agents; Blood Transfusion; CD4 Lymphocyte Count; Child; Comorbidity; Disease Progression; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; HIV Infections; Humans; Infant; Male; Outcome Assessment, Health Care; Pregnancy; Prevalence; Quality of Life; Recombinant Proteins; Severity of Illness Index; Substance Abuse, Intravenous; Survival Analysis

Anemia is extremely common in patients with cancer. Low hemoglobin levels are associated with diminished quality of life and possibly decreased overall survival. Successful treatment of anemia has undeniable benefits for patients, often yielding dramatic symptomatic improvement that can be very satisfying for clinicians to observe. This review focuses on evolving issues in the management of anemia in patients suffering from cancer. Topics addressed include new evidence-based guidelines concerning the use of epoetin alfa, the evolving role of darbepoetin alfa in cancer-associated anemia, the potential for concomitant iron supplementation to maximize response to erythropoietic agents, the unresolved question of whether erythropoietin use affects survival in cancer patients, new concerns about the risk of thromboembolism in cancer patients with higher hemoglobin levels who are receiving epoetin, and possible immunosuppressive effects of blood product transfusions that may have relevance to neoplasia progression.

Topics: Anemia; Chemotherapy, Adjuvant; Darbepoetin alfa; Drug Therapy, Combination; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Evidence-Based Medicine; Hematinics; Humans; Iron; Neoplasms; Practice Guidelines as Topic; Quality of Life; Radiotherapy, Adjuvant; Recombinant Proteins; Thromboembolism; Treatment Outcome

Anemia is a common problem in critically ill patients. As a result, blood transfusions are often used in the intensive care unit (ICU) setting. However, mounting evidence shows that blood transfusions may contribute to negative outcomes, such as transfusion-related infections, organ dysfunction, and immunosuppression. Supplementation with epoetin alfa is currently used in some medical centers to manage anemia in critically ill patients.. This review discusses the risks with blood transfusions and the clinical evidence supporting the use of epoetin alfa in managing edema during critical illness.. A search was conducted in MEDLINE and Current Contents (1966-2003) using the terms epoetin alfa, recombinant human erythropoietin, and anemia. Articles addressing anemia and the use of epoetin alfa in critically ill patients were selected and assessed. From this selection, the cited references addressing the etiology of anemia in the ICU and the risks associated with blood transfusions were manually extracted and reviewed.. Several reports have shown that critically ill patients display evidence of anemia due to a blunted erythropoietin response. One large, randomized, placebo-controlled study assessed the effect of SC epoetin alfa on blood transfusions in the ICU. In this study, 40, 000 IU administered weekly for up to 4 weeks resulted in an overall transfusion reduction (9.9% absolute risk reduction; P<0.001 ). Other, smaller studies using different dosing regimens in critically ill patients have also demonstrated that epoetin alfa can decrease the need for transfusion.. The use of epoetin alfa in critically ill patients can decrease the number of blood transfusions required during hospitalization, and potentially result in transfusion avoidance. Because of the scarce amount of evidence and the diversity of dosing regimens used used, no strict recommendations can be drawn from this review.

Topics: Anemia; Critical Illness; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins; Transfusion Reaction

To determine the occurrence of cancer-related fatigue, the methods used to assess it, and the efficacy of the available treatments, we performed literature searches that identified English-language publications on these topics. Twenty-seven studies were identified in which the quantitative estimation of the occurrence of cancer-related fatigue was an end point. Fifty-six were judged to be relevant to the assessment of fatigue, and 10 randomized controlled clinical trials of treatments of cancer-related fatigue were retrieved. The occurrence of cancer-related fatigue was found to range from 4% to 91%, depending on the population studied and the methods of assessment. Few population-based studies and no longitudinal studies of cancer-related fatigue have been performed. The methods of fatigue assessment were highly variable. Exercise programs show promise to prevent or treat fatigue in some subsets of cancer patients, and the use of epoetin alfa for correction of anemia has been shown to ameliorate fatigue. The number of subjects in the treatment trials was small and their methodologic quality was inconsistent.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Exercise Therapy; Fatigue; Humans; Neoplasms; Palliative Care; Radiotherapy; Randomized Controlled Trials as Topic; Recombinant Proteins

Despite the availability of highly active antiretroviral therapy and the resulting reduction in severe anemia associated with HIV infection, epoetin alfa has continued to play an important role in the management of HIV-infected patients. Mild-to-moderate anemia remains common, and its correction with epoetin alfa has resulted in significant improvements in quality of life, physical functioning, and possibly prolongation of survival. New research has demonstrated that epoetin alfa may have therapeutic potential beyond its ability to stimulate erythropoiesis due to its neuroprotective and antiapoptotic properties. Current and future research will further clarify the role of epoetin alfa in the clinical management of the HIV-infected population.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; HIV Infections; Humans; Recombinant Proteins; Treatment Outcome

Anemia in patients with cancer causes fatigue, weakness, and impaired concentration, negatively impacting quality of life (QOL). In clinical trials involving patients with cancer who had varied characteristics, it has been shown that epoetin alfa treatment increased hemoglobin levels and improved QOL. A systematic review and metaanalysis of data from those trials was conducted to summarize existing knowledge on the role of epoetin alfa in improving QOL for anemic patients with cancer.. The Cochrane Library and other data bases were searched for published and unpublished, randomized/controlled and single-arm studies that included > or = 20 patients with cancer per arm, epoetin alfa treatment, and QOL assessment by Cancer Linear Assessment Score (CLAS), Functional Assessment of Cancer Therapy (FACT) scale, Eastern Cooperative Oncology Group (ECOG) scale, and/or Medical Outcomes Study Short-Form 36 (SF-36) scale.. Among 11,459 patients from 23 trials, epoetin alfa and control cohorts were indistinguishable (with regard to demographic, clinical, QOL variables) at baseline. Epoetin alfa improved CLAS (20-25%), FACT-Fatigue (17%), and FACT-Anemia (12%) scores (P = 0.05). ECOG scores worsened for control cohorts (P = 0.05); epoetin alfa cohorts remained unchanged. Four of the SF-36 subscales, Physical Function, Role Physical, Vitality, and Social Function, improved with epoetin alfa (P = 0.05). Results adjusted for confounding factors remained consistent.. This metaanalysis confirmed that epoetin alfa improves QOL significantly in patients with cancer, emphasizing the need to manage anemia in this population.

Topics: Anemia; Case-Control Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins

Hematologic abnormalities such as anemia, neutropenia, and thrombocytopenia are common during combination therapy with pegylated (or standard) interferon and ribavirin for chronic hepatitis C. Ribavirin-induced hemolytic anemia is a common cause of dose reduction or discontinuation. Bone marrow suppression also contributes to the anemia and is the predominant mechanism for interferon-induced neutropenia and thrombocytopenia. Although dose reduction or discontinuation of combination therapy can reverse these abnormalities, they may reduce virologic response. Hematopoietic growth factors may provide a useful alternative for managing these hematologic side effects without reducing the optimal dose of the combination antiviral regimen. Treatment of anemia also may improve patients' health-related quality of life and their adherence to combination antiviral therapy. The impact of growth factors on sustained virologic response and their cost-effectiveness in patients with chronic hepatitis C need further assessment.

Topics: Anemia; Antiviral Agents; Clinical Trials as Topic; Darbepoetin alfa; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Interferons; Interleukin-11; Neutropenia; Patient Compliance; Polyethylene Glycols; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Ribavirin; Thrombocytopenia

Anaemia develops in most patients undergoing cancer therapy and invariably induces fatigue, which is a major determinant of QOL. Blood transfusions are reserved for patients with severe anaemia, since blood is a scarce resource and provides a short-lived benefit. Epoetins are recombinant proteins capable of alleviating therapy-related anaemia in 40-60% of cancer patients. The number of patients needed to be treated with epoetins to avoid the transfusion of one unit of blood ranges from 2.6 to 5.2; however, the absolute risk reduction depends on patients' characteristics and dose-escalation. The ratio between acquisition costs of epoetins and blood transfusion requirement is very high; thus, many thousands of dollars needs to be spent on epoetins to save 1 blood unit. Despite this, epoetins have been widely adopted by industrialised countries, where cancer patients are about 2% of the total population. The resulting budget impact of epoetins can be calculated at about 10% of the overall direct cost for cancer care, and it is expected to continue growing by about 20% each year, due to the expanding cancer population and the intensification of cancer therapies. The economic burden of epoetins needs to be weighed against the improvement of patients' QOL and society's willingness to pay for a non-life-saving therapy. All published economic evaluations of epoetins invariably report that this supportive therapy is not cost effective. Society should be made aware of the opportunity cost of treatments and should be allowed to elicit preferences for healthcare interventions and prioritisation criteria. In the near future we expect that a wider range of epoetins, drug patent expiry, a more appropriate patient selection criteria and an improved dosage schedule may help increase the efficiency of cancer-related anaemia management.

Topics: Anemia; Cost-Benefit Analysis; Darbepoetin alfa; Drug Administration Schedule; Drug Costs; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Iron; Iron Deficiencies; Neoplasms; Recombinant Proteins

Anemia is a reduction in the oxygen-carrying capacity of red blood cells that results in a variety of symptoms, including dyspnea, headaches, light-headedness, and fatigue. Although anemia has been associated with reduced health-related quality of life (HRQoL), its treatment has not yet been consistently shown to improve HRQoL.. This systematic review of the literature was conducted to determine whether the treatment of anemia improves HRQoL domains, regardless of the type of underlying disease.. Data for this review were drawn from the clinical trial databases from 2 previous systematic literature reviews of erythropoiesis-stimulating protein treatment for renal insufficiency- and cancer-related anemia, both spanning the period January 1, 1980, through December 31, 2001. MEDLINE, Cancerlit, and Current Contents/Clinical Medicine were searched using the combined terms erythropoietin, kidney failure, neoplasms, and anemia. The reference lists of all identified articles were searched manually for additional relevant papers. The review included prospective studies that reported both HRQoL and hematocrit (Hct) in patients with cancer or renal insufficiency who received treatment for anemia with an erythropoiesis-stimulating protein. HRQoL was categorized by domain (overall, energy/fatigue, physical, activity); changes in HRQoL domains were expressed as effect sizes and meta-analyzed, as were correlation coefficients. The effects on HRQoL of dropout rate, study duration, baseline Hct, and change in Hct were examined in meta-regression analyses.. Sixteen studies each were identified in patients with renal insufficiency (N = 2253) and patients with cancer (N = 10,695). The treated groups included 11,710 patients, and the control groups included 1238 patients. The baseline Hct in all treated groups averaged 26.0%: 28.3% in the group with cancer and 24.4% in the group with renal insufficiency. The mean improvement in Hct from baseline to the end of treatment was 8.3% (range, 1.0%-16.5%) in treated patients and 1.0% (range, 0.0%-3.3%) in controls. The Hct changes were similar in treated patients with cancer and treated patients with renal insufficiency, as was the HRQoL effect size (0.43). Dropout rate and study duration were not significant predictors of HRQoL changes, but change in Hct was a significant predictor in both conditions. Meta-analysis of the correlation coefficients, adjusting for HRQoL domains, showed a consistent and significant positive correlation between change in Hct and change in HRQoL (P < 0.001).. The consistency in both direction and magnitude of effect across many studies and thousands of patients supports the hypothesis that treatment of anemia with erythropoiesis-stimulating protein improves selected HRQoL domains in patients with renal insufficiency- or cancer-related anemia.

Topics: Anemia; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematocrit; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Renal Insufficiency; Treatment Outcome

Documentation of anemia-related assessments, interventions, and outcomes is an integral component of proper anemia management for patients with ESRD. In addition to promoting vital communication among medical professionals, documentation helps fulfill regulatory, legal, and payer reimbursement requirements, thereby ensuring that nursing contributions to patient well-being are recognized and that access to care is preserved.

Topics: Anemia; Continuity of Patient Care; Documentation; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Nurse's Role; Physician's Role; Practice Guidelines as Topic; Recombinant Proteins

Despite therapeutic improvements and ongoing efforts to develop more efficacious therapies, the majority of lung cancer patients face a poor prognosis. Therefore, the primary goal of current treatment is palliation, improvement and maintenance of quality of life (QOL), and (modest) prolongation of survival. Anemia frequently occurs in lung cancer patients and has been associated with decreased QOL, impaired treatment outcomes, and shortened survival time. Furthermore, anemia is a causative factor of tumor hypoxia, which compromises the efficacy of chemotherapy and radiotherapy. Thus, correction of even mild anemia seems to have a beneficial effect on QOL and cancer treatment outcomes. The current article describes the basis and mechanism for the use of recombinant human erythropoietin (rHuEPO, epoetin alfa), a molecular targeted therapy, for the treatment of cancer-related anemia, with a focus on lung cancer. Epoetin alfa has proven efficacy and safety in correcting anemia and improving QOL based on numerous clinical studies and over a decade of clinical practice. In addition, emerging data show that epoetin alfa may offer potential benefits beyond treating anemia, specifically in terms of treatment outcomes and cognitive function. Future research needs to be conducted to explore the potential for epoetin alfa to improve survival time in lung cancer patients.

Topics: Anemia; Clinical Trials as Topic; Cognition; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Lung Neoplasms; Palliative Care; Quality of Life; Recombinant Proteins; Survival Analysis; Treatment Outcome

Anemia has been reported in approximately 40%-70% of patients with hematologic malignancies, with severity depending on the type and stage of disease and whether the patient has received myelosuppressive chemotherapy. Growing evidence supports the role of epoetin alfa in correcting anemia and improving quality of life (QOL) in patients with hematologic malignancies. Clinical practice guidelines recommend the use of epoetin alfa in patients with cancer-related anemia (including patients with hematologic malignancies) and hemoglobin levels < or =10 g/dL. Epoetin alfa treatment is optional for patients with cancer-related anemia and hemoglobin levels>10 g/dL and <12 g/dL, depending on clinical circumstances. A prospective, open-label, randomized trial evaluating hematologic response, transfusion use, and QOL after immediate or delayed epoetin alfa treatment in mildly anemic patients (hemoglobin< or =12 g/dL) undergoing chemotherapy for chronic lymphocytic leukemia, multiple myeloma, or lymphoma was recently completed. Study objectives included determining any correlation between changes in hemoglobin level and QOL and assessing any correlation between QOL measures and health care resource use. Interim results suggest that epoetin alfa treatment in patients with hematologic cancers and hemoglobin< or =12 g/dL who are receiving chemotherapy increases hemoglobin, functional capacity, well-being, work and productivity, and health resource use. Further evaluation of alternative epoetin alfa dosing schedules and use of epoetin alfa in treating anemia in patients with specific hematologic malignancies is ongoing.

Topics: Anemia; Clinical Trials as Topic; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Hematologic Neoplasms; Hemoglobins; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Linear Models; Multiple Myeloma; Myelodysplastic Syndromes; Quality of Life; Random Allocation; Recombinant Proteins

Multiple myeloma (MM) is commonly associated with anemia. Several causes have been implicated, but anemia of chronic disease with inadequate erythropoietin (EPO) production related to the inflammatory cytokines appears to be of utmost importance. Interleukin-1 and tumor necrosis factor are capable of suppressing erythropoiesis. Anemia has broad implications. First, the low hemoglobin and hematocrit are associated with poor quality of life and performance and affect daily activity. Second, anemia has an impact on the cardiovascular system. Considering that most MM patients are elderly, this may be even more important. Anemia has been shown to induce or aggravate hypoxia and ischemic complications. Third, anemia has been shown to be a poor prognostic factor in MM. Traditionally, patients with symptomatic anemia were treated with red blood cell transfusions as needed. The introduction of epoetin alfa and epoetin beta into clinical practice opened new avenues to these patients. The administration of epoetins to patients with MM and anemia have been shown to be very useful. Several studies in more than 1000 patients have demonstrated a high response rate (range, 25%-85%; mean, 60%). This response is characterized by a significant increase of hemoglobin, hematocrit, and the number of red blood cells together with a reduction in the blood transfusion requirements. This is also associated with an improved quality of life. Although there is no complete agreement about the role of pretreatment serum EPO levels, many investigators believe that relatively low levels may help in predicting response, thereby limiting the number of potential candidates to receive this expensive therapy. The epoetins are safe and well tolerated with minimal toxicity; however, some concern has been recently raised regarding several dozen patients who developed pure red cell aplasia while on epoetin therapy. However, this adverse effect appears to be extremely rare. Recent data suggest that EPO has additional biologic effects, such as longer-than-expected survival in patients with MM. This observation is further supported by animal studies, demonstrating an antimyeloma effect of EPO in mice models. This effect has been shown to be immune mediated. If these exciting data are confirmed in future clinical trials, this may have significant implications on the treatment of MM.

Topics: Anemia; Animals; Cytokines; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hemoglobins; Humans; Hypoxia; Mice; Mice, Inbred BALB C; Multiple Myeloma; Prognosis; Quality of Life; Recombinant Proteins; Time Factors

Anaemia in cancer patients is multifactorial. Anaemia of chronic disease due to the effects of cancer, as well as side effects of cancer treatment, are important factors. The impact of anaemia on the quality of life and social function of cancer patients has recently become more acknowledged. The traditional treatment for chemotherapy-induced anaemia (CIA) has been the use of red blood cell transfusions, with only short-lived effects and all their inherent risks. The finding of deficiency in erythropoietin, the endogenous hormone responsible for the production and maintenance of red blood cells in these patients, was the basis for the therapeutic development of erythropoietic proteins. With the introduction of epoetins (recombinant forms of human erythropoietin) in oncology and more recently, the novel long-acting darbepoetin alpha, physicians gained new pharmacotherapeutic approaches to treat CIA. Several forms of erythropoietic proteins are available in various regions of the world. Their characteristics, clinical evidence for use, guidelines for clinical administration and their safety are described in this review.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Recombinant human erythropoietin (epoetin alfa) has proven beneficial for the treatment of various anemias. The mechanism of action of endogenous erythropoietin and the therapeutic use of epoetin alfa to stimulate red blood cell production and improve the quality of life in cancer patients are reviewed here. Epoetin alfa may also attenuate the cognitive dysfunction associated with cancer therapy. Interestingly, functional endogenous erythropoietin receptor signaling pathways have been demonstrated in numerous nonerythropoietic tissues. Of particular importance, epoetin alfa confers neurotrophic and neuroprotective effects in cultured neurons and in several animal models for neurologic disease. In one clinical trial, epoetin alfa appeared to limit functional and histologic damage in patients with stroke. Therefore, in cancer patients receiving chemotherapy, the beneficial effects of epoetin alfa could be mediated not only through enhanced erythrocyte production but also via direct effects on the nervous system. Further investigation into the nonerythropoietic effects of epoetin alfa could broaden its clinical utility for patients with cancer and also provide new therapies for various neurologic disorders.

Topics: Anemia; Apoptosis; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Neoplasms; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Signal Transduction

To describe the management of fatigue and anemia in patients with cancer.. Published literature and clinical experience.. Anemia is a common cause of cancer-related fatigue. Epoetin alfa increases hemoglobin, decreases transfusion requirements, and improves energy and quality of life in patients with cancer-related anemia. Nonpharmacologic treatment options include exercise, nutrition optimization, and psychosocial interventions. Effective management of fatigue improves overall cancer treatment, quality of life, and functional status.. Fatigue and anemia are commonly undertreated complications of cancer and its treatment. Oncology nurses play a key role in identifying and managing these conditions.

Topics: Activities of Daily Living; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Humans; Male; Neoplasms; Nursing Assessment; Nursing Methodology Research; Oncology Nursing; Patient Care Planning; Quality of Life; Recombinant Proteins

Chemotherapy-associated cognitive dysfunction occurs in a subset of patients treated with adjuvant chemotherapy. Recent data suggest that development of chemotherapy-related anemia predisposes patients to cognitive dysfunction. Endogenous erythropoietin (EPO) is well recognized for its central role in erythropoiesis, and recombinant human EPO (epoetin alfa) is established as a safe and effective treatment for chemotherapy-related anemia. Treatment with epoetin alfa also improved health-related quality of life in anemic cancer patients undergoing chemotherapy, and several controlled studies have documented increases in quality-of-life scores correlated with increases in hemoglobin. Erythropoietin also plays a role in neuroprotection, presumably by activation of antiapoptotic genes. Erythropoietin and its receptor are expressed in neural cells of the human brain, and their expression is upregulated after hypoxic or ischemic injury. In animal models, systemic administration of epoetin alfa protects against such neural injury. Ongoing and future studies will determine whether epoetin alfa can provide neuroprotection with respect to the development of cognitive dysfunction in patients undergoing adjuvant chemotherapy treatment for breast cancer.

Topics: Anemia; Animals; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cognition Disorders; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Quality of Life; Rats; Recombinant Proteins

Myelosuppression associated with cancer chemotherapy may lead to neutropenia, anemia, or both, resulting in an increased risk for infection, fatigue, diminished quality of life, and reduced survival. In addition, neutropenia specifically has been shown to result in dose reductions, treatment delays, or both in subsequent chemotherapy cycles. Hematopoietic growth factors have been used effectively as supportive therapy to reduce chemotherapy-associated neutropenia and anemia. New preparations have the potential to improve treatment outcome dramatically. Results from recently reported studies indicate that patients at risk for neutropenia can be safely and effectively treated with pegfilgrastim once per chemotherapy cycle, and that those with anemia can be managed with weekly or biweekly darbepoetin alfa therapy. These new treatments have the potential to reduce the morbidity and mortality associated with opportunistic infections, decrease the requirement for potentially dangerous blood transfusions, and improve the quality of life for patients undergoing cancer chemotherapy. The longer dosing intervals offered by these new preparations may decrease healthcare expenses and enhance patient adherence.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Neutropenia; Polyethylene Glycols; Recombinant Proteins

Cancer-related anemia often develops from the infiltration of marrow by malignant cells, impaired hemoglobin (Hb) production related to chemotherapy or radiation therapy, iron deficiency, or low endogenous erythropoietin levels. Patients with cancer-related anemia may experience cognitive dysfunction including decreased mental alertness, poor concentration, and memory problems. Anemia-mediated cerebral hypoxia may cause symptoms such as headache, vertigo, tinnitus, and dizziness. These symptoms often are exacerbated in the elderly patient with cancer and related to underlying low Hb concentrations. Restoring Hb levels via the administration of iron supplements, blood transfusions, or, more recently, erythropoiesis-stimulating therapy (epoetin alfa) results in significant improvement of cognitive function. The use of epoetin alfa as a treatment option for patients with chemotherapy-associated anemia and an Hb concentration less than 10 g/dL has been recommended by the American Society of Clinical Oncology and the American Society of Hematology. Erythropoiesis-stimulating therapies are a promising treatment option for cancer-related anemia that may improve cognitive function and quality of life for patients with cancer.

Topics: Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Cognition Disorders; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Neoplasms; Recombinant Proteins

Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients often develop anemia due to the disease process and effects from disease therapy. Blood transfusion, the established treatment, has an immediate effect in improving patients' hemoglobin levels. However, this effect is transient and transfusion is associated with several risks, including infections and mild to life-threatening immunologic reactions. A newer option is recombinant human erythropoietin (epoetin); a biological treatment that leads to increased hemoglobin levels over an extended time without the risks of blood transfusion. Extensive evidence has shown that epoetin is effective in the treatment of cancer-associated anemia. An international expert panel met to develop treatment recommendations for the use of epoetin in MM and CLL patients. Based on the available data, it is recommended that treatment be initiated only after other possible causes of anemia are eliminated. Epoetin should be administered to any patient with hemoglobin < or=10 g/dl. Patients with hemoglobin 10-12 g/dl should receive epoetin if they suffer from significant symptoms of anemia and/or have progressively decreasing hemoglobin values. Dosage should be initiated at 10 000 IU three times/week or 40 000 IU once/week and be titrated to maintain hemoglobin at 12 g/dl. Nonresponsive patients (<1 g/dl increase over four weeks) may have their dose increased to 20 000 IU three times/week or 60 000 IU once/week, respectively. Epoetin treatment should be discontinued if there is no response to the increased dosage, or hemoglobin >14 g/dl. Treatment should resume for patients who exceed 14 g/dl, at a reduced dosage, if their hemoglobin falls below 12 g/dl.

Topics: Anemia; Disease Management; Epoetin Alfa; Erythropoietin; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma; Practice Guidelines as Topic; Recombinant Proteins

Novel approaches to anemia associated with cancer and chemotherapy are reviewed. Anemia in cancer patients is usually related to treatment with antineoplastic agents or to the disease itself. The normal concentration of endogenous erythropoietin ranges from 0.1 to 0.2 microU/mL and may increase to 2-10 microU/mL in patients with severe anemia. Many cancer patients with anemia do not have an increase in erythropoietin levels, however. Recombinant human erythropoietin (epoetin alfa), the standard for treating anemia caused by chronic renal failure, is also used to treat cancer chemotherapy-related anemia. It resolves anemia, decreases the need for transfusions, and may improve a patient's quality of life. A newer erythropoiesis-stimulating protein, darbepoetin alfa, was initially evaluated in patients with chronic renal disease. In patients who had never taken epoetin alfa, darbepoetin alfa was able to achieve a hemoglobin concentration of 11 g/dL by four weeks in most patients, and 97% of patients maintained on epoetin alfa were successfully switched to the other drug. Similar positive results were achieved in patients with solid tumors receiving chemotherapy, patients with anemia of chronic disease associated with cancer, and patients with lymphoproliferative malignancies. Darbepoetin alfa has a longer half-life than epoetin alfa, enabling less frequent administration. No difference in toxicity between the two agents has been reported. Epoetin alfa and darbepoetin alfa are effective in the treatment of anemia in patients with cancer.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Half-Life; Humans; Kidney Failure, Chronic; Recombinant Proteins

Children with cancer frequently develop anemia both from the disease and from chemo- and radiotherapy. Considered a manageable complication, anemia is often not treated until it becomes severe, i.e., hemoglobin (Hb) level

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Child; Child, Preschool; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Infant; Infant, Newborn; Male; Neoplasms; Recombinant Proteins; Retrospective Studies; Risk Assessment; Treatment Outcome

Numerous reports on recombinant human erythropoietin (rHuEPO, epoetin alfa) treatment of cancer-related anemia in adult patients have been published to date. These have shown that epoetin increases hemoglobin levels, significantly ameliorates symptoms of anemia, and improves adult patients' quality of life. Unfortunately, less is known about the impact of epoetin on anemia in pediatric cancer patients.. It is the objective of this review to summarize and analyze data of clinical trials of epoetin treatment of anemia in pediatric cancer patients.. A total of 15 studies were reviewed; eight were considered for detailed analysis and demonstrated important variabilities in study methods. Four of the eight were controlled, randomized trials and four were open label.. These studies suggested an overall beneficial effect of epoetin alfa for treating anemia in children with cancer. Three large, multicenter clinical trials of the efficacy and safety of epoetin alfa in anemic children with cancer are currently underway, one in Europe and two in North America.

Topics: Anemia; Child; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Medical Oncology; Multicenter Studies as Topic; Neoplasms; Pediatrics; Randomized Controlled Trials as Topic; Recombinant Proteins

Anemia of chronic kidney disease (CKD) results primarily from a deficiency of the hormone erythropoietin. Treatment of anemia in the early stages of CKD is essential to reduce the risk of developing anemia-associated complications and to improve health-related quality of life. Treatment with recombinant human erythropoietin (r-HuEPO, epoetin alfa) can correct erythropoietin deficiency and increase red blood cell production, but the short half-life of r-HuEPO necessitates frequent injections. Reducing the frequency of administration has potential benefits for both patients and health care providers. Darbepoetin alfa is a new erythropoietic protein with greater biologic activity and a longer dosing interval than those of r-HuEPO. It has been shown to be effective when administered once/week and once every 2, 3, or 4 weeks, and is well tolerated. With the ability to simplify anemia management by allowing less frequent dosing, darbepoetin alfa offers an effective alternative to r-HuEPO for the treatment of anemia of CKD.

Topics: Anemia; Animals; Clinical Trials as Topic; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Recombinant Proteins

Cancer-associated anemia is common and has many causes, including the effects of the underlying disease and cancer treatment. The effect of anemia on patients with cancer was not appreciated fully until relatively recently. Several well-designed studies have demonstrated the relationship between anemia and fatigue, and the effect of fatigue on quality of life. These data have resulted in a greater awareness of anemia in cancer and have increased the use of recombinant human erythropoietin (r-HuEPO, epoetin alfa) therapy for the treatment of anemia. Recombinant HuEPO produces a hemoglobin response in 50-60% of patients with cancer; however, to obtain this response rate, frequent dosing is required. Darbepoetin alfa, a recently developed erythropoietic protein, has a longer half-life than that of r-HuEPO, enabling less frequent dosing, and has a greater in vivo activity. In studies of patients with cancer who develop anemia, darbepoetin alfa has proved to be well tolerated and effective, and its advantages make it a potential improved treatment option for anemia in these patients.

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Recombinant human erythropoietin (r-HuEPO, epoetin alfa), is an established and effective treatment for anemia associated with both chronic kidney disease (CKD) and cancer and has improved the management of anemia over alternatives such as transfusion. Darbepoetin alfa is a new erythropoietic agent with a 3-fold longer half-life and increased in vivo potency relative to r-HuEPO. These properties allow patients to be treated with longer dosing intervals than with r-HuEPO. Relative potency between r-HuEPO and darbepoetin alfa is not a fixed relationship but is dependent on several factors. Clinical study results suggest that greater relative potency differences are seen between r-HuEPO and darbepoetin alfa when the dosing intervals are longer and when r-HuEPO dose requirements are higher. Although 200 U of r-HuEPO contains the same peptide mass as 1 microg of darbepoetin alfa, a fixed ratio of 200:1 does not necessarily predict an appropriate dose conversion between the two drugs across the entire spectrum of dose ranges. When converting patients with CKD from r-HuEPO to darbepoetin alfa, dosing should be based on relevant clinical data. Appropriate guidance for conversion of patients with CKD from r-HuEPO to darbepoetin alfa is provided in the approved United States package insert for darbepoetin alfa. In patients who are prescribed darbepoetin alfa, either by conversion from r-HuEPO or as de novo treatment, therapy should begin according to recommendations in the package insert, after which, doses should be titrated individually according to each patient's hemoglobin response. Dosing data from oncology clinical studies, although not necessarily applicable to CKD, indicate similar potency ratios between r-HuEPO and darbepoetin alfa, and in addition affirm the finding that, as the interval between doses of darbepoetin alfa is increased, hemoglobin response is maintained.

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Drug Administration Schedule; Drug Labeling; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Intravenous; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins; Therapeutic Equivalency

Anemia in cancer patients is associated with a decline in energy levels, activity levels, and quality of life, and these variables improve when hemoglobin levels rise. Importantly, the impact of improved hemoglobin levels on response to chemotherapy, radiation therapy, and survival time is under study. This line of research follows favorable preliminary data in clinical studies suggesting improved treatment outcomes with reversal of anemia. It is estimated that there are 10 million people in the United States with cancer. Of the 1.3 million cancer patients who are anemic with hemoglobin levels less than 12 g/dL, about 800,000 are receiving chemotherapy and 500,000 are not. The predominant treatable cause of anemia in these patients is a relative lack of erythropoietin; overall, only 20% of anemic cancer patients receive a trial of erythropoietic therapy. About one-fourth (26%) of patients whose hemoglobin is less than 12 g/dL and who are receiving chemotherapy for cancer are currently receiving erythropoietic therapy. A review of the patients in our oncology practice revealed that 37% were anemic (hemoglobin < 12 g/dL) prior to chemotherapy, and an additional 41% became anemic during chemotherapy. Overall, 63% of our cancer patients on chemotherapy received erythropoietin; 6% of these patients received red cell transfusions. Only 7% of our patients had a hemoglobin level < 10 g/dL before chemotherapy; overall, 80% of our patients maintained hemoglobin levels > or = 10 g/dL at all times. Barriers to the use of erythropoietic agents include cost and reimbursement issues, inconvenience of frequent injections, limitations in efficacy, and indication restrictions. An understanding of the importance of anemia and newer agents requiring less frequent dosing, such as darbepoetin alfa (Aranesp), may help physicians and patients overcome some of these barriers.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; United States

Anemia is prevalent among cancer patients with hematologic malignancies, with fatigue and weakness, major symptoms of anemia, contributing to diminished quality of life (QOL). Data from several randomized, placebo-controlled clinical trials and three large community-based studies in patients with hematologic malignancies indicate that recombinant human erythropoietin (r-HuEPO, epoetin alfa) can correct anemia, reduce transfusion requirements, and improve QOL. Moreover, a positive relationship has been found between increased hemoglobin (Hb) levels and improvements in QOL assessments, regardless of disease state, with the greatest incremental improvement occurring when Hb increases from 11 g/dL to 12 g/dL (range, 11 to 13 g/dL). This suggests that patients with mild-to-moderate anemia may achieve the greatest QOL benefit from epoetin alfa therapy. Evidence from community-based studies suggests that epoetin alfa administered once weekly has a similar safety and efficacy profile as three-times-weekly administration. Further research is ongoing with less frequent dosing regimens. The beneficial effects of epoetin alfa therapy have been reported in studies involving patients with chronic lymphocytic leukemia (CLL), multiple myeloma, and lymphomas. Evidence also exists that epoetin alfa can benefit patients with myelodysplastic syndromes (MDS), although these results have not been as impressive. Combining epoetin alfa with other cytokine growth factors may confer some additional benefit in these patients, but more rigorous investigation is required.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematologic Neoplasms; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma; Recombinant Proteins; Treatment Outcome

As the antitumor activity of radiation is mediated via its interaction with oxygen to form labile free radicals, the intratumoral oxygen level has an important influence on the ability of radiation therapy to kill malignant cells. By decreasing the oxygen-carrying capacity of the blood, anemia may result in tumor hypoxia and may have a negative influence on the outcome of radiotherapy for various malignancies, even for small tumors not normally assumed to be hypoxic. In addition, anemia also has a negative effect on the quality of life of cancer patients, as evidenced by worsening fatigue. As a high proportion (about 50%) of cancer patients undergoing radiotherapy are anemic prior to or during treatment, strategies to correct anemia and/or the resultant tumor hypoxia are increasingly being considered an important component of treatment. In particular, epoetin alfa (recombinant human erythropoietin), which has proved an effective and well-tolerated means of raising hemoglobin levels in anemic patients receiving radiotherapy, potentially could reverse the negative prognostic influence of a low hemoglobin in patients with certain malignancies. Radiation oncologists need to be aware of the possibility of anemia in cancer patients undergoing radiotherapy so that timely intervention can be instituted whenever anemia is diagnosed.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Peripheral Nervous System Diseases; Predictive Value of Tests; Prevalence; Prognosis; Quality of Life; Radiotherapy; Recombinant Proteins; Survival Analysis; Treatment Outcome

Although the association between low hemoglobin levels and poorer outcomes in radiation oncology has long been recognized, anemia is often overlooked and untreated. However, a growing body of clinical evidence now indicates that low hemoglobin levels during radiation treatment are associated with decreased response and survival following radiotherapy. For example, a large Canadian retrospective study in patients receiving radical radiotherapy for cervical cancer showed that the 5-year survival rate was 19% higher in those whose hemoglobin during radiation treatment was =12 g/dl compared to those with levels <12 g/dl. The data suggest that clinical trials need to be performed to determine whether increasing hemoglobin levels leads to improved local control and survival. The mechanism by which low hemoglobin levels could cause poorer outcomes is not well understood and needs further elucidation. It is postulated that lower hemoglobin levels resulting in decreased oxygen carrying capacity may lead to increased tumor hypoxia, radiation resistance and increased tumor angiogenesis. The interrelationship of low hemoglobin levels, hypoxia, tumor angiogenesis and survival is explored in this article.

Topics: Anemia; Cell Hypoxia; Chemotherapy, Adjuvant; Epoetin Alfa; Erythropoietin; Female; Head and Neck Neoplasms; Hematinics; Hemoglobins; Humans; Neoplasms; Neovascularization, Pathologic; Radiotherapy, Adjuvant; Recombinant Proteins; Survival Analysis; Survival Rate; Uterine Cervical Neoplasms

Chronic anemia of variable severity occurs in more than two-thirds of patients with multiple myeloma (MM) as a consequence of the B cell malignancy. Its pathogenesis is multifactorial. Besides the altered inflammatory cytokine network, other events are held responsible, namely persistent defect of erythropoietin due to the kidney failure, shortening of red cell survival, accumulation of the serum monoclonal component and platelet dysfunction. Our recent studies have demonstrated that excessive erythroblast apoptosis promoted by myeloma cells drives the appearance of anemia, in particular in patients with severely progressive disease. A number of clinical trials have provided evidence for the effectiveness of recombinant human erythropoietin (rHuEPO-alpha: epoetin alpha) in improving the deregulated erythropoiesis in MM, since it acts as a major erythroid growth factor by exerting a specific anti-apoptotic effect. In the majority of these studies, the long-term treatment of MM-associated anemia with rHuEPO-alpha induced a significant improvement of erythropoiesis, as shown by a stable increase of hemoglobin values (> or = 2g/dL) and reduction of transfusion requirements. In a recent trial which included both a double-blind and an open-label phase, we have documented that rHuEPO-alpha induces a stable improvement of anemia in more than 75% of patients and a significant decrease of fatigue, with an overall recovery of the quality of life. Patients receiving a placebo also achieved similar results in the open-label phase, when they were switched to rHuEPO-alpha.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Blood Transfusion; Cell Differentiation; Chronic Disease; Clinical Trials as Topic; Cytokines; Epoetin Alfa; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Humans; Multiple Myeloma; Quality of Life; Recombinant Proteins; Treatment Outcome

Anaemia occurs in a significant number of patients with cancer, and is associated with symptoms of fatigue, dizziness, headache and decreased health-related quality of life. Clinical trials have demonstrated the ability of epoetin alfa to increase haemoglobin concentrations and reduce transfusion requirements in patients with cancer. Data from three large, open-label, community-based trials of >7000 patients, as well as a series of smaller, randomized, placebo-controlled studies, have confirmed the efficacy of treatment with epoetin alfa in patients undergoing chemotherapy. In two of the community-based studies (>2000 patients in each), patients undergoing chemotherapy received epoetin alfa, 150-300 IU/kg or 10,000-20,000 IU, three times weekly. Significant (P<0.01) increases in haemoglobin concentrations and reductions in transfusion rates were seen in both studies. Significant improvements in quality of life were also reported, as measured by the Linear Analogue Scale Assessment and the Functional Assessment of Cancer Therapy-Anaemia. Importantly, the increases in quality of life were independent of tumour response. These findings were also observed in randomized, placebo-controlled studies. The third study, in approximately 3000 patients, evaluated the efficacy of once-weekly dosing, which significantly (P<0.01) increased haemoglobin concentrations, reduced transfusion requirements and improved quality of life. Greater increases in haemoglobin concentration were associated with greater improvements in quality-of-life scores. The safety and efficacy profile of the once-weekly regimen was comparable with that of the three times weekly regimen. Maintaining optimal quality of life, while achieving tumour stabilization or regression, is essential to the successful management of patients with cancer. Epoetin alfa has been shown to increase haemoglobin concentration, decrease transfusion requirements and increase quality of life. Given the frequency of adverse sequelae associated with anaemia, its aggressive management should become an integral and routine part of cancer treatment.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Over the past decade an increasing number of studies have supported the use of recombinant human erythropoietin (epoetin) in cancer patients, suggesting that it improves haemoglobin concentrations for some. There is also evidence that this treatment may lead to improvement in quality of life for cancer patients. This systematic review examines the issue. We identified and critically reviewed 13 trials. Although some of the results indicate that epoetin has positive effects on quality of life, methodological limitations inherent in most of the studies hamper interpretation of data. Evidence from this review suggests that more robust designs are required to show any significant quality-of-life benefits for cancer patients undergoing epoetin treatment.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Controlled Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Subcutaneous; Male; Neoplasms; Quality of Life; Recombinant Proteins; Sensitivity and Specificity

Anemia is the most commonly encountered hematologic abnormality in human immunodeficiency virus (HIV)-positive patients, occurring with increasing frequency as the disease progresses. Several factors play a role in the development of anemia in patients with HIV, including chronic disease, opportunistic infections, and certain nutritional deficiencies. Despite the high prevalence of anemia in this population, the symptoms of anemia are frequently overlooked, although anemia can significantly affect a patient's ability to carry on even normal activities of daily living. Therefore, approaches--including the treatment of causative infections, discontinuation of certain drugs, or use of recombinant human erythropoietin (epoetin alfa)--aimed at increasing hemoglobin levels to normal or near-normal levels would be expected to improve quality of life (QOL). The purpose of this article is to describe the effects of anemia on QOL and to provide an overview of several studies showing that QOL improves with the alleviation of anemia.

Topics: Anemia; Antiretroviral Therapy, Highly Active; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; HIV Infections; Humans; Quality of Life; Recombinant Proteins

Three large observational cohort studies suggest that, after controlling for virus load and CD4 cell count, anemia is related to disease progression and survival in patients with human immunodeficiency virus (HIV) infection. Recovery from anemia has been linked to improved survival outcomes. Blood transfusion has been associated with accelerated disease progression and mortality in patients with HIV infection, and review of related literature suggests that the mechanism for negative transfusion-associated outcomes may be transfusion-related immunosuppression. Therefore, the use of transfusion should be restricted to patients with acute or severe anemia. Prescription of epoetin alfa has been associated with increased survival in an observational cohort among patients with HIV infection and anemia. In the absence of data from a clinical trial documenting the effect of treating anemia on survival, clinicians should consider non-transfusion options for management of anemia on the basis of clinical status and patient functional ability.

Topics: Anemia; Blood Transfusion; Disease Progression; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; HIV Infections; Humans; Quality of Life; Recombinant Proteins; Survival Analysis

Anemia is a frequent complication of cancer and its treatment. It often impairs the functional status of patients and results in decreased functional capacity and quality of life. Its etiologies are multiple, including chronic inflammation, hemorrhage, nutritional deficiencies, hemolysis, bone marrow suppression by chemotherapy, or infiltration by tumor. It can manifest as feelings of weariness, tiredness, muscular weakness, dysphoric mood, somnolence, or impaired cognitive functioning. In gynecologic patients, the incidence of anemia has been reported to be as high as 80% depending on chemotherapy regimen. Given the various consequences of a low hemoglobin level, the importance of increasing or maintaining hemoglobin levels and ameliorating the symptoms is apparent. Clinical studies have demonstrated that the administration of recombinant human erythropoietin (rHuEPO, epoetin alfa) is effective and safe in increasing hemoglobin levels and improving the overall quality of life in patients with gynecologic cancers undergoing chemotherapy. Therefore, epoetin alfa treatment should be considered in this patient population.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Genital Neoplasms, Female; Hematinics; Hemoglobins; Humans; Quality of Life; Recombinant Proteins

A Consensus Conference on the use of recombinant human erythropoietin (rHuEPO, epoetin alfa) in gynecologic tumors was held in Rome in March 1999, and an associated consensus paper has been published in Italian. The current paper updates several discussions that took place at the 1999 meeting concerning epoetin alfa treatment in breast, ovarian, and cervical cancers; the role of epoetin alfa in mobilizing progenitor hematopoietic cells; administration of epoetin alfa in combination with granulocyte colony-stimulating factor; and the effect of hemoglobin levels on outcome of radiation or chemoradiation treatment.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Female; Genital Neoplasms, Female; Granulocyte Colony-Stimulating Factor; Hematinics; Hematopoietic Stem Cell Mobilization; Hemoglobins; Humans; Ovarian Neoplasms; Quality of Life; Radiotherapy, Adjuvant; Recombinant Proteins; Uterine Cervical Neoplasms

Breast cancer patients undergoing therapeutic regimens of high-dose chemotherapy (HDCT) with circulating progenitor cell support often develop anemia. As a general consideration in the transplantation setting, red blood cell transfusions are normally required in patients who have passed the myeloablative phase after HDCT. In the initial 30-day period immediately following HDCT, the number of red blood cell units that are transfused will usually depend on a number of factors, including whether the transplantation was allogeneic or autologous. Observations and results from clinical studies have shown that the establishment of normal erythropoiesis varies depending on the source of the transplanted cells, resulting in different transfusion requirements. Several studies support the use of recombinant human erythropoietin (rHuEPO, epoetin alfa) after HDCT to ameliorate anemia and reduce transfusion requirements. Studies have also shown that administration of epoetin alfa prior to the myeloablative phase is an effective method for reducing red blood cell transfusion requirements in breast cancer patients receiving HDCT. Epoetin alfa in combination with other cytokines has been shown to positively affect the mobilization phase of hematopoietic progenitor cells for autografting. Furthermore, treatment with epoetin alfa could prove useful in bone marrow transplant recipients who experience delayed anemia. Recent studies that have addressed these topics in breast cancer indicate that, when used in the appropriate setting, epoetin alfa may play a role as a tool to decrease the need for red blood cell transfusion in patients undergoing HDCT plus autologous circulating progenitor cell support.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Bone Marrow Transplantation; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Hematinics; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Recombinant Proteins

During the past 40 years substantial progress has been made in the treatment of hematologic malignancies, particularly in some subgroups of patients. Today, cure is attainable for patients with Hodgkin's disease and a considerable proportion of patients with high-grade non-Hodgkin's lymphoma. Prognosis is improving in patients with acute promyelocytic leukemia and, to some extent, those with acute lymphoblastic and myeloid leukemias. However, the majority of patients who suffer from a hematologic malignancy live with incurable disease. In CLL, outside the setting of a clinical trial, it is advisable to postpone treatment until the manifestation of clinical symptoms. It is yet to be determined whether treatment strategies based on new prognostic parameters such as cytogenetics can change the course of disease. In indolent lymphomas, cure is not attainable for the vast majority of patients; the median survival of 9 to 10 years has remained unchanged for several decades. Nevertheless, there has been a dramatic change in therapeutic paradigms in the past few years. For the first time, with the use of new cytostatic drugs and recombinant monoclonal antibodies, it is possible to achieve molecular remissions. Whether this will translate into cure or prolonged survival is still to be determined. In Hodgkin's disease, which is curable when treated with radiotherapy, chemotherapy, or combined therapy, depending on the stage of disease, the focus of future studies must be on prevention of early relapse and on primary resistant disease, both of which present a very poor prognosis. Finally, regardless of underlying malignancy and prognosis, the preservation of quality of life is of major consideration in the setting of hematologic malignancies.

Topics: Anemia; Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Epoetin Alfa; Erythropoietin; Hematinics; Hodgkin Disease; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Prognosis; Quality of Life; Recombinant Proteins; Vidarabine

Anemia is a common complication in patients with hematologic malignancies, and is caused by a variety of mechanisms, including neoplastic cell infiltration into the bone marrow, hemolysis, nutritional deficiencies, and defects in erythropoiesis as a result of the disease itself or cytotoxic therapy. The anemia associated with multiple myeloma is caused by inadequate erythropoietin levels consequent to renal impairment and the effect of inflammatory cytokines. The degree of anemia can have prognostic importance, as is the case with multiple myeloma, or be a significant indicator of disease stage, as noted with chronic lymphocytic leukemia. Anemia results in fatigue, exhaustion, dizziness, headache, dyspnea, and decreased motivation, seriously affecting a patient's quality of life. Since anemia is so prevalent in hematologic malignancy patients, its treatment must be an integral part of disease management, to improve quality of life and to possibly increase potential survival. Clinical studies have shown that effectively treating anemia and increasing hemoglobin levels using recombinant human erythropoietin (rHuEPO, epoetin alfa) has a significant effect on transfusion requirements and quality of life.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Multiple Myeloma; Myelodysplastic Syndromes; Prognosis; Quality of Life; Recombinant Proteins; Survival Rate

Anemia is a common complication in patients with hematologic malignancies, with incidence rates ranging up to 63%. In myelodysplastic syndromes, anemia is an essential feature of the disease. The decrease in hemoglobin may lead to several symptoms such as fatigue, exhaustion, and impaired quality of life, and it may worsen prognosis. Before the introduction of recombinant human erythropoietin (rHuEPO, epoetin alfa), red blood cell transfusions were the traditional treatment for improvement of Hb levels. Transfusions, however, are associated with several adverse events and risks, have only transient effects, and have a limited capacity to ameliorate the symptoms of anemia. Epoetin alfa represents a physiologic treatment option, especially in the long-term treatment of cancer- and cancer treatment-associated anemia, and is well tolerated, with response rates as high as 80%. Epoetin alfa is less effective in the treatment of the anemia of myelodysplastic syndrome, but appears to be synergistic with granulocyte-colony stimulating factor. However, not every patient responds to epoetin alfa; to avoid unnecessary interventions and costs, predictors of response have been proposed. This article outlines the advantages and disadvantages of the two major treatment forms of anemia: transfusions and epoetin alfa. Representative studies on the efficacy of epoetin alfa in anemic patients with hematologic malignancies as well as models to predict response to epoetin alfa treatment are summarized.

Topics: Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Hematinics; Hematologic Neoplasms; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma; Myelodysplastic Syndromes; Prevalence; Recombinant Proteins

Epoetin alfa has been in use for over a decade to increase hemoglobin in patients with cancer who develop chemotherapy-associated anemia. Early placebo-controlled, randomized studies, as well as recent large, community-based trials in thousands of patients, have consistently shown recombinant human erythropoietin (rHuEPO, epoetin alfa) to be effective and safe in the treatment of chemotherapy-associated anemia. Patients experienced an improved quality of life (QOL) related to the magnitude of the hemoglobin increase. As measured by a Linear Analog Scale Assessment, mean energy level, ability to do daily activities, and overall QOL improved significantly in patients who received epoetin alfa. The improvement in QOL was similar when anemia-specific instruments (Functional Assessment of Cancer Therapy-Anemia) were used. A large community-based trial has demonstrated that the more convenient once-weekly dosing schedule resulted in good efficacy and safety profiles. A recent double-blind placebo-controlled study that compared the efficacy of epoetin alfa versus placebo in patients receiving nonplatinum-based chemotherapy has confirmed epoetin alfa's efficacy, safety, and beneficial QOL effects. These findings should challenge current anemia management practices and encourage aggressive treatment of anemia in cancer patients receiving chemotherapy.

Topics: Aged; Anemia; Antineoplastic Agents; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Adaptation, Physiological; Anemia; Cardiovascular System; Cognition Disorders; Drug Costs; Epoetin Alfa; Erythropoietin; Exercise; Heart Failure; Hematocrit; Hemodynamics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Iron; Kidney Failure, Chronic; Multicenter Studies as Topic; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Reference Values; Renal Dialysis; Risk; Thrombophilia; Treatment Outcome

Topics: Adult; Aged; Anemia; Child; Comorbidity; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Occupations; Peritoneal Dialysis; Physical Fitness; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Reference Values; Renal Dialysis; Thrombophilia; Treatment Outcome

Acute or chronic anemia, a common complication in cancer patients, is associated with the development of tumor hypoxia. It has been shown in several trials that decreased hemoglobin (Hb) levels inducing tumor hypoxia adversely impact radiotherapy or combined radiochemotherapy outcome. For example, pre- and post-treatment Hb levels can be predictive factors for the outcome of radiotherapy, locoregional tumor control, and survival. Two strategies have been established to correct cancer-related anemia and improve radiotherapy outcome: immediate increase of Hb levels with transfusions, or treatment with recombinant human erythropoietin (r-HuEPO, epoetin alfa), which slowly but steadily increases Hb levels to within normal range. As transfusions are associated with severe risks and adverse events, the use of epoetin alfa to treat pre-existing anemia or prevent therapy-induced anemia represents an attractive strategy. The ability of epoetin alfa to maintain or to increase Hb levels in patients undergoing radiotherapy or radiochemotherapy have been shown in several studies in different tumor types. In addition to improving the results of radiotherapy and radiochemotherapy, anemia intervention with epoetin alfa may impact overall survival.

Topics: Anemia; Cell Hypoxia; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Prognosis; Recombinant Proteins

Clinical trials and surveys have shown that a majority of patients with cancer have low hemoglobin levels as a result of the disease and/or treatment. Clinical trials also have shown that the impact of anemia may be more insidious and far-reaching than generally appreciated. Specifically, studies have shown that low hemoglobin levels have significant impact on treatment outcomes, including survival. The mechanisms by which treatment efficacy and survival are compromised have not been fully elucidated but may include cellular compromise (eg, impaired tumor oxygenation), or more general patient compromise (eg, decreased quality of life and treatment delivery). Recent studies have suggested that increasing hemoglobin levels with recombinant human erythropoietin (r-HuEPO, epoetin alfa) have resulted in better outcomes following radiotherapy, chemotherapy, and the combined-treatment modality.

Topics: Anemia; Cell Hypoxia; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Treatment Outcome

Hysterectomy is the second-most-common surgical procedure among premenopausal women. The conditions that lead to the need for a hysterectomy often are accompanied by chronic blood loss that can lead to anemia. Moreover, hysterectomy and myomectomy may result in significant blood loss, which exacerbates the anemia. The presence of fatigue associated with anemia has a substantially negative impact on quality of life and the ability to perform activities of daily living. Options for alleviating perioperative anemia include minimizing surgical blood loss, blood transfusion, supplementation with hematinics, such as iron and folic acid, and treatment with recombinant human erythropoietin. Treating preoperative anemia is expected to help correct anemia prior to surgery and may have a positive impact on anemia-related symptoms and surgical outcomes.

Topics: Anemia; Blood Loss, Surgical; Blood Transfusion; Elective Surgical Procedures; Epoetin Alfa; Erythropoietin; Fatigue; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Hematinics; Hematocrit; Humans; Hysterectomy; Preoperative Care; Recombinant Proteins

Erythropoietin, a glycoprotein hormone, is synthesized predominantly in the kidney and secreted by renal cortical interstitial cells in response to tissue hypoxia. Erythropoietin is the main regulator of the production of red blood cells. It functions in the recruitment and differentiation of erythroid progenitor cells and aids in their maintenance and survival. Erythropoietin also stimulates the synthesis of hemoglobin. In the last 15 years, the ready availability of recombinant human erythropoietin (r-HuEPO, epoetin alfa) has permitted the clinical investigation and application of this hormone to the treatment of anemia in various patient populations. Epoetin alfa has been shown to accelerate erythropoiesis and reduce allogeneic blood transfusion in major elective, noncardiac, nonvascular surgery and in certain anemic patients with chronic renal failure, nonmyeloid malignancies and human immunodeficiency virus infection. In addition to improving hematologic parameters, epoetin alfa therapy can enhance health-related quality of life in these patients. The success of epoetin alfa in treating anemia in other surgical populations suggests that it may be of benefit in treating the perioperative anemia that is highly prevalent in gynecologic surgery patients. Further investigation of the use of epoetin alfa in patients undergoing gynecologic surgery would increase awareness of its benefits for this patient population.

Topics: Anemia; Elective Surgical Procedures; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Gynecologic Surgical Procedures; Hematinics; Humans; Perioperative Care; Quality of Life; Recombinant Proteins

Recombinant human erythropoietin (r-HuEPO, epoetin alfa) is used for treatment of anemia associated with chemotherapy for non-myeloid malignancies, chronic renal failure and zidovudine treatment in patients infected with the human immunodeficiency virus and for anemic patients undergoing elective, noncardiac, nonvascular surgery. Epoetin alfa has been shown to safely increase preoperative hemoglobin (Hb) levels in anemic patients undergoing elective noncardiac, nonvascular surgery and is more effective than preoperative autologous blood donation in reducing the need for perioperative blood transfusions in orthopedic surgery patients. Epoetin alfa was shown to significantly increase Hb levels and decrease transfusion requirements in gynecologic cancer patients undergoing chemotherapy. A once-weekly regimen of 40,000 IU per dose was effective in these patients. In addition to decreasing transfusion requirements and increasing Hb, epoetin alfa for relieving anemia-related fatigue and improving quality of life was demonstrated in clinical trials in anemic cancer patients receiving chemotherapy. With regard to quality of life in orthopedic surgery patients, a novel instrument to measure the effect of Hb management on postoperative recuperative power (i.e., vigor, functional ability) has been validated and may prove to be useful in optimizing rehabilitation and discharge planning. Extensive clinical experience with epoetin alfa in anemic patients undergoing major elective orthopedic surgery or those with gynecologic cancer provides a strong basis for its use in gynecologic surgery.

Topics: Anemia; Blood Transfusion; Elective Surgical Procedures; Epoetin Alfa; Erythropoietin; Fatigue; Female; Gynecologic Surgical Procedures; Hematinics; Hemoglobins; Humans; Neoplasms; Orthopedics; Quality of Life; Recombinant Proteins; Safety; Treatment Outcome

Perioperative anemia is a common complication of major surgery that may lead to prolonged and debilitating fatigue and reduction in health-related quality of life (QOL). Treatment with recombinant human erythropoietin (r-HuEPO, epoetin alfa) has been shown to increase perioperative hemoglobin (Hb) and hematocrit (HCT) levels, thereby facilitating postoperative recovery in orthopedic surgery patients. Treatment with epoetin alfa has also been shown to increase Hb and HCT levels and improve QOL in anemic cancer patients undergoing chemotherapy. The clinical and QOL benefit of using epoetin alfa in these patient populations provides the rationale for its use in patients undergoing gynecologic surgery. Because persistent fatigue is the most common complaint of patients following hysterectomy, the use of epoetin alfa should be considered to preoperatively correct anemia in this patient population. Research has been initiated to increase our understanding of the role of epoetin alfa in treating anemic patients (Hb levels < or = 13 g/dL) undergoing surgery for benign gynecologic disease, especially as it relates to postoperative QOL. Future studies should investigate the use of epoetin alfa in patients with gynecologic cancers. These studies should confirm the role of epoetin alfa in combination with iron supplementation to improve perioperative Hb/HCT levels and overall QOL in patients undergoing gynecologic surgery.

Topics: Anemia; Elective Surgical Procedures; Epoetin Alfa; Erythropoietin; Fatigue; Female; Forecasting; Gynecologic Surgical Procedures; Hematinics; Humans; Perioperative Care; Quality of Life; Recombinant Proteins; Safety; Treatment Outcome

Anemia is a common cause of cancer-related fatigue. A systematic review of the literature was performed to establish guidelines on the use of epoetin alfa for the treatment of anemia. The evidence in support of these guidelines was selected, reviewed, and summarized by the members of the Canadian Cancer and Anemia Guidelines Development Group. The effects of epoetin alfa on quality of life (QOL) in patients with cancer were examined in 5 randomized, placebo-controlled trials and 2 large, open-label, nonrandomized, community-based studies. The effects of epoetin alfa on red blood cell transfusion requirements were examined in 19 randomized controlled trials (RCTs) with 21 comparisons. All trials compared epoetin alfa to a suitable control group, examined specified outcome measures that could be analyzed, and studied patients with cancer who were receiving chemotherapy. Trials involving patients with hematologic malignancies originating in the bone marrow were excluded. Outcome measures included 1) quality of life (QOL) (as measured by scales including the Linear Analogue Self-Assessment [LASA] and the Functional Assessment of Cancer Therapy [FACT] subscales), and 2) transfusion requirements (as measured by the proportion of patients requiring transfusion and amount of transfusion). The analysis confirmed that epoetin alfa produced statistically significant and clinically relevant improvements in QOL in patients with cancer. The overall relative risk ratio for transfusion among patients receiving epoetin alfa was calculated to be 0.60 (95% Cl, 0.53-0.69; P < 0.00001), representing a 40% reduction in the proportion of patients requiring transfusion. These results support recommendations for the use of epoetin alfa in patients with cancer-related anemia.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins

Topics: Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Subcutaneous; Recombinant Proteins

Topics: Adult; Anemia; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins

Anemia is frequent and significantly adds to the morbidity of cancer patients, and has been associated with decreased quality of life (QOL). Three open-label community-based studies of epoetin alfa in cancer-related anemia (two using three-times-weekly dosing and one using once-weekly dosing) in more than 7,000 patients have been performed. Results indicate that epoetin alfa treatment significantly increases hemoglobin and reduces transfusion requirements by 8 to 12 weeks, and using quality assessment tools, it has been shown to be associated with improvement in QOL scores. Incremental analysis demonstrated that the greatest improvement in QOL outcomes was associated with an increase in hemoglobin level from 11 g/dL to 12 g/dL (range, 11 to 13 g/dL). Strategies for management of anemia may need to take into account the possible advantage of early intervention in improving functional status in cancer patients.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Epoetin (Epo) is physiologically present in the human body, stimulating erythropoiesis from bone marrow. Anemia is observed in cancer patients submitted to high-dose chemotherapy (HDCT), mainly caused by myelosuppression. Epoetin alfa has been widely used to treat the anemia that develops in the HDCT setting. Controlled studies in patients with hematologic malignancies or solid tumors who received Epo following HDCT have shown a decreased red blood cell transfusion requirement at least in patients receiving allogeneic bone marrow transplantation (BMT), while results in patients receiving autologous BMT have been disappointing. The administration of Epo before HDCT, in a period when bone marrow is still responsive to growth factors, may represent a new strategy aimed at decreasing the degree of anemia in these patients. A combination of granulocyte-colony stimulating factor and Epo has proved to be effective in mobilizing stem cell and committed myeloid/erythroid precursors.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Bone Marrow; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Hemoglobin A; Humans; Recombinant Proteins

A wide variety of prescribed and over-the-counter (OTC) agents can affect the production or viability of red blood cells, thereby contributing to anemia. An apparent hyporesponse to Epoetin alfa therapy in end-stage renal disease (ESRD) patients can sometimes be traced to a medication prescribed to treat a comorbid condition. The anemic potential of many of these agents has been defined and can often be anticipated or avoided by examining and modifying the regimen. Nurses can help assess and prevent medicine-related hyporesponse to Epoetin alfa by obtaining thorough histories and providing ongoing counseling on the need to minimize exposure to substances that contribute to anemia. A case study is provided to illustrate the use of nursing assessment skills to identify potential drug-related hyporesponse to Epoetin alfa.

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Education, Nursing, Continuing; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Recombinant human erythropoietin (Epoetin alfa) is effective in increasing hemoglobin concentration and hematocrit, and in significantly reducing transfusion requirements in the majority of patients with either the anemia of chronic renal failure or chemotherapy-induced anemia of cancer. Identification of factors that could enable the clinician to predict individual patient hematological responses to Epoetin alfa therapy would be of great value. Changes in levels of serum transferrin receptor protein, hemoglobin, ferritin and reticulocyte count, following a short course of Epoetin alfa therapy, were useful markers for predicting later hematopoietic responses to Epoetin alfa. In addition, recent data suggest that low baseline erythropoietin levels, in association with increases of either >0.5 g/dl in hemoglobin or >/=25% in circulating levels of transferrin receptor protein after 2 weeks of Epoetin alfa therapy, are highly predictive of a response (>/=2 g/dl increase in hemoglobin) to Epoetin alfa. Progress has clearly been made in the development of predictive models that can identify those patients most likely to respond to Epoetin alfa by monitoring several specific hematological parameters at baseline and early in therapy. Future studies will focus on nonhematological measures of response, such as transfusion requirement and quality of life benefit.

Topics: Anemia; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Hematopoiesis; Humans; Neoplasms; Predictive Value of Tests; Recombinant Proteins; Treatment Outcome

Anemia is a common complication of myelosuppressive chemotherapy that results in a decreased functional capacity and quality of life (QOL) for cancer patients. Severe anemia is treated with red blood cell transfusions, but mild-to-moderate anemia in patients receiving chemotherapy has traditionally been managed conservatively on the basis of the perception that it was clinically unimportant. This practice has been reflected in the relative inattention to standardized and complete reporting of all degrees of chemotherapy-induced anemia. We undertook a comprehensive review of published chemotherapy trials of the most common single agents and combination chemotherapy regimens, including the new generation of chemotherapeutic agents, used in the treatment of the major nonmyeloid malignancies in adults to characterize and to document the incidence and severity of chemotherapy-induced anemia. Despite identified limitations in the grading and reporting of treatment-related anemia, the results confirm a relatively high incidence of mild-to-moderate anemia. Recent advances in assessing the relationships of anemia, fatigue, and QOL in cancer patients are providing new insights into these closely related factors. Clinical data are emerging that suggest that mild-to-moderate chemotherapy-induced anemia results in a perceptible reduction in a patient's energy level and QOL. Future research may lead to new classifications of chemotherapy-induced anemia that can guide therapeutic interventions on the basis of outcomes and hemoglobin levels. Perceptions by oncologists and patients that lesser degrees of anemia must be endured without treatment may be overcome as greater emphasis is placed on the QOL of the oncology patient and as research provides further insights into the relationships between hemoglobin levels, patient well-being, and symptoms.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Colorectal Neoplasms; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Head and Neck Neoplasms; Hematinics; Humans; Incidence; Lung Neoplasms; Lymphoma; Middle Aged; Neoplasms; Ovarian Neoplasms; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

The amount of transfused blood is related to blood loss calculated for the specific type of surgical procedure, transfusion hematocrit trigger and patient's red blood cell mass on the day before surgery. To optimise the benefit/cost and benefit/risk ratios of blood transfusion, a correct prescription must be done in accordance with the patient's red blood cell mass and surgical blood loss. Indeed, there is a clear need to define the appropriate uses of blood management methods and to seek new methods of improving perioperative blood management. The number of moderately anaemic patients undergoing surgery is currently thought to be 20%. Where transfusion requirements are estimated at two to three blood units, as for instance in the most common types of orthopaedic surgery, preoperative haemoglobin is the key factor governing transfusion needs. In this case, the simplest approach is to prescribe Epoetin Alfa subcutaneous at a dose of 600 IU/kg/week starting three weeks before the surgery. In addition, it is important in all cases to give concomitant iron supplements. Concomitant use of other methods to decrease allogeneic blood requirements is of no value. Obviously, the higher the haematocrit the day prior to surgery, the higher the patient's RBC mass and the greater the patient's permitted blood loss, decreasing the transfusion trigger. In this way, allogeneic blood loss is reduced, but without the need for the patient to attend the blood transfusion center and to undergo laboratory screening and testing of donated blood, and without the risk of inducing preoperative anaemia compared with sequential autologous blood donation. But, to optimise the benefit/cost ratio, we try to define precisely the patient populations likely to benefit from preoperative erythropoietin. Using different examples, management is proposed with algorithms.

Topics: Anemia; Blood Loss, Surgical; Blood Transfusion; Blood Transfusion, Autologous; Comorbidity; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Evaluation Studies as Topic; Hematocrit; Humans; Infusions, Intravenous; Intraoperative Care; Iron; Multicenter Studies as Topic; Orthopedics; Premedication; Preoperative Care; Recombinant Proteins

Epoetin alfa is the cornerstone of anemia therapy in patients with end-stage renal disease. In addition to stimulating erythropoiesis, Epoetin alfa has been demonstrated to affect hemostasis. Such effects may be important because patients with chronic renal failure have a bleeding diathesis that is multifactorial in origin. Therefore, a computer literature search on the relationship between Epoetin alfa therapy for anemia in patients with end-stage renal disease and platelets, coagulation, coagulation inhibitors, and fibrinolysis was performed. All articles and abstracts reporting original data in the English language on Epoetin alfa and its effect on hemostasis were reviewed. The literature suggests that the effects of Epoetin alfa on the coagulation cascade are of minimal clinical importance. However, Epoetin alfa transiently increases the number of circulating platelets and improves platelet function, and these effects are associated with a return of the bleeding time towards normal.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Fibrinolysis; Hematinics; Hemostasis; Humans; Kidney Failure, Chronic; Recombinant Proteins

Recombinant human erythropoietin (EPO; epoetin) has been shown to be effective in improving anemia in a proportion of cancer patients. The response rate is approximately 60%, but varies considerably according to baseline hematocrit and transfusion needs, as well as the response criteria used. Response is not greatly influenced by the type of tumor, except in situations of major marrow involvement and limited residual hematopoiesis, or in the presence of specific mechanisms of anemia, such as hemolysis, splenomegaly, bleeding, hemodilution, or ineffective erythropoiesis. Stem cell damage by previous therapy as well as marrow suppression by current intensive chemotherapy can impair response. Besides its intensity, the type of chemotherapy may not be critical, although patients undergoing platinum-based chemotherapy may respond faster than those receiving non-platinum regimens. Complications, such as infections, bleeding, or nutritional deficiencies, may have a major negative impact on outcome. An important response-limiting factor is functional iron deficiency (ie, an imbalance between iron needs in the erythropoietic marrow and iron supply), which depends on the level of iron stores and its rate of mobilization. Functional iron deficiency is best monitored by the percentage of hypochromic red blood cells, and oral or intravenous iron supplements should be given when this percentage increases above 10%. All these factors explain why the response rate to epoetin is only approximately 60%. Therefore, it would be interesting to develop models that could help predict response to epoetin to help select the most appropriate cancer patients for this therapy. Few baseline parameters have been shown to be highly predictive of response in patients with solid tumors, although most studies in patients with myeloma or lymphoma have indicated that patients with a low baseline serum EPO level will respond better. Early changes after 2 to 4 weeks of treatment are also of great interest. Among these early changes, increments of soluble transferrin receptor, reticulocytes, and hemoglobin, as well as the persistence of elevated ferritin or EPO levels, have all shown some predictive value. Combination of baseline serum EPO and the 2-week increment of soluble transferrin receptor or hemoglobin may provide the best prediction of response.

Topics: Algorithms; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Models, Biological; Neoplasms; Recombinant Proteins

Patients with cancer have inappropriately low levels of endogenous erythropoietin for the degree of anemia and further suppression of erythropoiesis results from chemotherapy. Patients with lung cancer, in particular, require a high frequency of transfusions, as they are unable to tolerate the symptoms of anemia due to their underlying pulmonary disease and, often, their age. Data from phase I and II trials indicated that epoetin alfa could increase hemoglobin concentration and reduce transfusion requirements. The beneficial response was dose dependent. These findings were confirmed in a series of three double-blind, placebo-controlled, multicenter phase III trials. Clinical trial evidence indicates that 150 IU/kg epoetin alfa three times weekly effectively treats anemia and decreases transfusion requirements in most cancer patients after the first month of chemotherapy. Furthermore, epoetin alfa will reduce the degree of anemia and markedly reduce the need for transfusions, thereby preventing anemia in patients undergoing multiple cycles of platinum-based combination chemotherapy. Epoetin alfa is well tolerated and shows marked activity in preventing anemia and reducing blood transfusion requirements in patients undergoing cyclic chemotherapy.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Anemia is common in patients infected with the human immunodeficiency virus (HIV). The etiology is often multifactorial and may include the HIV infection itself, opportunistic infections, cancer, medications (particularly zidovudine and sulfa-containing drugs), or anemia of chronic disease. Epoetin alfa therapy may play a supportive role in some HIV-infected patients by increasing hemoglobin, decreasing fatigue, and reducing the need for exposure to red blood cell transfusions. A large, placebo-controlled trial in the United States for anemic patients with the acquired immunodeficiency syndrome taking zidovudine demonstrated a statistically significant improvement in hematocrit in patients treated with epoetin alfa compared with placebo. Transfusion requirements decreased in epoetin alfa-treated patients over a 3-month period compared with placebo with a trend toward improvement in quality of life. Epoetin alfa was effective, however, only in patients whose pretreatment erythropoietin levels were less than 500 mU/mL. These advantages of epoetin alfa treatment may become especially important as HIV becomes more of a chronic disease, with the concern that red blood cell transfusion may accelerate progression of HIV.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Blood Transfusion; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins

First used successfully to correct the anemia associated with chronic renal failure, epoetin alfa has been shown to be highly effective in many patients with either hematologic or nonhematologic malignancies. Multiple studies have demonstrated effective response rates, with increases in hemoglobin concentration and reduction or elimination of transfusion requirements in up to 75% or 80% in such patients. Nevertheless, as clinical experience has grown, several issues have arisen. First, not all cancer patients respond to epoetin alfa and, consequently, it is important to identify those patients most likely to respond to make early clinical decisions regarding dose adjustment or drug withdrawal. Second, experience in patients with renal failure has revealed a state of "functional iron deficiency" and, thus, highlighted the importance of iron supplementation to optimize the response to epoetin alfa. Does "functional iron deficiency" complicate epoetin alfa therapy of patients with the anemia of cancer, and could such patients benefit from iron supplementation? Finally, some hematologic malignancies, especially myelodysplastic syndromes, can be resistant to epoetin alfa monotherapy. Can the effective response rates in such patients be improved by combining epoetin alfa therapy with the administration of other hematopoietic growth factors? Epoetin alfa has made substantial contributions to the care of patients with cancer and, with time, additional uses for this very valuable drug will become apparent.

Topics: Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Iron; Neoplasms; Quality of Life; Recombinant Proteins

Anemia associated with cancer and cytotoxic chemotherapy contributes adversely to the quality of life (QOL) of these patients. RBC transfusions have been the traditional treatment, but due to the associated risks, they are not routinely used to treat mild and moderate degrees of anemia Therapy with recombinant human erythropoietin ([EPO] epoetin alfa) in these patients has been effective for both prevention and treatment of anemia, and in decreasing transfusion requirements. More importantly, studies have shown that the addition of epoetin alfa therapy to the treatment of patients receiving cancer chemotherapy is associated with a significant increase in energy level, functional status, and overall QOL. Further studies will be required to define the most efficient and cost-effective dose and schedule of epoetin alfa during cancer chemotherapy, so that its benefits will be available to as many patients as possible. The most important studies will be focused on defining the relationship of dose to response, identifying early predictors of response, and determining cost-effectiveness.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Quality of Life; Recombinant Proteins

Under normal physiologic conditions the level of circulating red blood cells is regulated precisely by the glycoprotein erythropoietin. In major elective surgery, patients who are participating in preoperative autologous blood donation or who are anemic may not have the capacity to manufacture sufficient red blood cells in response to increases in endogenous erythropoietin that is sufficient to avoid perioperative allogeneic blood transfusion. In these patients pharmacologic doses of recombinant human erythropoietin (Epoetin alfa) have been shown to accelerate erythropoiesis, thereby increasing preoperative red blood cell production, hematocrit level, and hemoglobin concentration and reducing exposure to allogeneic blood transfusion. In four large multicenter studies, 869 patients undergoing major elective surgery were treated with a daily regimen (300 or 100 IU/kg x 14 or 15 doses) or a weekly regimen (600 IU/kg x 4 doses) of subcutaneous Epoetin alfa beginning either 2 or 3 weeks before surgery, respectively. Although all Epoetin alfa regimens were effective at accelerating erythropoiesis and increasing red blood cell production, the weekly regimen was the most patient friendly, cost effective regimen for treating preoperative anemia and minimizing patient risk of allogeneic blood transfusion.

Topics: Anemia; Blood Transfusion; Elective Surgical Procedures; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Humans; Intraoperative Complications; Multicenter Studies as Topic; Postoperative Complications; Recombinant Proteins; Safety

Improving patient outcomes by achieving a stable Hct in the higher end of the target Hct range of 30% to 36% is the primary goal of anemia management and Epoetin alfa therapy. Recently, attention has been focused on the potential differences between subcutaneous (s.c.) and intravenous (i.v.) administration. Although some patients may require less Epoetin alfa when it is administered by the s.c. route, many patients require the same dose or more due to the significant heterogeneity in response. To ensure that therapeutic outcomes are maintained or improved, clinicians should evaluate both staff considerations and individual patient tolerance and response when determining the optimal route of administration.

Topics: Anemia; Education, Nursing, Continuing; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins

High-dose chemotherapy is increasingly accepted as a treatment approach in a number of tumour types. However, there are controversies surrounding its efficacy and there is a need to consider its safety. In view of this, much effort has been directed towards the provision of adequate supportive care strategies to prevent toxicities and to ameliorate myelosuppression. Severe anaemia and its associated symptoms, for example, fatigue can have a debilitating effect on a patient's quality of life and often necessitates red blood cell transfusions. Erythropoietin, a glycoprotein hormone which stimulates red blood cell production, has been established for the treatment of anaemia in patients with chronic renal insufficiency. It is currently approved in most countries for treating anaemia associated with cancer, and its role is emerging especially in patients undergoing high-dose chemotherapy. This paper gives an overview of the studies conducted to date with epoetin alfa (recombinant human erythropoietin) in patients receiving allogeneic and autologous bone marrow transplants or peripheral blood stem cells in conjunction with high-dose chemotherapy. In addition, there are some novel clinical applications for epoetin alfa: for example, in delayed anaemia, as a supportive strategy prior to high-dose chemotherapy and as a synergistic enhancer of blood progenitor cell mobilisation in combination with granulocyte-colony-stimulating factor (G-CSF).

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cell Mobilization; Humans; Recombinant Proteins

Clinical evidence indicates that maintaining a stable hematocrit (Hct) higher in the target range of 30% to 36% can lead to improvement in overall patient outcomes. On the basis of these data, a recent analysis by the Dialysis Outcomes Quality Initiative Anemia Work Group has recommended a target Hct of 33% to 36% (hemoglobin 11 g/dl to 12 g/dl). Maintaining a stable Hct higher in the target range provides nurses and other dialysis clinicians with two benefits: improved patient care and decreased time and costs for patient management. This article focuses on the data supporting such a policy. Clinical practices from two prominent dialysis centers are presented as models of good anemia management.

Topics: Anemia; Body Weight; Epoetin Alfa; Erythropoietin; Health Status; Hematinics; Hematocrit; Humans; Kidney Failure, Chronic; Patient Care Planning; Recombinant Proteins; Survival Analysis

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Patient Selection; Predictive Value of Tests; Recombinant Proteins; Treatment Outcome

The ability of epoetin alfa to increase hematopoiesis in a dose-dependent manner when administered by the intravenous (i.v.) or subcutaneous (s.c.) route has been demonstrated in pharmacokinetic studies in healthy volunteers. Epoetin alfa may therefore be a useful adjunct to autologous blood (AB) donation. By facilitating AB donation, the use of allogeneic blood could be reduced. In patients scheduled to undergo orthopedic surgery, i.v. administration of epoetin alfa 600 IU/kg twice weekly for 3 weeks prior to surgery (in conjunction with oral iron supplementation) significantly increased the number of AB units and total red blood cell (RBC) volume donated and increased the number of patients able to donate > or = 4 AB units. However, there was no difference between epoetin alfa and placebo groups with respect to allogeneic blood exposure.

Topics: Anemia; Blood Transfusion, Autologous; Epoetin Alfa; Erythropoiesis; Erythropoietin; Ferrous Compounds; Hematocrit; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Orthopedics; Premedication; Recombinant Proteins

In patients scheduled for major orthopedic surgery, the presence of anemia can preclude the donation of sufficient autologous blood (AB) to meet transfusion requirements. Although a number of studies have investigated the use of epoetin alfa (in conjunction with parenteral iron supplementation) to facilitate AB donation and reduce exposure to allogeneic blood in this patient population, the optimum treatment regimen and route of administration has yet to be defined. In rheumatoid arthritis (RA) patients with a low predonation hematocrit (Hct; < or = 39%), intravenous (i.v.) treatment with epoetin alfa 300 IU/kg twice weekly for 3 weeks was the optimum dosage for facilitation of AB donation and minimization of the decrease in Hct prior to elective orthopedic surgery. However, the subcutaneous (s.c.) route of epoetin alfa administration may allow lower dosages of epoetin alfa to be used. Indeed, epoetin alfa 100 IU/kg s.c. twice weekly for 3 weeks (in conjunction with a single i.v. bolus of 200 IU/ kg at the first s.c. dose) was as effective as 300 IU/kg i.v. administered according to the same schedule. The number of AB units collected, total red blood cell (RBC) volume donated, and peak proportion of reticulocytes were similar regardless of the route of administration. Both treatment groups were associated with a significant reduction in allogeneic blood exposure compared with historical controls. Findings consistent to all of these studies were that epoetin alfa was well tolerated, and that i.v. iron supplementation was necessary to maximize its beneficial effects.

Topics: Anemia; Arthritis, Rheumatoid; Blood Transfusion; Blood Transfusion, Autologous; Dose-Response Relationship, Drug; Double-Blind Method; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematocrit; Humans; Injections, Intravenous; Injections, Subcutaneous; Orthopedics; Premedication; Recombinant Proteins; Treatment Outcome

The development of anemia is one factor that can limit the donation of sufficient autologous blood (AB) to meet a patient's expected blood requirements following elective orthopedic surgery. Two clinical studies have been conducted in nonanemic patients to investigate the use of epoetin alfa as an adjuvant to AB predonation to facilitate AB procurement and minimize the development of anemia. Both studies demonstrated that patients with a normal hematocrit (Hct) can donate > or = 3 units of AB prior to surgery. However, treatment with epoetin alfa minimized the decrease in Hct associated with AB donation. While there was a trend toward a reduction in allogeneic blood exposure in patients treated with epoetin alfa, the difference relative to placebo was not significant. This observation may be explained by a limited requirement for blood in this patient population that was met by predonation of 3 AB units. Thus, the use of epoetin alfa as an adjunct to AB predonation is likely to be of most benefit in patients with a normal Hct scheduled for surgical procedures where the expected blood requirements exceed 3 units. In addition, epoetin alfa may enable patients with a low Hct, low body weight, or low predicted blood volume to participate in or to complete an AB donation program, thus reducing the possibility of exposure to allogeneic blood.

Topics: Anemia; Blood Transfusion; Blood Transfusion, Autologous; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematocrit; Hemoglobins; Humans; Iron; Orthopedics; Premedication; Recombinant Proteins; Treatment Outcome

Patients undergoing cancer surgery frequently require blood, and the transfusion of allogeneic blood in these patients has been controversially linked to an increased risk of tumor recurrence. This patient population may therefore benefit from preoperative autologous blood donation (ABD) with or without epoetin alfa therapy, although the precise impact of autologous blood transfusion has not been fully explored. In some trials, preoperative ABD reduced allogeneic blood exposure by 50% in patients undergoing surgery for cancer resection, while, in another study, perioperative treatment with epoetin alfa significantly increased hematocrit (Hct) levels preoperatively and led to a reduction in postoperative allogeneic blood exposure. A combination of epoetin alfa and preoperative ABD seems a reasonable approach to reducing allogeneic blood exposure in patients undergoing cancer surgery.

Topics: Anemia; Blood Transfusion; Blood Transfusion, Autologous; Colorectal Neoplasms; Disease-Free Survival; Epoetin Alfa; Erythropoiesis; Erythropoietin; Gastrointestinal Neoplasms; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Premedication; Prospective Studies; Recombinant Proteins; Survival Rate; Transfusion Reaction; Treatment Outcome

The introduction of autologous blood (AB) donation programs has led to a decrease in the number of orthopedic surgery patients exposed to allogeneic blood, although there is still room for improvement. For example, some patients may not be able to donate sufficient AB to meet their expected blood requirements. Virtually all nonanemic patients can donate 3 AB units prior to orthopedic surgery before further AB donation is limited by the development of anemia. In preliminary studies, the administration of epoetin alfa (150 IU/kg subcutaneously (s.c.) on alternate days; six doses) following the donation of 3 AB units reversed phlebotomy-induced anemia and enabled a further 2 units of AB to be collected. The ability of this therapeutic approach to increase AB procurement and reduce allogeneic blood requirements is being investigated in an ongoing, placebo-controlled study. An alternative approach may be to combine perisurgical treatment with epoetin alfa and normovolemic hemodilution (NVHD) prior to orthopedic surgery. Although such studies have yet to be initiated, they may demonstrate a reduction in allogeneic blood exposure in patients unable to donate AB prior to orthopedic surgery, a group of patients traditionally at high risk of exposure to allogeneic blood.

Topics: Anemia; Blood Loss, Surgical; Blood Transfusion, Autologous; Blood Volume; Clinical Trials as Topic; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hemodilution; Humans; Orthopedics; Premedication; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Kidney Diseases

Topics: Anemia; Anemia, Macrocytic; Blood Platelets; Eosinophilia; Epoetin Alfa; Erythropoietin; Humans; Iron; Leukemia; Polycythemia Vera; Vitamin B 12

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematopoiesis; Humans; Kidney; Kidney Diseases; Kidney Neoplasms; Pathology; Physiology; Polycythemia

The optimum starting dose of intravenous continuous erythropoietin receptor activator (C.E.R.A.) has been previously determined; this study ascertains the optimum starting dose of subcutaneous C.E.R.A. administration in pediatric patients.. Phase 2, open-label, single-arm, multicenter study.. Patients aged 3 months to 17 years with renal anemia and chronic kidney disease (CKD; including those treated with maintenance dialysis and those not treated with dialysis) who were receiving maintenance treatment with erythropoiesis-stimulating agents (ESAs).. Subcutaneous C.E.R.A. administration every 4 weeks (starting dose was based on defined conversion factors).. The primary outcome was the change in hemoglobin concentration between the baseline and evaluation period for each patient. Secondary efficacy measures and safety were also evaluated.. Forty patients aged 0.4-17.7 years were enrolled. The study achieved its primary outcome: the mean change in hemoglobin concentration was an increase of 0.48g/dL; the 95% confidence interval (0.15-0.82) and standard deviation (±1.03) were within the prespecified boundaries (-1 to 1g/dL and<1.5g/dL, respectively). Mean hemoglobin concentrations were maintained within the target 10-12g/dL range in 24 of 38 patients and within±1g/dL of the baseline in 19 of 38 patients, and the median C.E.R.A. subcutaneous dose decreased over time. Efficacy in key subgroups (age group, dialysis type, prior ESA treatment) was consistent with the primary outcome. Thirty-eight patients completed the core period; 25 chose to enter the safety extension period. Safety was consistent with prior studies, with no new signals.. Single-arm and open-label study; small sample size.. Pediatric patients with anemia secondary to CKD who were on, or not on, dialysis could be safely and effectively switched from maintenance ESAs to subcutaneous C.E.R.A. administered every 4 weeks, using defined dose-conversion factors to determine the optimum starting dose.. F. Hoffmann-La Roche Ltd.. The SKIPPER trial registered at ClinicalTrials.gov with study number NCT03552393.. Anemia, a complication of chronic kidney disease, is associated with poor quality of life and an increased risk of hospitalization and mortality. The current treatments for anemia include iron therapy and erythropoiesis-stimulating agents (ESAs); however, the relatively short half-lives of the ESAs epoetin alfa/beta or darbepoetin alfa may require more frequent dosing and hospital visits compared with the ESA known as continuous erythropoietin receptor activator (C.E.R.A.). A previous study demonstrated that children aged 5 years or more with anemia associated with chronic kidney disease who were on hemodialysis could be switched to intravenous C.E.R.A. from their existing epoetin alfa/beta or darbepoetin alfa treatment. This study provides evidence that subcutaneous C.E.R.A. can safely and effectively treat anemia in children, including those aged<5 years and regardless of whether they were on dialysis or the type of dialysis they received (peritoneal dialysis or hemodialysis).

Topics: Anemia; Child; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Quality of Life; Renal Dialysis; Renal Insufficiency, Chronic

Erythropoiesis-stimulating agents (ESAs) are the standard-of-care treatment for anaemia in most patients with lower-risk myelodysplastic syndromes but responses are limited and transient. Luspatercept promotes late-stage erythroid maturation and has shown durable clinical efficacy in patients with lower-risk myelodysplastic syndromes. In this study, we report the results of a prespecified interim analysis of luspatercept versus epoetin alfa for the treatment of anaemia due to lower-risk myelodysplastic syndromes in the phase 3 COMMANDS trial.. The phase 3, open-label, randomised controlled COMMANDS trial is being conducted at 142 sites in 26 countries. Eligible patients were aged 18 years or older, had a diagnosis of myelodysplastic syndromes of very low risk, low risk, or intermediate risk (per the Revised International Prognostic Scoring System), were ESA-naive, and required red blood cell transfusions (2-6 packed red blood cell units per 8 weeks for ≥8 weeks immediately before randomisation). Integrated response technology was used to randomly assign patients (1:1, block size 4) to luspatercept or epoetin alfa, stratified by baseline red blood cell transfusion burden (<4 units per 8 weeks vs ≥4 units per 8 weeks), endogenous serum erythropoietin concentration (≤200 U/L vs >200 to <500 U/L), and ring sideroblast status (positive vs negative). Luspatercept was administered subcutaneously once every 3 weeks starting at 1·0 mg/kg body weight with possible titration up to 1·75 mg/kg. Epoetin alfa was administered subcutaneously once a week starting at 450 IU/kg body weight with possible titration up to 1050 IU/kg (maximum permitted total dose of 80 000 IU). The primary endpoint was red blood cell transfusion independence for at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1-24), assessed in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. The COMMANDS trial was registered with ClinicalTrials.gov, NCT03682536 (active, not recruiting).. Between Jan 2, 2019 and Aug 31, 2022, 356 patients were randomly assigned to receive luspatercept (178 patients) or epoetin alfa (178 patients), comprising 198 (56%) men and 158 (44%) women (median age 74 years [IQR 69-80]). The interim efficacy analysis was done for 301 patients (147 in the luspatercept group and 154 in the epoetin alfa group) who completed 24 weeks of treatment or discontinued earlier. 86 (59%) of 147 patients in the luspatercept group and 48 (31%) of 154 patients in the epoetin alfa group reached the primary endpoint (common risk difference on response rate 26·6; 95% CI 15·8-37·4; p<0·0001). Median treatment exposure was longer for patients receiving luspatercept (42 weeks [IQR 20-73]) versus epoetin alfa (27 weeks [19-55]). The most frequently reported grade 3 or 4 treatment-emergent adverse events with luspatercept (≥3% patients) were hypertension, anaemia, dyspnoea, neutropenia, thrombocytopenia, pneumonia, COVID-19, myelodysplastic syndromes, and syncope; and with epoetin alfa were anaemia, pneumonia, neutropenia, hypertension, iron overload, COVID-19 pneumonia, and myelodysplastic syndromes. The most common suspected treatment-related adverse events in the luspatercept group (≥3% patients, with the most common event occurring in 5% patients) were fatigue, asthenia, nausea, dyspnoea, hypertension, and headache; and none (≥3% patients) in the epoetin alfa group. One death after diagnosis of acute myeloid leukaemia was considered to be related to luspatercept treatment (44 days on treatment).. In this interim analysis, luspatercept improved the rate at which red blood cell transfusion independence and increased haemoglobin were achieved compared with epoetin alfa in ESA-naive patients with lower-risk myelodysplastic syndromes. Long-term follow-up and additional data will be needed to confirm these results and further refine findings in other subgroups of patients with lower-risk myelodysplastic syndromes, including non-mutated SF3B1 or ring sideroblast-negative subgroups.. Celgene and Acceleron Pharma.

Topics: Aged; Anemia; Body Weight; COVID-19; Dyspnea; Epoetin Alfa; Erythropoiesis; Female; Hematinics; Hemoglobins; Humans; Hypertension; Male; Myelodysplastic Syndromes; Neutropenia

Anemia is one of the most common complications of Chronic Kidney Disease (CKD). The vast majority of Egyptian CKD patients are interchangeably treated with Darbepoetin Alfa (DPA) and Epoetin Alfa (EPA) to achieve and maintain target hemoglobin levels. Our study aimed to compare the efficacy and safety of DPA versus EPA for managing anemia amongst Egyptian patients with CKD undergoing dialysis.. A multicenter, open label, randomized, prospective, parallel study was conducted. Patients with CKD undergoing dialysis with Hb level < 10 g/dl were enrolled. The primary efficacy endpoint was the change in hemoglobin concentration at the evaluation period (weeks 20-24). Prespecified adverse events of interest following administration, including blood transfusions requirement, blood pressure and hemoglobin excursions, the relationship between C - Reactive Protein (CRP) and hemoglobin, were assessed.. Only 98 of 104 enrolled patients completed the study, fifty patients received EPA, and 48 patients received DPA. Our results showed that a significantly higher percentage of patients who achieved target Hb level ≥ 11 g/dL in DPA treated group vs. EPA as well as the meantime to achieve Hb level ≥ 10 g/dL was shorter in DPA treated group. Safety profiles of both treatments were similar. A negative correlation was observed between serum CRP and hemoglobin level in hemodialysis patients.. Our study showed that DPA was more effective and well tolerated in achieving and maintaining Hb levels with lower dosing frequency compared to EPA. Furthermore, CRP is recommended to be routinely measured where patients with higher CRP require high ESA doses.

Topics: Anemia; Darbepoetin alfa; Egypt; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Prospective Studies; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

The efficacy of recombinant human erythropoietin (rHuEPO) in sparing red blood cell (RBC) transfusions in children with hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) is uncertain.. We conducted a pilot randomized controlled open trial between December 2018 and January 2021. Children were randomized to the intervention (subcutaneous rHuEPO 50 U/kg three times weekly until discharge + RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability) or to the control arm (RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability). Primary outcome was the number of RBC transfusions received during hospitalization. Secondary outcomes were to explore whether baseline EPO levels were adequate to the degree of anemia, to correlate selected acute phase parameters with the number of RBC transfusions, and to assess possible adverse events.. Twelve patients per arm were included; they were comparable at recruitment and throughout the disease course. Median number of RBC transfusions was similar between groups (1.5, p = 0.76). Most patients had baseline EPO levels adequate to the degree of anemia, which did not correlate with the number of transfusions (r = 0.19, p = 0.44). Conversely, baseline (r = 0.73, p = 0.032) and maximum lactic dehydrogenase levels (r = 0.78, p = 0.003), creatinine peak (r = 0.71, p = 0.03) and dialysis duration (r = 0.7, p = 0.04) correlated significantly with RBC requirements. No side effects were recorded.. In children with STEC-HUS, the administration of rHuEPO did not reduce the number of RBC transfusions. Larger studies addressing higher doses and similar severity of kidney failure at rHuEPO initiation (e.g. at start of dialysis) are warranted.. ClinicalTrials.gov identifier: NCT03776851. A higher resolution version of the Graphical abstract is available as Supplementary information.

Topics: Anemia; Child; Epoetin Alfa; Erythropoietin; Hemoglobins; Hemolytic-Uremic Syndrome; Humans; Pilot Projects; Recombinant Proteins; Renal Dialysis

A phase 3 study to assess the efficacy and safety of the desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, against the epoetin alfa for the treatment of anemia in patients with chronic kidney disease (CKD) with dialysis dependency.. DREAM-D was a phase 3, multicenter, open-label, randomized, active-controlled clinical study conducted across 38 centers in India. A total of 392 patients with clinical diagnosis of anemia due to CKD with dialysis need (Erythrocyte Stimulating Agent [ESA] naïve or prior ESA users) and with baseline hemoglobin levels of 8.0-11.0 g/dL (inclusive) were randomized in a 1:1 ratio to receive either desidustat oral tablets (thrice a week) or epoetin alfa subcutaneous injection for 24 weeks to maintain a hemoglobin level of 10-12 g/dL. The primary endpoint was to assess the change in the hemoglobin level between the desidustat and the epoetin alfa groups from the baseline to evaluation period week 16-24. The key secondary efficacy endpoint was the number of patients with hemoglobin response.. The least square mean (standard error) change in hemoglobin from the baseline to week 16-24 was 0.95 (0.09) g/dL in the desidustat group and 0.80 (0.09) g/dL in the epoetin alfa group (difference: 0.14 [0.14] g/dL; 95% confidence interval: -0.1304, 0.4202), which met the prespecified noninferiority margin. The number of hemoglobin responders was significantly higher in the desidustat group (106 [59.22%]) when compared to the epoetin alfa group (89 [48.37%]) (p = 0.0382). The safety profile of the desidustat oral tablet was comparable with the epoetin alfa injection. There were no new risks or no increased risks seen with the use of desidustat compared to epoetin alfa.. In this study, desidustat was found to be noninferior to epoetin in the treatment of anemia in CKD patients on dialysis and it was well-tolerated. Clinical Trial Registry Identifier: CTRI/2019/12/022312 (India).

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Quinolones; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

Daprodustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) being investigated for the treatment of anemia of CKD. In this noninferiority trial, we compared daprodustat administered three times weekly with epoetin alfa (epoetin) in patients on prevalent hemodialysis switching from a prior erythropoiesis-stimulating agent (ESA).. Daprodustat three times weekly was noninferior to epoetin for mean change in hemoglobin (model-adjusted mean treatment difference [daprodustat-epoetin], -0.05; 95% confidence interval, -0.21 to 0.10). During the evaluation period, mean (SD) hemoglobin values were 10.45 (0.55) and 10.51 (0.85) g/dl for daprodustat and epoetin groups, respectively. Responders (defined as mean hemoglobin during the evaluation period in the analysis range of 10 to 11.5 g/dl) were 80% in the daprodustat group versus 64% in the epoetin group. Proportionately fewer participants in the daprodustat group versus the epoetin group had hemoglobin values either below 10 g/dl or above 11.5 g/dl during the evaluation period. Mean monthly intravenous iron use was not significantly lower with daprodustat versus epoetin. The effect on BP was similar between groups. The percentage of treatment-emergent adverse events was similar between daprodustat (75%) and epoetin (79%).. Daprodustat was noninferior to epoetin in hemoglobin response and was generally well tolerated.. Anemia Studies in Chronic Kidney Disease: Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor Daprodustat-Three Times Weekly Dosing in Dialysis (ASCEND-TD), NCT03400033.

Topics: Anemia; Double-Blind Method; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Iron; Prolyl-Hydroxylase Inhibitors; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome

EPREX®/ERYPO®/PROCRIT® (epoetin alfa, Janssen-Cilag GmbH) was the first available recombinant human erythropoietin (rHuEPO) and was universally reference product as per the recommendation provided by European Medicines Agency. EPIAO® is a biosimilar formulation of EPREX®, and making it a 1:1 dose conversion from EPREX® according to recommendation of European Medicines Agency. This study evaluated the clinical efficacy and safety of EPIAO® in subjects with end-stage renal disease receiving hemodialysis after intravenous administration.. This study was a multicenter, prospective, randomized, double-blind, parallel-group, 2-cohort, maintenance phase, therapeutic equivalence study to evaluate a 1:1 dose conversion from EPREX® to EPIAO® in terms of clinical efficacy and safety that was conducted at 20 sites in 2 countries in patients with end-stage renal disease on hemodialysis. Eligible subjects were treated with EPREX® (reference product of epoetin) for a period of at least 3 months before the treatment period, and then were randomly assigned to the group of EPREX® or EPIAO®. Primary endpoints were mean absolute change in hemoglobin level and mean absolute change in weekly epoetin dosage from baseline to 6 months after treatment with EPIAO®/EPREX® in parallel groups.. A total of 200 people received the random intervention and were included in the safety set. After 6, 9, and 12 months of treatment with EPIAO® or EPREX®, there were no significant differences in the hemoglobin levels of the 2 groups compared with baseline. The 95% confidence interval for the treatment difference was within the predetermined acceptable range: ±0.5 g/dL. There were no significant differences in the epoetin dosage of the 2 groups compared with the baseline. The 95% confidence interval for the treatment difference was within the predetermined acceptable range: ± 45 IU/kg. There were no significant differences in the incidence of adverse events between the EPIAO® and EPREX® groups. Most adverse events were mild to moderate and were reverted/resolved.. EPIAO® demonstrated promising effectiveness and manageable safety in patients with end-stage renal disease on hemodialysis.

Topics: Anemia; Biosimilar Pharmaceuticals; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Prospective Studies; Renal Dialysis; Translocation, Genetic; Treatment Outcome

The Anemia Studies in chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Dialysis (ASCEND-D) trial will test the hypothesis that daprodustat is noninferior to comparator epoetin alfa or darbepoetin alfa for two co-primary endpoints: hemoglobin (Hb) efficacy and cardiovascular (CV) safety.. We report the trial design, key demographic, clinical and laboratory findings, and baseline therapies of 2964 patients randomized in the open-label (sponsor-blinded) active-controlled, parallel-group, randomized ASCEND-D clinical trial. We also compare baseline characteristics of ASCEND-D patients with patients who are on dialysis (CKD G5D) enrolled in other large CV outcome trials (CVOTs) and in the most relevant registries.. The median age of patients was 58 years, 43% were female; 67% were White and 16% were Black. The median Hb at baseline was 10.4 g/dL. Among randomized patients, 89% were receiving hemodialysis and 11% peritoneal dialysis. Among key comorbidities, 42% reported a history of diabetes mellitus and 45% a history of CV disease. Median blood pressure was 134/74 mmHg. The median weekly dose of epoetin was 5751 units. Intravenous and oral iron uses were noted in 64 and 11% of patients, respectively. Baseline demographics were similar to patients with CKD G5D enrolled in other CVOTs and renal patient registries.. ASCEND-D will evaluate the efficacy and safety of daprodustat compared with epoetin alfa or darbepoetin alfa in the treatment of patients with anemia with CKD G5D.This trial is registered with ClinicalTrials.gov: NCT02879305. EudraCT Number: 2016-000541-31; Sponsor Protocol Number: 200807.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHIs) are as effective as erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels.. In this randomized, open-label, phase 3 trial, we assigned patients with CKD who were undergoing dialysis and who had a hemoglobin level of 8.0 to 11.5 g per deciliter to receive an oral HIF-PHI (daprodustat) or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). The two primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 (noninferiority margin, -0.75 g per deciliter) and the first occurrence of a major adverse cardiovascular event (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), with a noninferiority margin of 1.25.. A total of 2964 patients underwent randomization. The mean (±SD) baseline hemoglobin level was 10.4±1.0 g per deciliter overall. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.28±0.02 g per deciliter in the daprodustat group and 0.10±0.02 g per deciliter in the ESA group (difference, 0.18 g per deciliter; 95% confidence interval [CI], 0.12 to 0.24), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 2.5 years, a major adverse cardiovascular event occurred in 374 of 1487 patients (25.2%) in the daprodustat group and in 394 of 1477 (26.7%) in the ESA group (hazard ratio, 0.93; 95% CI, 0.81 to 1.07), which also met the prespecified noninferiority margin for daprodustat. The percentages of patients with other adverse events were similar in the two groups.. Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-D ClinicalTrials.gov number, NCT02879305.).

Topics: Aged; Anemia; Barbiturates; Cardiovascular Diseases; Darbepoetin alfa; Epoetin Alfa; Female; Glycine; Hematinics; Hemoglobins; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; Intention to Treat Analysis; Male; Middle Aged; Myocardial Infarction; Renal Dialysis; Renal Insufficiency, Chronic; Stroke

Erythropoietin stimulating agent (ESA) has been standard of care in treating renal anaemia for the past 20 years. Many patients have limited access to ESA in view of long-term costs leading to suboptimal ESA dosage. Biosimilar epoetin is a potential cost-effective alternative to originator for optimal renal anaemia management.. To determine efficacy and safety of PDA10 in treating renal anaemia in haemodialysis patients, in comparison to the originator epoetin-α, Eprex®.. A phase 3, multicentre, multi-national, double-blind, randomised, active-controlled and parallel group study conducted over 40 weeks in Malaysia and Korea. End stage kidney disease patients undergoing regular haemodialysis who were on erythropoietin treatment were recruited. The study has 3 phases, which included a 12-week titration phase, followed by 28-week double-blind treatment phase and 24-week open-label extension phase.. The PDA10 and Eprex® were shown to be therapeutically equivalent (p < 0.0001) with mean absolute change in haemoglobin from baseline of - 0.176 (± 0.91) g/dl and - 0.118 (± 1.114) g/dl, respectively. Weekly dose change was 10.01 IU/kg/week in PDA10 group and 10.30 IU/kg/week in Eprex® group, which has no significant difference. There were no significant differences in the safety profile between PDA10 and Eprex® groups.. This study has confirmed the therapeutic equivalence between PDA10 and Eprex® in terms of efficacy, dosage requirement and safety profile in haemodialysis patients with renal anaemia.. The study was registered with the National Medical Research Register ( NMRR-13-400-16313 ). This study has been registered retrospectively with Clinical Research Information Service ( CRiS ), Republic of Korea on 25 March 2021.

Topics: Adult; Aged; Anemia; Double-Blind Method; Epoetin Alfa; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Treatment Outcome

We evaluated the efficacy and safety of roxadustat versus epoetin alfa for the treatment of chronic kidney disease-related anemia in patients new to dialysis.. HIMALAYAS was a Phase 3, open-label, epoetin alfa-controlled trial. Eligible adults were incident to hemodialysis/peritoneal dialysis for 2 weeks to ≤4 months prior to randomization and had mean hemoglobin (Hb) ≤10.0 g/dL. Primary endpoints were mean Hb (g/dL) change from baseline averaged over Weeks 28-52 regardless of rescue therapy [non-inferiority criterion: lower limit of 95% confidence interval (CI) for treatment difference >-0.75] and percentage of patients achieving an Hb response between Weeks 1 and 24 censored for rescue therapy (non-inferiority margin for between-group difference -15%). Adverse events were monitored.. The intent-to-treat population included patients randomized to roxadustat (n = 522) or epoetin alfa (n = 521). Mean (standard deviation) Hb changes from baseline averaged over Weeks 28-52 were 2.57 (1.27) and 2.36 (1.21) in the roxadustat and epoetin alfa groups. Roxadustat was non-inferior [least squares mean difference: 0.18 (95% CI 0.08, 0.29)] to epoetin alfa. Percentages of patients with an Hb response were 88.2% and 84.4% in the roxadustat and epoetin alfa groups, respectively. Roxadustat was non-inferior to epoetin alfa [treatment-group difference 3.5% (95% CI -0.7%, 7.7%)]. Adverse event rates were comparable between treatment groups.. Roxadustat was efficacious for correcting and maintaining Hb levels compared with epoetin alfa. Roxadustat had an acceptable safety profile.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Glycine; Hematinics; Hemoglobins; Humans; Isoquinolines; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Hematologic toxicities are one of the greatest challenges in adjuvant chemotherapy for breast cancer. This analysis of the ADEBAR trial aims to evaluate application and effect of granulocyte colony-stimulating factor (G-CSF) and epoetin alfa (EPO) on hematologic parameters and fatigue in patients with breast cancer during chemotherapy.. In the ADEBAR trial, 1493 patients with node-positive primary breast cancer were randomized to either 6 × 5-fluorouracil, epirubicin, and cyclophosphamide (FEC120) or 4 × epirubicin and cyclophosphamide followed by 4 × docetaxel (EC-DOC). Co-medication with G-CSF or EPO was applied to treat chemotherapy-induced leukopenia or anemia. Fatigue was assessed at baseline and after one-half of the chemotherapy.. In total, 899 patients could be included in the analysis. There was no evidence for an association between leucocyte or hemoglobin levels and application of G-CSF and EPO in the preceding cycle, respectively. Hemoglobin levels (B = -0.41; P < .001) were affected by treatment regimen. Fatigue during chemotherapy was mostly affected by the level of fatigue before the start of chemotherapy (B = 0.41; P < .001). Patients with G-CSF application in the preceding cycle showed an increased fatigue score (B = 5.43; P = .02).. We showed that fatigue during adjuvant chemotherapy was mostly affected by the level of fatigue present before the start of chemotherapy. This result suggests that the level of fatigue before the start of treatment should be included as an important factor when deciding on type and toxicity of chemotherapy in early breast cancer.

Topics: Adolescent; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Epoetin Alfa; Fatigue; Female; Granulocyte Colony-Stimulating Factor; Hemoglobins; Humans; Leukocyte Count; Leukopenia; Middle Aged; Neoplasm Staging; Prospective Studies; Quality of Life; Severity of Illness Index; Young Adult

treatment of erythropoietin (EPO) is essential in chronic kidney disease (CKD) patients to maintain optimal hemoglobin (Hb) level. Renogen is a biosimilar epoetin-α, and Eprex is the originator epoetin-α. This study aimed to compare the efficacy and tolerance of Renogen with Eprex in CKD anemia.. Renogen and Eprex were compared in a randomized (2:1), open-label study for 8 weeks, proceeded by 4 weeks adjustment (maintenance) phase, in anemic CKD patients undergoing HD in Cipto Mangunkusumo General Hospital, Jakarta, from June 2017 to October 2018.. a total of 45 patients (31 received biosimilar EPO and 14 received originator EPO) were included in the study.  At baseline, mean (SD) Hb levels were 10.9 (0.74) g/dL and 10.9 (0.61) g/dL in biosimilar and originator EPO groups, respectively. At end of study (8 weeks), mean (SD) Hb levels were 10.5 (1.28) g/dL and 11.0 (1.13) g/dL in biosimilar EPO and originator EPO groups, respectively.  The proportion of patients with Hb levels maintained within the target range (>10 g/dL) during 8 weeks randomization phase were 58.1% and 71.4% in biosimilar EPO and originator EPO, respectively (p=0.60; NS). There were no significant difference in epoetin dose between the 2 groups, and there was no drug-related adverse event in either group.. Hb level at >10 g/dL could be maintained for 8 weeks of treatment with both originator and biosimilar EPO (more consistent with originator EPO and more fluctuations with biosimilar EPO), with similar epoetin dose and no drug-related adverse event.

Topics: Adult; Anemia; Biosimilar Pharmaceuticals; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Indonesia; Injections, Intravenous; Male; Middle Aged; Renal Insufficiency, Chronic; Treatment Outcome

Molidustat, a novel hypoxia-inducible factor-prolyl hydroxylase inhibitor, is being investigated for the treatment of anemia associated with chronic kidney disease (CKD). The efficacy and safety of molidustat were recently evaluated in three 16-week phase 2b studies. Here, we report the results of two long-term extension studies of molidustat.. Both studies were parallel-group, open-label, multicenter studies of ≤36 months' duration, in patients with anemia due to CKD, and included an erythropoiesis-stimulating agent as active control. One study enrolled patients not receiving dialysis (n = 164), and the other enrolled patients receiving hemodialysis (n = 88). The primary efficacy variable for both studies was change in blood hemoglobin (Hb) level from baseline to each post-baseline visit, and safety outcomes included adverse events (AEs).. In patients not on dialysis, the mean ± SD Hb concentrations at baseline were 11.28 ± 0.55 g/dL for molidustat and 11.08 ± 0.51 g/dL for darbepoetin. The mean ± SD blood Hb concentrations throughout the study (defined as mean of each patient's overall study Hb levels) were 11.10 ± 0.508 and 10.98 ± 0.571 g/dL in patients treated with molidustat and darbepoetin, respectively. Similar proportions of patients reported at least one AE in the molidustat (85.6%) and darbepoetin (85.7%) groups. In patients on dialysis, mean ± SD Hb levels at baseline were 10.40 ± 0.70 and 10.52 ± 0.53 g/dL in the molidustat and epoetin groups, respectively. The mean ± SD blood Hb concentrations during the study were 10.37 ± 0.56 g/dL in the molidustat group and 10.52 ± 0.47 g/dL in the epoetin group. Proportions of patients who reported at least one AE were 91.2% in the molidustat group and 93.3% in the epoetin group.. Molidustat was well tolerated for up to 36 months and appears to be an effective alternative to darbepoetin and epoetin in the long-term management of anemia associated with CKD.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Long-Term Care; Male; Middle Aged; Pyrazoles; Renal Dialysis; Renal Insufficiency, Chronic; Time Factors; Treatment Outcome; Triazoles

Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis.. In a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to -1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values.. A total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (±SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7±1.1 g per deciliter) than epoetin alfa (0.5±1.0 g per deciliter) and was statistically noninferior (difference, 0.2±1.2 g per deciliter; 95% confidence interval [CI], -0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 μg per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, -22 mg per deciliter; 95% CI, -29 to -16), as was the decrease in low-density lipoprotein cholesterol (difference, -18 mg per deciliter; 95% CI, -23 to -13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, -64.8 to -13.6), as compared with 2.3 ng per milliliter (95% CI, -51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group.. Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652806.).

Topics: Adult; Aged; Analysis of Variance; Anemia; Cholesterol; Double-Blind Method; Epoetin Alfa; Female; Glycine; Hematinics; Hemoglobins; Humans; Hyperkalemia; Hypertension; Hypoxia-Inducible Factor-Proline Dioxygenases; Isoquinolines; Male; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic

This is a post-hoc analysis evaluating erythropoiesis stimulating agents' (ESA) related costs while using an additional ultrafilter (Estorclean PLUS) to produce ultrapure dialysis water located within the fluid pathway after the treatment with reverse osmosis and before the dialysis machine. Twenty-nine patients (19 treated with epoetin alfa and 10 with darboepoetin alfa) were included in the analysis. We showed to gain savings of 210 € per patient (35 € per patient each month) with epoetin alfa during the experimental period of 6 months, compared to the control period and of 545 € per patient (90 € per patient each month) with darboepoetin alfa. Estorclean PLUS had a cost of 600 € (25 € per month per each patient) and was used for 6 months. Intravenous iron therapy with sodium ferrigluconate had a cost of 0,545 €/62,5 mg. In conclusion, during the experimental period with the use of Estorclean, we obtained global savings of 11 € per patient per month with epoetin alfa and 30 € per patient per month with darboepoetin alfa to treat anemia in dialysis patients.

Topics: Aged; Aged, 80 and over; Anemia; Cost Savings; Costs and Cost Analysis; Cross-Over Studies; Darbepoetin alfa; Distillation; Epoetin Alfa; Female; Ferric Compounds; Filtration; Hematinics; Hemodialysis Solutions; Hemoglobins; Humans; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Water

Comparability studies used to assess a proposed manufacturing change for a biological product include sensitive analytical studies to confirm there are no significant differences in structural or functional attributes that may contribute to clinically meaningful changes in efficacy or safety. When a proposed change is relatively complex or when clinically relevant differences between the product before and after the change cannot be ruled out based on analytical studies, nonclinical and clinical bridging studies are generally required to confirm overall comparability. In this study, we report findings from a comparability assessment of epoetin alfa before and after a proposed manufacturing process change. Although differences in glycosylation attributes were observed, these were initially believed to be irrelevant to the product's pharmacology. This assumption was initially supported via nonclinical and clinical pharmacology studies, but a clinically meaningful difference in potency was ultimately observed in a phase 3 clinical study conducted in a sensitive patient population using a sensitive study design. These results indicate that the nonclinical assessments of structure-function relationships were insufficiently sensitive to identify clinically relevant differences resulting from differences in the glycosylation profile. This case study highlights important findings that may be relevant in the development of biosimilar epoetin alfa products.

Topics: Anemia; Animals; Biosimilar Pharmaceuticals; Drug Approval; Epoetin Alfa; Glycosylation; Hematinics; Humans; Mice; Mice, SCID; Recombinant Proteins; Renal Insufficiency, Chronic; Research Design; Structure-Activity Relationship

Erythropoiesis-stimulating agents are first choice for treating anemia in low-risk MDS. This double-blind, placebo-controlled study assessed the efficacy and safety of epoetin-α in IPSS low- or intermediate-1 risk (i.e., low-risk) MDS patients with Hb ≤ 10.0 g/dL, with no or moderate RBC transfusion dependence (≤4 RBC units/8 weeks). Patients were randomized, 2:1, to receive epoetin-α 450 IU/kg/week or placebo for 24 weeks, followed by treatment extension in responders. The primary endpoint was erythroid response (ER) through Week 24. Dose adjustments were driven by weekly Hb-levels and included increases, and dose reductions/discontinuation if Hb > 12 g/dL. An independent Response Review Committee (RRC) blindly reviewed all responses, applying IWG-2006 criteria but also considering dose adjustments, drug interruptions and longer periods of observation.A total of 130 patients were randomized (85 to epoetin-α and 45 to placebo). The ER by IWG-2006 criteria was 31.8% for epoetin-α vs 4.4% for placebo (p < 0.001); after RRC review, the ER was 45.9 vs 4.4% (p < 0.001), respectively. Epoetin-α reduced RBC transfusions and increased the time-to-first-transfusion compared with placebo.Thus, epoetin-α significantly improved anemia outcomes in low-risk MDS. IWG-2006 criteria for ER may require amendments to better apply to clinical studies.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Treatment Outcome

This study was conducted to compare the safety and efficacy of intravenous epoetin alfa-epbx, an epoetin alfa biosimilar, to epoetin alfa in patients on hemodialysis with ESKD and anemia.. In this 24-week, multicenter, double-blind comparative efficacy and safety study, 612 patients on hemodialysis with ESKD and anemia who had stable hemoglobin and were receiving stable doses of intravenous epoetin alfa were randomized (1:1) to intravenous epoetin alfa or epoetin alfa-epbx. Dosing was adjusted according to the epoetin alfa prescribing information. The coprimary efficacy end points were the least squares mean difference between the two treatments in mean weekly hemoglobin level and mean weekly epoetin dose per kilogram of body weight during the last 4 weeks of treatment.. The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly hemoglobin was -0.12 g/dl and the 95% confidence interval (-0.25 to 0.01) was contained within the prespecified equivalence margin (-0.5 to 0.5 g/dl). The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly epoetin dose per kilogram of body weight was 0.37 U/kg per week, and the 95% confidence interval (-10.40 to 11.13) was contained within the prespecified equivalence margin (-45 to 45 U/kg per week). Incidences of adverse events (77.1% versus 75.3%), serious adverse events (24.9% versus 27.0%), and deaths (. This 24-week, comparative, clinical trial in patients on hemodialysis with ESKD and anemia demonstrated there is no clinically meaningful difference in efficacy or safety between epoetin alfa-epbx and epoetin alfa.

Topics: Administration, Intravenous; Anemia; Biosimilar Pharmaceuticals; Double-Blind Method; Epoetin Alfa; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

For patients with anemia undergoing hemodialysis, erythropoiesis-stimulating agents (ESAs) are typically dosed via precise algorithms. Using one such algorithm, we assessed the maintenance of hemoglobin levels in patients switched from epoetin alfa reference product (Epogen®) to epoetin alfa-epbx (RetacritTM; a biosimilar to US-licensed Epogen®/Procrit®).. This randomized, open-label, non-inferiority study was conducted at Fresenius Medical Care North America (FMCNA) hemodialysis centers. Patients with anemia and chronic kidney disease undergoing maintenance hemodialysis and receiving routine intravenous (IV) Epogen® were randomized 1: 1 to switch to IV RetacritTM or continue standard-of-care (Epogen®) for 24 weeks, using analogous versions of the FMCNA ESA-dosing algorithm. The primary endpoint was the proportion of time patients' hemoglobin was 9-11 g/dL during weeks 17-24.. Of 432 randomized patients, 418 received treatment (RetacritTM, n = 212; standard-of-care, n = 206) and comprised the full analysis set. A similar proportion of patients discontinued from each arm. The proportion of time patients' hemoglobin was within the target range was 61.9% (95% CI 57.5-66.2) in the RetacritTM arm and 63.3% (95% CI 58.7-67.7) in the standard-of-care arm. The difference in proportions between treatment arms was -1.4% (95% CI -7.6 to 4.9), and the lower bound of the confidence interval was within the pre-specified non-inferiority margin of -12.5%. There was no statistically significant difference between arms in the mean change from baseline in the weekly mean ESA dose during weeks 17-24, and no clinically relevant differences in safety outcomes.. Switching to RetacritTM was non-inferior to continuing -Epogen® in maintaining hemoglobin levels in patients receiving hemodialysis, when both ESAs were dosed using a specified algorithm (ClinicalTrials.gov, NCT02504294).

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Anemia; Biosimilar Pharmaceuticals; Dose-Response Relationship, Drug; Drug Dosage Calculations; Drug Substitution; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Treatment Outcome; Young Adult

Anemia is one of the most prevalent complications in patients with chronic kidney disease, which is believed to be caused by the insufficient synthesis of erythropoietin by the kidney. This phase III study aimed to compare the efficacy and safety of CinnaPoietin® (epoetin beta, CinnaGen) with Eprex® (epoetin alfa, Janssen Cilag) in the treatment of anemia in ESRD hemodialysis patients.. In this randomized, active-controlled, double-blind, parallel, and non-inferiority trial, patients were randomized to receive either CinnaPoietin® or Eprex® for a 26-week period. The primary endpoints of this study were to assess the mean hemoglobin (Hb) change during the last 4 weeks of treatment from baseline along with the evaluation of the mean weekly epoetin dosage per kilogram of body weight that was necessary to maintain the Hb level within 10-12 g/dL during the last 4 weeks of treatment. As the secondary objective, safety was assessed along with other efficacy endpoints.. A total of 156 patients were included in this clinical trial. There was no statistically significant difference between treatment groups regarding the mean Hb change (p = 0.21). In addition, the mean weekly epoetin dosage per kg of body weight for maintaining the Hb level within 10-12 g/dL showed no statistically significant difference between treatment arms (p = 0.63). Moreover, both products had comparable safety profiles. However, the incidence of Hb levels above 13 g/dL was significantly lower in the CinnaPoietin® group.. CinnaPoietin® was proved to be non-inferior to Eprex® in the treatment of anemia in ESRD hemodialysis patients. The trial was registered in Clinicaltrials.gov (NCT03408639).

Topics: Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Treatment Outcome

HX575 (biosimilar epoetin alfa) was approved in Europe in 2007 for the treatment of chronic kidney disease (CKD)-related anemia. This study assessed the clinical equivalence of HX575 with the US-licensed reference epoetin alfa (Epogen®/Procrit®, Amgen/Janssen) following subcutaneous (SC) administration in dialysis patients with CKD-related anemia.. This randomized, double-blind, parallel-group, multicenter study (NCT01693029) was conducted at 49 US clinical sites. Eligible patients were aged ≥18 years, had end-stage renal disease, were on hemodialysis or peritoneal dialysis for ≥6 months (or ≥12 months in the case of a failed kidney transplant), and were receiving treatment with stable SC doses of epoetin alfa. Eligible patients also had mean hemoglobin (Hb) concentration between 9.0 and 11.5 g/dL during the screening period. The primary endpoint was the mean absolute change in Hb concentration between the screening/baseline period (week-4 to week-1) and the evaluation period (weeks 21 to 28).. Hb values at the end of the evaluation period and the Hb change from baseline to evaluation period were similar between treatment groups. The estimated difference between groups in mean absolute change in Hb concentration was -0.093 g/dL, with 90% CI (-0.23 to 0.04) entirely within the pre-specified equivalence limits (-0.5 to 0.5 g/dL). The safety profile of each medicine was similar and as expected in dialysis patients, and neither method of treatment led to the development of neutralizing, clinically relevant antibodies.. SC HX575 in dialysis patients with renal anemia was therapeutically equivalent to the reference medicine in terms of maintaining stable Hb levels and safety.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Biosimilar Pharmaceuticals; Double-Blind Method; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Therapeutic Equivalency; Treatment Outcome; United States; Young Adult

Hemodialysis (HD) patients often show impaired response to erythropoiesis-stimulating agents (ESAs). Extended HD membrane permeability may potentially improve ESA response.. Twenty-four prevalent HD patients were randomly assigned to 12 weeks use of high cut-off (HCO) membrane (in every second dialysis treatment) or continued treatment with high-flux membrane. We monitored changes in hemoglobin (Hb), ESA dose, and key biochemical markers.. The Hb level increased in the study group (from 11.6 ± 1.0 to 12.5 ± 1.5 g/dl; p = 0.038) but was stable in the control group. Variation over time in ESA dose and ESA resistance index did not differ between groups. HCO membrane usage for 12 weeks led to decreased hepcidin level, from 303 ± 189 to 157 ± 83 ng/ml (p = 0.024); serum albumin level decreased and stabilized 15 ± 6% below baseline.. These results indicate that use of a more permeable dialysis membrane may improve ESA responsiveness in iron-replete HD patients. Extensive albumin removal may preclude long-term use of the HCO membrane.

Topics: Aged; Anemia; C-Reactive Protein; Drug Resistance; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Hepcidins; Humans; Interleukin-6; Kidney Failure, Chronic; Male; Membranes, Artificial; Middle Aged; Permeability; Pilot Projects; Recombinant Proteins; Renal Dialysis; Serum Albumin

Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin.. Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study.. Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa.. Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited.. Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2).. Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset).. Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (P<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed with epoetin alfa. No safety concerns were raised.. Short treatment duration and small sample size.. In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Female; Glycine; Hematinics; Humans; Isoquinolines; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Time Factors; Treatment Outcome; Young Adult

An open-label, noninferiority study to evaluate the impact of epoetin alfa (EPO) on tumor outcomes when used to treat anemia in patients receiving chemotherapy for metastatic breast cancer.. Women with hemoglobin ≤ 11.0 g/dL, receiving first- or second-line chemotherapy for metastatic breast cancer, were randomly assigned to EPO 40,000 IU subcutaneously once a week or best standard of care. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, time to tumor progression, overall response rate, RBC transfusions, and thrombotic vascular events.. In 2,098 patients randomly assigned, median PFS (based on investigator-determined disease progression [PD]) was 7.4 months in both groups (hazard ratio [HR], 1.089; 95% CI, 0.988 to 1.200); upper bound exceeded prespecified noninferiority margin of 1.15. Median PFS per independent review committee-determined PD was 7.6 months in both groups (HR, 1.028; 95% CI, 0.922 to 1.146); upper bound did not exceed prespecified noninferiority margin. Median overall survival at clinical cutoff (1,337 deaths) was 17.2 months in the EPO and 17.4 months in the best standard of care group (HR, 1.057; 95% CI, 0.949 to 1.177), median time to tumor progression was 7.5 months in both groups (HR, 1.094; 95% CI, 0.991 to 1.209), and overall response rate was 50% versus 51% (odds ratio, 0.950; 95% CI, 0.799 to 1.130). RBC transfusions were 5.8% versus 11.4% (P < .001), and thrombotic vascular events were 2.8% versus 1.4% (P = .038), respectively.. The primary end point, PFS based on investigator-determined PD, did not meet noninferiority criteria. As a consistency assessment with the primary finding, PFS based on independent review committee-determined PD met noninferiority criteria. Overall, this study did not achieve noninferiority objective in ruling out a 15% increased risk in PD/death. RBC transfusion should be the preferred approach for the management of anemia in this population.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Progression; Drug Administration Schedule; Epoetin Alfa; Female; Hematinics; Humans; Kaplan-Meier Estimate; Middle Aged; Odds Ratio; Quality of Life; Standard of Care; Treatment Outcome

Anemia is a frequent complication in patients with chronic kidney disease. However, human recombinant erythropoietin (rHu-EPO) has revolutionized the management of anemia in chronically dialyzed patients. Epomax ® is a new rHu-EPO alfa manufactured in Tunisia (Medis Laboratories). The aim of this study was to evaluate the efficacy and tolerance of Epomax ® in chronic hemodialysis (HD) patients in a phase-III, multicenter, clinical trial. Fiftythree HD patients (mean age 47.7 ± 13 years) who received a stable dose of rHu-EPO (Hemax ® , a rHu-EPO alfa manufactured by Biosidus Laboratories) subcutaneously were switched to Epomax ® via the same route of administration. At baseline, the mean systolic pressure was 132 ± 18 mm Hg and the mean diastolic pressure was 79 ± 8 mm Hg. The mean blood hemoglobin was 10.2 g/dL and the median ferritin level was 667 ng/mL. After a follow-up of 43 days, the mean blood hemoglobin was 10.5 g/dL under the effect of Epomax ® . There was no significant difference in the mean hemoglobin levels between the treatments with both drugs. Few adverse events were reported during the study. We conclude that Epomax ® was effective at maintaining the hemoglobin levels at target concentrations and was well tolerated in HD patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Biosimilar Pharmaceuticals; Blood Pressure; Drug Substitution; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic; Therapeutic Equivalency; Tunisia

This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa).. The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm.. A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms.. This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Carcinoma, Squamous Cell; Chemoradiotherapy; Combined Modality Therapy; Disease-Free Survival; Epoetin Alfa; Erythropoietin; Female; Head and Neck Neoplasms; Hematinics; Hemoglobin A; Humans; Male; Middle Aged; Recombinant Proteins; Squamous Cell Carcinoma of Head and Neck; Time Factors

In hemodialysis (HD) patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA) hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI).. Patients on HD with low serum zinc levels (<65 μg/dL) were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc) (n = 35) and the control group (no supplementation) (n = 35) for 12 months. All the 70 patients had been taking epoetin alpha as treatment for renal anemia. ERI was measured with the following equation: Weekly ESA dose (units)/dry weight (kg)/hemoglobin (g/dL).. There were no significant changes in hemoglobin levels within groups or between the control and polaprezinc groups during the study period. Although reticulocyte counts were increased immediately after zinc supplementation, this change was transient. Serum zinc levels were significantly increased and serum copper levels were significantly decreased in the polaprezinc group after three months; this persisted throughout the study period. Although there was no significant change in the serum iron or transferrin saturation levels in the polaprezinc group during the study period, serum ferritin levels significantly decreased following polaprezinc treatment. Further, in the polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months and nine months, respectively, as compared with the baseline value. Multiple stepwise regression analysis revealed that the change in the serum zinc level was an independent predictor of lowered ERI.. Zinc supplementation reduces ERI in patients undergoing HD and may be a novel therapeutic strategy for patients with renal anemia and low serum zinc levels.

Topics: Administration, Oral; Aged; Anemia; Carnosine; Copper; Dietary Supplements; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Organometallic Compounds; Regression Analysis; Renal Dialysis; Trace Elements; Zinc; Zinc Compounds

Erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) increase hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients with cancer chemotherapy-associated anemia (CAA). Extended-interval ESA dosing (administration less than once weekly) is common with DA, but previous studies suggested that EA might also be administered less often than weekly. In this multicenter prospective trial, 239 CAA patients with Hb <10.5 g/dL were randomized to receive EA 40,000 U subcutaneously once weekly ("40K" arm), EA 80,000 U every 3 weeks ("80K"), EA 120,000 U every 3 weeks ("120K" arm), or DA 500 mcg every 3 weeks ("DA"), for 15 weeks. The primary endpoint was the proportion of patients achieving Hb ≥ 11.5 g/dL or increment of Hb > 2.0 g/dL from baseline without transfusion. Secondary endpoints included transfusion requirements, adverse events (AEs), and patient-reported outcomes (PROs). There were no significant differences between treatment arms in the proportion of patients achieving Hb response (68.9% for 40K, 61.7% for 80K, 65.5% for 120K, and 66.7% for DA; P > 0.41 for all comparisons) or requiring RBC transfusion, but the median Hb increment from baseline was higher in the 40K and DA arms compared to the two extended dosing EA arms, and Hb response was achieved soonest in the weekly EA arm. There were no differences in PROs or AEs. The FDA-approved schedules tested-weekly EA 40,000 U, and every 3 week DA 500 mcg-are reasonable standards for CAA therapy.

Topics: Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Male; Neoplasms

Indoxyl sulfate (IS) suppresses erythropoietin (EPO) activity and exerts renal damage. The oral adsorbent AST-120 reduces IS load and has antioxidant and renoprotective properties; however, its roles in the treatment of anemia remain unclear in chronic kidney disease (CKD) patients.. Fifty-one Stage 5 predialysis CKD patients with hemoglobin <10 g/dL were randomly assigned to receive two period treatments with AST-120 plus once-monthly administration of continuous EPO receptor activator (CERA, A) and CERA alone (B), with a 4-week washout period in between. Mean changes of serum creatinine, estimated glomerular filtration rate (eGFR) and hemoglobin levels from the baseline were compared between two treatments.. The baseline and postintervention mean creatinine levels were 5.48 and 5.36 mg/dL in the Treatment A, and 5.14 mg/dL and 5.61 g/dL in the Treatment B group, respectively (treatment effect P = 0.025, period effect P = 0.467, carryover effect P = 0.384). The baseline and postintervention mean hemoglobin levels were 9.27 and 10.47 g/dL in the Treatment A, and 9.63 g/dL and 9.54 g/dL in the Treatment B group, respectively (treatment effect P = 0.039, period effect P = 0.001, carryover effect P = 0.060). Use of AST-120 significantly reduced IS and p-cresyl sulfate (PCS) levels. Hierarchical regression showed that eGFR was an independent predictor for hemoglobin after adjustment of serum free IS and PCS levels (B = 0.049, P = 0.005).. Use of adjuvant AST-120 may improve renal function and hemoglobin levels than use of CERA alone in late-stage CKD patients. The change of eGFR might play an intermediate role between serum IS/PCS and improve hemoglobin levels. The finding offered insight into novel therapeutic strategies of anemia for late-stage CKD patients.

Topics: Adult; Aged; Anemia; Carbon; Cross-Over Studies; Drug Synergism; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Indican; Kidney; Kidney Failure, Chronic; Male; Microspheres; Middle Aged; Oxides; Polyethylene Glycols; Recombinant Proteins

To study correlation between concentration of pathological cytokines and erythropoietin inpatients with chronic heart failure anemic syndrome and also to prove importance of this communication for need of appointment erythropoietin excitants.. 94 patients with chronic heart failure of New York Heart Association (NYHA) class III-IV a left ventricular ejection fraction of 40% or less withanemia w ere idied in inveslain (58 males, 36 females). Anemia was detected when hemoglobin (b) was less than 120 g/l in males and less than in females. 46 patients received traditional treatment of CHF (I group) and 48 patients were treated additionally with erythropoietin (EPO) (II group). Percutaneous EPO 50 IU monthly to patients without iron deficiency for a period of 6 months. Echocardiography parameters, plasma NT and pro-BNP, cytokines, EPO, feritin and 6-minute walking test were assessed at baseline and after treatment.. in patients with CHF and anemia in II group erythropoietin treatment increased Hb levels by 22.4% (p < 0.05) and erythropoietin serum levels by 29.3 +/- 14.3 IU/ml (p < 0.001). Increased erythropoietin level was associated with decrease of cytokines levels: IL 1 by 36.6% (p < 0.001), IL 6 by 54.3% (p < 0.05), TNF alpha by 48.3% (p < 0.05) compared with patients in I group. In erythropoietin-treated patients there is a significant increase of LVEF by 19.04% (p < 0.05) compared with patients from I group. A greater 6-minute distance walked on exercise testing increased by 76.6% (p < 0.05) after treatment with erythropoieitin.. Correction of anemia in patients with chronic heart failure with percutaneous erythropoietin injections 50 IU monthly for 6 month period to improve erythropoietin deficit and cytokines aggression and associated anemia, symptoms and quaity of life.

Topics: Anemia; Chronic Disease; Cytokines; Epoetin Alfa; Erythropoietin; Exercise Test; Female; Heart Failure; Hemoglobins; Humans; Interleukin-1; Male; Middle Aged; Recombinant Proteins; Treatment Outcome; Tumor Necrosis Factor-alpha; Ventricular Function, Left

Induction chemotherapy is associated with anemia in non-small cell lung cancer (NSCLC) patients undergoing radiotherapy. This randomized, open-label study compared the effect of sequential radiochemotherapy (RCHT) versus RCHT + epoetin alfa (RCHT + EPO), with respect to 2-year overall survival (OS).. Patients ⩾18 years received sequential RCHT; one arm also received EPO (chemotherapy day 1, when Hb<12 g/dL). Kaplan-Meier analysis with log-rank test, and Cox-regression methods were performed.. Of the 385 patients randomized (RCHT + EPO: n = 195; RCHT: n = 190), 78 (RCTH + EPO: 46 [23.6%]; RCHT: 32 [16.8%]) were anemic at baseline. Two-year OS was higher in RCHT + EPO-treated versus RCHT-treated (28.5% [95% CI: 22.2-35.1%] versus 20.6% [95% CI: 15.1-26.8%] [p = 0.2278]), and requirement for RBC transfusion was lower (24/195 [12.3%] versus 61/190 [32.1%]). In anemic (baseline) patients (post hoc analysis), median survival was shorter in RCTH-treated (212 days) versus RCHT + EPO-treated (343 days) (Hazard ratio = 1.62 [95% CI: 0.99-2.63], p = 0.0525). Adverse events were documented in 72.7% (RCHT + EPO: 75.0%; RCHT: 70.5%) patients, and thrombovascular events (TVEs) in 45 patients (RCHT + EPO: 16.7%; RCHT: 7.9%; p = 0.0099).. A statistically non-significant trend for 2-year OS was observed in a sub-group of EPO-treated NSCLC-patients with baseline anemia, although this trend was not maintained in the overall population with inoperable NSCLC.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Recombinant Proteins; Vinblastine; Vinorelbine

Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation).. The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians' discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495.. The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9±1.2 and 10.96±1.2 g/dL (p = 0.89) in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar.. The epoetin formulations tested in this study are equivalent in efficacy and safety.

Topics: Adult; Aged; Anemia; Biosimilar Pharmaceuticals; Brazil; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Iron; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome

Vitamin D insufficiency is related to erythropoietin resistance in chronic kidney disease (CKD). This study was conducted to evaluate the effect of ergocalciferol on the dose of erythrocyte-stimulating agent (ESA) administered to children with CKD stage 5 and vitamin D insufficiency.. Twenty patients aged <18 years with CKD stages 5 or 5D and vitamin D insufficiency were divided into two groups. During the 12-week study, ten patients received oral ergocalciferol (treatment) whereas the other ten patients did not (control). The ESA dosage was recorded monthly.. There were no significant differences in demographic data, ESA dosages, and laboratory data, including corrected calcium, phosphorus, parathyroid hormone, hemoglobin, ferritin, 25-hydroxyvitamin D (25D), and transferrin saturation levels, between the two groups at baseline. At the completion of the study, serum 25D levels in the treatment group were significantly increased from baseline (p = 0.02) and were significantly higher than the serum 25D levels in the controls (p < 0.005). The ESA dosage in the treatment group was significantly decreased when compared to baseline (p = 0.04).. Vitamin D deficiency should be routinely detected and treated. Our results show that the administration of ergocalciferol in conjunction with 1,25-dihydroxyvitamin D3 reduced the dose of ESA required to treat children with CKD stages 5 and 5D and may decrease erythropoietin resistance.

Topics: Administration, Oral; Adolescent; Analysis of Variance; Anemia; Biomarkers; Child; Child, Preschool; Drug Resistance; Epoetin Alfa; Ergocalciferols; Erythropoietin; Female; Hematinics; Humans; Male; Prospective Studies; Recombinant Proteins; Renal Insufficiency, Chronic; Severity of Illness Index; Thailand; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Recombinant erythropoietin has become a routine component of care of patients with chronic kidney disease reducing the need for blood transfusions but raising the risks for cardiovascular events. We undertook this secondary analysis of subjects enrolled in the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) trial to examine the interrelationships between epoetin-alfa maintenance doses utilized and achieved hemoglobin (Hb) irrespective of treatment target and randomized allocation.. We performed a post hoc analysis from the CHOIR trial. Inclusion criteria were Hb <11.0 g/dl and estimated glomerular filtration rates of 15-50 ml/min/1.73 m(2). To be included in the present analysis, subjects needed to be free of the composite event at 4 months, receive epoetin-alfa, and have ≥1 postbaseline Hb measurement. The mean weekly dose of epoetin-alfa received up to the time of first event or censure was the main exposure variable, while the achieved Hb at month 4 was the confounder representing the subject's underlying response to treatment. The primary outcome was the composite of death, heart failure hospitalization, stroke, or myocardial infarction. A Cox proportional hazard regression model was used in time-to-event analysis.. Among 1,244 subjects with complete data, the average weekly dose of epoetin-alfa ranged 143.3-fold from 133 to 19,106 units/week at the time of first event or censure. Cox proportional hazard analysis found that those in the middle tertile of Hb achieved (>11.5 to <12.7 g/dl) and the lowest tertile of epoetin-alfa dose exposure level (<5,164 units/week) had the lowest risk. Irrespective of Hb achieved, the relative risk in the highest tertile (>10,095 units/week) of epoetin-alfa dose exposure level was significantly escalated (hazard ratios ranged from 2.536 to 3.572, p < 0.05, when compared to the group of middle Hb tertile and lowered dose tertile). In a multivariable model that adjusted for achieved Hb, albumin, cholesterol, age, prior heart failure, prior stroke, prior deep venous thrombosis, atrial fibrillation or malignancy, the average weekly dose had a significant (p = 0.005) relative risk of 1.067 per 1,000 units of epoetin-alfa for the primary end point.. In the CHOIR trial, average epoetin-alfa doses >10,095 units/week were associated with increased risks for cardiovascular events irrespective of the Hb achieved within the first 4 months of treatment. These data suggest the weekly epoetin-alfa dose and not the Hb achieved was a principal determinant in the primary outcome observed implicating a cardiovascular toxicity of this erythrocyte-stimulating agent.

Topics: Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Recombinant Proteins; Renal Insufficiency, Chronic; Risk Factors; Stroke; Treatment Outcome

Hyporesponders to erythropoietin-stimulating agents (ESAs) have been associated with an increased subsequent risk of death or cardiovascular events. We hypothesized that subjects who are hyporesponsive to erythropoietin alfa would have higher plasma volumes and lower red cell deficits than subjects who are responsive to therapy.. As part of a prospective, single blind, randomized, placebo-controlled study comparing erythropoietin alfa with placebo in older adults (n = 56) with heart failure and a preserved ejection fraction (HFPEF), we performed blood volume analysis with the use of an indicator dilution technique with (131)iodine-labeled albumin. We evaluated differences in plasma volumes and red cell volumes in hyporesponders (eg, <1 g/dL increase in hemoglobin within the first 4 weeks of treatment with erythropoetin alfa) compared with subjects who were responders and controls.. Nine of 28 subjects (32%) assigned to ESA were hyporesponders. Hyporesponders did not differ from responders nor control subjects by any baseline demographic, clinical, or laboratory parameter, including hemoglobin. Hyporesponders had a greater total blood volume expansion (1,264.7 ± 387 vs 229 ± 206 mL; P = .02) but less of a red cell deficit (-96.2 ± 126 vs -402.5 ± 80.6 mL; P = .04) and a greater plasma volume expansion (+1,360.8 ± 264.5 vs +601.1 ± 165.5 mL; P = .01). Among responders, the increase in hemoglobin with erythropoietin alfa was associated primarily with increases in red cell volume (r = 0.91; P < .0001) as well as a decline in plasma volume (r = -0.55; P = .06).. Among older adults with HFPEF and anemia, hyporesponders to erythropoietin alfa had a hemodilutional basis of their anemia, suggesting that blood volume analysis can identify a cohort likely to respond to therapy.

Topics: Aged; Aged, 80 and over; Anemia; Blood Volume; Epoetin Alfa; Erythrocyte Volume; Erythropoietin; Female; Heart Failure; Hemoglobins; Humans; Male; Middle Aged; Plasma Volume; Prospective Studies; Recombinant Proteins; Retrospective Studies; Single-Blind Method; Stroke Volume; Treatment Outcome

Erythropoietin stimulating agents (ESAs) is an active area of clinical investigation in heart failure (HF) but can cause hypertension and higher hemoglobin concentrations (Hb) that have been associated with adverse outcomes. We evaluated a dosing algorithm and potential confounders' effect on Hb and blood pressure (BP) in a clinical trial.. In an ongoing randomized, placebo controlled, single blind clinical trial of ESA (epoetin alfa) in anemic patients with HF and a preserved ejection fraction (HFPEF), Hb was measured weekly as was BP, weight and concomitant medical therapy. A repeated measure mixed model evaluated determinants of weekly changes in Hb and BP.. Among 45 subjects (78 ± 11 years, 67% women, EF = 57 ± 9%) with a total of 780 repeated weekly Hb measures, Hb significantly increased over time in those assigned to ESA (β = 0.933, P < 0.0001), compared to placebo. Dose (β = -0.108, P < 0.0001), patient weight (β = -0.016, P = 0.0037), diuretic use (β = -0.124, P = 0.0389), and time (β = 0.003, P = 0.0331), were all significantly associated with Hb change. Increased diuretic dose and weight change were significantly inversely associated with changes in Hb. ESA administration and dose were not significant determinants of absolute BP or changes in BP from baseline.. In addition to ESA dose and duration of therapy, factors indicative of volume status including weight and diuretic use are determinants of hemoglobin levels in HF subjects.. The currently employed dosing algorithm, which adjusts the administration of ESA based on the absolute hemoglobin and weekly change in hemoglobin increases Hb with relatively a low weekly dose of ESA without significant effects on BP.

Topics: Aged; Aged, 80 and over; Algorithms; Anemia; Biomarkers; Blood Pressure; Blood Volume; Confounding Factors, Epidemiologic; Diuretics; Drug Administration Schedule; Drug Dosage Calculations; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Hematinics; Hemoglobins; Humans; Male; Multivariate Analysis; New York City; Recombinant Proteins; Single-Blind Method; Stroke Volume; Time Factors; Treatment Outcome

Anemia is a common comorbidity in older adults with heart failure and a preserved ejection fraction and is associated with worse outcomes. We hypothesized that treating anemia with subcutaneous epoetin alfa would be associated with reverse ventricular remodeling and improved exercise capacity and health status compared with placebo.. Prospective, randomized, single-blind, 24-week study with blinded end point assessment among anemic (average hemoglobin of 10.4±1 g/dL) older adult patients (n=56; 77±11 years; 68% women) with heart failure and a preserved ejection fraction (ejection fraction=63±15%; B-type natriuretic peptide=431±366 pg/mL) was conducted. Treatment with epoetin alfa resulted in significant increases in hemoglobin (P<0.0001). Changes in end-diastolic volume (-6±14 versus -4±16 mL; P=0.67) at 6 months did not differ between epoetin alfa and placebo, but declines in stroke volume (-5±8 versus 2±10 mL; P=0.09) without significant changes in left ventricular mass were observed. Changes in 6-minute walk distance (16±11 versus 5±12 m; P=0.52) did not differ. Although quality of life improved by the Kansas City Cardiomyopathy Questionnaire and the Minnesota Living with Heart Failure Questionnaire in both cohorts, there were no significant differences between groups.. Administration of epoetin alfa to older adult patients with heart failure and a preserved ejection fraction compared with placebo did not change left ventricular end-diastolic volume and left ventricular mass nor did it improve submaximal exercise capacity or quality of life.. URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00286182.

Topics: Age Factors; Aged; Aged, 80 and over; Anemia; Biomarkers; Chi-Square Distribution; Comorbidity; Epoetin Alfa; Erythropoietin; Exercise Test; Exercise Tolerance; Female; Heart Failure; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; New York City; Prospective Studies; Quality of Life; Recombinant Proteins; Recovery of Function; Single-Blind Method; Stroke Volume; Surveys and Questionnaires; Time Factors; Treatment Outcome; Ventricular Remodeling; Walking

In the last ten years or so, there has been a steady increase in the number of patients with chronic kidney disease and those with end-stage renal failure who require some form of renal replacement therapy. Anemia is a well-known consequence of chronic kidney disease; its prevalence increases with the progression of renal failure and occurs in up to 95% of patients in the final stages of chronic kidney disease. In recent years, the greatest advance in the treatment of renal anemia has been made by the introduction of erythropoietin preparations, the application of which has significantly improved the patients' quality of life. The aim of this study was to analyze whether the treatment of renal anemia in chronic kidney disease patients not treated by dialysis affects the outcome of their treatment, reduces the incidence of cardiovascular diseases, delays the need of dialysis, reduces morbidity and mortality, and reduces the incidence of adverse cardiovascular events.. The study included patients with chronic kidney disease presenting for regular outpatient follow up at Department of Nephrology and Dialysis, Rijeka University Hospital Center. Patients were divided into two groups. Group 1 included patients whose renal anemia was treated with erythropoietin and group 2 patients whose anemia of chronic kidney disease was treated in any other way, regardless of the reason for the exclusion of erythropoietin. Each group included 31 patients with chronic kidney disease. During two years, each patient's laboratory parameters of chronic renal disease and renal anemia treatment were monitored at intervals not longer than six months. In addition, each patient's number of hospitalizations was recorded, taking into account the cause of hospitalization and the number of days spent in hospital.. During the two-year period, 62 patients with chronic kidney disease were analyzed (31 patients in the groups receiving and not receiving erythropoietin each). The mean age was 66 +/- 13.5 in the group receiving erythropoietin and 68 +/- 13.6 in the group not receiving erythropoietin. There were 70% of men and 30% of women in the former group, and 53% of men and 47% of women in the latter group. Examination for comorbid conditions (diabetes, hypertension, hyperlipoproteinemia and previous stroke) revealed no statistically significant differences between the two groups of patients. There were no statistically significant differences in changes of biochemical parameters (Fe, ferritin, CRP, albumin, calcium, phosphorus) between the two groups of patients during the two-year period either. There was no statistically significant between group-difference in the glomerular filtration rate after two years, but a tendency of slower progression of renal failure was observed in patients having received erythropoietin as compared to those who did not receive erythropoietin. Moreover, the number of hospitalizations due to adverse cardiovascular events was statistically significantly lower in patients that received erythropoietin, while there was no statistically significant difference in the total number of hospitalizations, hospitalizations for other indications (infection, bleeding, and worsening of renal failure), or total number of days spent in hospital, regardless of indication.. The number of patients with chronic kidney disease and those with end-stage renal failure requiring renal replacement therapy is increasing. Renal anemia, which occurs as a consequence of chronic kidney disease, is associated with increased morbidity and mortality, and with a reduced quality of life in these patients. Consequently, it is necessary to recognize this condition and apply appropriate treatment early in order to prolong life and improve the quality of life of patients with chronic kidney disease.

Topics: Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Recombinant Proteins; Renal Insufficiency, Chronic

To evaluate the safety and efficacy of epoetin alfa administered in extended-dosing intervals to a target hemoglobin (Hb) level not exceeding 12.0 g/dL for the treatment of anemia in subjects with chronic kidney disease (CKD) not on dialysis.. An open-label, randomized, multicenter, controlled study consisting of a 1-week screening phase and a 26-week open-label treatment phase.. Twenty-seven long term care (LTC) facilities in the United States.. Subjects with CKD who were not receiving dialysis, who had not received an erythropoiesis-stimulating agent for 8 weeks before screening, and whose Hb levels were lower than 11.0 g/dL at screening were eligible.. In the epoetin alfa group, subjects were administered 20,000 international units epoetin alfa subcutaneously every 2 weeks (Q2W). Dosing was based on the Hb concentration measurement obtained by HemoCue Hb201+System (Quest Diagnostics; Madison, NJ) at the time of the scheduled dose. When the Hb concentration was 11.0 to 11.5 g/dL on 2 consecutive biweekly measurements, the dose was doubled and administered on the day that the second consecutive measurement was obtained. The dosing interval was then extended to every 4 weeks (Q4W). Subjects in the standard of care (SOC) group received treatment for their anemia according to the practice of the LTC facility.. Study visits were every 2 weeks, at which time blood was drawn and used for efficacy analysis. Measurements included: the Hb concentration change from baseline to the end of the study; the proportion of subjects who achieved an Hb response (defined as 2 consecutive Hb measurements at least 1.0 g/dL greater than baseline or 2 consecutive Hb measurements ≥11.0 g/dL at any time during the study); the time to the Hb response; the proportion of subjects who received a transfusion and the number of units of transfused; the proportion of epoetin alfa-treated subjects converting to Q4W dosing; and the proportion of subjects who converted to Q4W dosing and remained on Q4W dosing through the end of the study.. A total of 157 subjects were randomized: 118 subjects to the epoetin alfa group and 39 to the SOC group. The mean change in Hb was significantly greater in the epoetin alfa group (0.9 g/dL) compared with the SOC group (0.3 g/dL) (P = .006). A significantly greater percentage of subjects achieved a Hb response in the epoetin alfa group (85.1%) compared with the SOC group (53.8%) (P < .001). The time to achieve a Hb response was significantly shorter in the epoetin alfa group (41 days) than in the SOC group (114 days) (P < .0001). There were no transfusions in the SOC group, whereas 4 subjects (3.5%) required transfusions in the epoetin alfa group. Of the 114 subjects receiving epoetin alfa, 33 (28.9%) subjects were converted to Q4W dosing, and all subjects who converted were able to be maintained on this schedule.. The administration of epoetin alfa in extended-dosing intervals of Q2W followed by Q4W was safe and effective in the treatment of anemia in subjects with CKD who reside in LTC facilities.

Topics: Aged; Aged, 80 and over; Anemia; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Long-Term Care; Male; Outcome Assessment, Health Care; Recombinant Proteins; Residential Facilities; United States

Anemia is an expected consequence of intensive chemotherapy regimens administered to patients with acute leukemia. This study was designed to determine whether epoetin alpha would decrease the number of transfusion events and units of packed erythrocytes (PRBCs) transfused, and the secondary objective was to study the effects of epoetin alpha on quality of life (QOL) and complete remission (CR) rates.. Patients with acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma (LL), or Burkitt lymphoma (BL) who were receiving frontline myelosuppressive chemotherapy were randomized to receive epoetin alpha or no epoetin during the first 6 cycles of their planned chemotherapy. QOL was assessed by using the Edmonton Symptom Assessment Scale (ESAS) and the Functional Assessment of Cancer Therapy (FACT)-Anemia questionnaires.. Fifty-five patients were randomized to receive epoetin alpha, and 54 patients received no epoetin. Transfusion data were available for 79 of 81 evaluable patients (98%) who completed the treatment/observation period. The trial was stopped early because of poor accrual before the target of 123 evaluable patients was met. A mean of 10.6 units of PRBCs over 5 months were administered to those who received epoetin alpha compared with 13 units for those who did not receive epoetin (P = .04). There was no significant difference in QOL as assessed by the FACT-Anemia or ESAS instruments. The CR rate and the 3-year CR duration were not affected adversely by use of epoetin alpha.. Epoetin alpha decreased the number of PRBC transfusions and did not appear to have a negative impact on remission duration. No difference in QOL was observed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Burkitt Lymphoma; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasm Staging; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Quality of Life; Recombinant Proteins; Remission Induction; Surveys and Questionnaires; Survival Rate; Treatment Outcome; Young Adult

Achieving a higher hemoglobin (Hb) level might allow the anemic, critically ill, trauma patient to have an improved outcome during rehabilitation therapy.. Patients with major blunt trauma orthopedic injuries were administered epoetin alfa or placebo weekly both in hospital and for up to 12 weeks after discharge or until the Hb level was >12.0 g/dL, whichever occurred first. The 36-question Short Form Health Assessment questionnaire (SF-36) was used to evaluate physical function (PF) outcomes at baseline, at hospital discharge, and at several time points posthospital discharge.. One hundred ninety-two patients were enrolled (epoetin alfa [n = 97], placebo [n = 95]). Hb increased from baseline to hospital discharge in both groups (epoetin alfa: 1.2 g/dL vs placebo: 0.9 g/dL), and transfusion requirements were similar between groups. Both groups showed improvements in SF-36 PF; there were no significant differences in the average of all posthospital discharge scores (epoetin alfa: 27.3 vs placebo 30.9; P = 0.38). Thromboembolic events were similar between groups.. No differences were observed in physical function outcomes or safety in anemic, critically ill, trauma patients treated with epoetin alfa compared with placebo.

Topics: Adult; Anemia; Critical Illness; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Injections, Subcutaneous; Injury Severity Score; Male; Prospective Studies; Recombinant Proteins; Reference Values; Risk Assessment; Survival Rate; Treatment Outcome; Wounds and Injuries; Wounds, Nonpenetrating; Young Adult

HX575 is a biosimilar version of epoetin-α that is approved for the treatment of anemia associated with chronic kidney disease (CKD) using the intravenous route of administration. Here we report data from a study of anemic pre-dialysis patients to assess the safety, immunogenicity and efficacy of subcutaneous (s.c.) administration of HX575 vs. Erypo®/Eprex® (Ortho Biotech, Neuss, Germany).. This was a randomized, double-blind study in adult patients (n = 337) with Stage III - V CKD and a hemoglobin (Hb) level of 7.5 - 11.0 g/dl. Eligible patients were randomized to 52 weeks of treatment with HX575 or Erypo®/Eprex® at a starting dose of 25 IU/kg body weight 3 times weekly or 75 IU/kg body weight once weekly during Weeks 1 - 5. This could be adjusted after 5 weeks to maintain Hb levels between 10 and 12 g/dl. The primary objective was to assess the safety and immunogenicity of HX575 compared with Erypo®/Eprex®. Efficacy endpoints were mean absolute change in Hb from baseline to end of Week 13 and mean weekly epoetin dosage in Weeks 11 - 13.. HX575 was equivalent to Erypo®/Eprex® in terms of maintaining Hb levels and epoetin dose requirements. Two patients in the HX575 group developed neutralizing antibodies (NAbs) to erythropoietin, which resulted in the study being terminated prematurely. Aside from these two events, reported adverse events were as expected for patients with Stage III - V CKD and similar in both treatment groups.. This study demonstrated the efficacy and therapeutic equivalence of s.c. HX575 compared with the reference epoetin-α, but 2 patients developed NAbs during treatment with s.c. HX575 in this study. Results of a thorough root-cause analysis reported elsewhere indicate that increased tungsten exposure in pre-filled syringes precipitated immunogenic reactions.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antibodies; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Humans; Injections, Subcutaneous; Male; Middle Aged; Recombinant Proteins; Renal Insufficiency, Chronic; Young Adult

Conflicting relationships have been described between anemia correction using erythropoiesis-stimulating agents and progression of chronic kidney disease (CKD). This study was undertaken to examine the impact of target hemoglobin level on progression of kidney disease in the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial.. Secondary analysis of a randomized controlled trial.. 1,432 participants with CKD and anemia.. Participants were randomly assigned to target hemoglobin levels of 13.5 versus 11.3 g/dL with the use of epoetin alfa.. Cox regression was used to estimate HRs for progression of CKD (a composite of doubling of creatinine level, initiation of renal replacement therapy, or death). Interactions between hemoglobin target and select baseline variables (estimated glomerular filtration rate, proteinuria, diabetes, heart failure, and smoking history) also were examined.. Participants randomly assigned to higher hemoglobin targets experienced shorter time to progression of kidney disease in both univariate (HR, 1.25; 95% CI, 1.03-1.52; P = 0.02) and multivariable models (HR, 1.22; 95% CI, 1.00-1.48; P = 0.05). These differences were attributable to higher rates of renal replacement therapy and death for participants in the high hemoglobin arm. Hemoglobin target did not interact with estimated glomerular filtration rate, proteinuria, diabetes, or heart failure (P > 0.05 for all). In the multivariable model, hemoglobin target interacted with tobacco use (P = 0.04) such that the higher target had a greater risk of CKD progression for participants who currently smoked (HR, 2.50; 95% CI, 1.23-5.09; P = 0.01), which was not present for those who did not currently smoke (HR, 1.15; 95% CI, 0.93-1.41; P = 0.2).. A post hoc analysis; thus, cause and effect cannot be determined.. These results suggest that a high hemoglobin target is associated with a greater risk of progression of CKD. This risk may be augmented by concurrent smoking. Further defining the mechanism of injury may provide insight into methods to optimize outcomes in anemia management.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Anemia; Confidence Intervals; Disease Progression; Drug Delivery Systems; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Glomerular Filtration Rate; Hematinics; Hemoglobinometry; Hemoglobins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Regression Analysis; Renal Insufficiency, Chronic; Risk Assessment; Severity of Illness Index; Survival Rate; Treatment Outcome

HX575 was approved in the European Union in August 2007 as the first-ever biosimilar epoetin-α product. The present study extended the safety database on HX575 by monitoring adverse events (AEs) in clinical practice. Hemoglobin (Hb) levels and HX575 doses were recorded for the assessment of efficacy. This open, 6-month single-arm study was conducted in 10 European countries with a target enrollment of 1,500 patients with anemia due to chronic kidney disease (CKD). HX575 was intravenously (i.v.) administered aiming at an Hb target of 10 - 12 g/dl. Most patients (92.3%) had already received erythropoiesis stimulating agents (ESAs) treatment before enrolment into this study; the recorded treatments mainly comprised i.v. or subcutaneous (s.c.) administration of epoetin-α, epoetin-β or darbepoetin. The study period covered 770 patient years. The observed AE profile was in line with expectations for this patient population. Thrombotic vascular events (TVEs) were reported in 11.9% of patients (0.2612 per patient year). Tumor incidence was 1.4% (0.0299 per patient year). No subject developed anti-epoetin antibodies. Mean Hb levels were effectively maintained between 11.2 and 11.3 g/dl following the conversion from a broad spectrum of pre-study ESA treatments with stable overall mean i.v. HX575 doses. The proportion of patients within the Hb target range increased from 57.5% at baseline to 66.8% at study end.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Biomarkers; Biosimilar Pharmaceuticals; Chronic Disease; Epoetin Alfa; Erythropoietin; Europe; Female; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Kidney Diseases; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins; Thrombosis; Time Factors; Treatment Outcome; Young Adult

To compare usual care with a home-based individualized exercise program (HBIEP) in patients receiving intensive treatment for multiple myeloma (MM)and epoetin alfa therapy.. Randomized trial with repeated measures of two groups (one experimental and one control) and an approximate 15-week experimental period.. Outpatient setting of the Myeloma Institute for Research and Therapy at the Rockfellow Cancer Center at the University of Arkansas for Medical Sciences.. 187 patients with newly diagnosed MM enrolled in a separate study evaluating effectiveness of the Total Therapy regimen, with or without thalidomide.. Measurements included the Profile of Mood States fatigue scale, Functional Assessment of Cancer Therapy-Fatigue, ActiGraph® recordings, 6-Minute Walk Test, and hemoglobin levels at baseline and before and after stem cell collection. Descriptive statistics were used to compare demographics and treatment effects, and repeated measures analysis of variance was used to determine effects of HBIEP.. Fatigue, nighttime sleep, performance (aerobic capacity) as dependent or outcome measures, and HBIEP combining strength building and aerobic exercise as the independent variable.. Both groups were equivalent for age, gender, race, receipt of thalidomide, hemoglobin levels, and type of treatment regimen for MM. No statistically significant differences existed among the experimental and control groups for fatigue, sleep, or performance (aerobic capacity). Statistically significant differences (p < 0.05) were found in each of the study outcomes for all patients as treatment progressed and patients experienced more fatigue and poorer nighttime sleep and performance (aerobic capacity).. The effect of exercise seemed to be minimal on decreasing fatigue, improving sleep, and improving performance (aerobic capacity).. Exercise is safe and has physiologic benefits for patients undergoing MM treatment; exercise combined with epoetin alfa helped alleviate anemia.

Topics: Adult; Affect; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Exercise; Fatigue; Female; Home Care Services; Humans; Male; Middle Aged; Models, Biological; Motor Activity; Multiple Myeloma; Muscular Atrophy; Peripheral Blood Stem Cell Transplantation; Polysomnography; Recombinant Proteins; Resistance Training; Sleep Disorders, Intrinsic; Thalidomide; Walking

Chemotherapy-induced anemia is a frequent complication in cancer treatment. The aim was to develop a pharmacokinetic (PK) model that describes the time-dependent decline of epoetin alfa (rHuEPO) clearance following thrice (t.i.w.) or once (q.w.) weekly subcutaneous injections in cancer patients using a population PK approach. Serum concentrations of rHuEPO were available retrospectively from a phase I study. A one-compartment model with first-order elimination described rHuEPO PK. Sequential zero- and first-order (k(a)) processes with duration (t(lag)) characterized the absorption. Population PK analysis was performed using NONMEM. The influence of several covariates was tested. Model evaluation was performed using visual predictive check. Precision of parameter estimates was assessed by standard errors and confidence intervals determined by bootstrap analysis. Apparent clearance (CL/F) and volume of distribution (V(c)/F) were 25.6% lower and 29.2% higher for q.w. than t.i.w. groups. RHuEPO was absorbed for 10% during 24.6 h through the zero-order process. Following which 90% of the dose was absorbed through the first-order process with k(a) of 0.033 h⁻¹. The most significant covariates were the time-dependent decrease of CL/F with an increase in body weight, a decrease in reticulocyte count, a decrease in hemoglobin baseline, an increase in total number of chemotherapy cycles, and platinum-containing chemotherapy. AGE served as an important covariate on FRAC and k(a). Visual predictive check showed no deviation from observed values. The PK model adequately predicted rHuEPO concentration-profiles in all individuals. Relevant covariates were identified and incorporated into the model.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Models, Biological; Neoplasms; Nonlinear Dynamics; Recombinant Proteins; Retrospective Studies; Time Factors; Tissue Distribution

The aim of this study was to analyze the prevalence and efficacy of renal anemia treated with epoetin in maintenance kidney transplant recipients in Slovenia. By the end of 2009, 107 out of 537 patients (19.9%) had been treated with epoetin. A cohort of 49 patients (45.8%) were analyzed in detail: 11 patients received epoetin alpha, 18 epoetin beta, 10 darbepoetin alpha, and 10 patients received methoxy polyethylene glycol-epoetin beta. The median epoetin dose was 0.36 µg/kg body weight per week. The median serum laboratory parameters were as follows: hemoglobin 120 g/L, hematocrit 0.36, ferritin 332 ng/mL, transferrin saturation 34%, serum creatinine 145 µmol/L, serum albumin 41 g/L, intact parathyroid hormone 79 ng/L, and C-reactive protein 3 mg/L. We concluded that the prevalence of renal anemia in kidney transplant recipients treated with epoetin was approximately 20%, and laboratory parameters suggested that the treatment of renal anemia in this study cohort was optimal.

Topics: Adult; Aged; Anemia; Cohort Studies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Transplantation; Male; Middle Aged; Polyethylene Glycols; Prevalence; Recombinant Proteins; Slovenia; Young Adult

Topics: Anemia; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoietin; Humans; Recombinant Proteins; Therapeutic Equivalency

The CHOIR trial in anemic patients with chronic kidney disease compared epoetin-alfa treatment with low (11.3 g/l) and high (13.5 g/l) hemoglobin targets on the composite end point of death, hospitalization for heart failure, stroke, and myocardial infarction. However, other anemia management trials in patients with chronic kidney disease found there was increased risk when hemoglobin is targeted above 13 g/dl. In this secondary analysis of the CHOIR trial, we compared outcomes among the subgroups of patients with diabetes and heart failure to describe the comparative relationship of treatment to these two different hemoglobin goals. By Cox regression analysis, there was no increased risk associated with the higher hemoglobin target among patients with heart failure. In patients without heart failure, however, the hazard ratio (1.86) associated with the higher target was significant. Comparing survival curves in an unadjusted model, patients with diabetes did not have a greater hazard associated with the higher target. Subjects without diabetes had a significantly greater hazard in the high as compared to the low target, but the interaction between diabetes and the target was not significant. We suggest that the increased risks associated with higher hemoglobin targets are not clinically apparent among subgroups with greater mortality risk. These differential outcomes underscore the need for dedicated trials in these subpopulations.

Topics: Aged; Aged, 80 and over; Anemia; Chronic Disease; Comorbidity; Diabetes Mellitus; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Regression Analysis; Retrospective Studies; Survival Analysis; Treatment Outcome

Anaemia during chemotherapy is often left untreated. Erythropoiesis-stimulating agents are frequently used to treat overt anaemia. Their prophylactic use, however, remains controversial and raises concerns about cost-effectiveness. Therefore, we assessed the efficacy of a dose-reduction schedule in anaemia prophylaxis.. The study included patients with untreated solid tumours about to receive platinum-based chemotherapy and had haemoglobin (Hb) levels ≥11 g/dL. Epoetin-α was administered at a dose level of 3 × 10,000 U weekly as soon as Hb descended to < 13 g/dL. Dose reductions to 3 × 4,000 U and 3 × 2,000 U weekly were planned in 4-week intervals if Hb stabilised in the range of 11-13 g/dL. Upon ascending to ≥13 g/dL, epoetin was discontinued. Iron supplements of 100 mg intravenous doses were given weekly. Of 37 patients who enrolled, 33 could be evaluated.. Their median Hb level was 13.7 (10.9-16.2) g/dL at baseline and descended to 11.0 (7.4-13.8) g/dL by the end of chemotherapy. Anaemia (Hb < 10 g/dL) was prevented in 24 patients (73%). The mean dose requirement for epoetin-α was 3 × 5,866 U per week per patient, representing a dose reduction of 41%. Treatment failed in nine patients (27%), in part due to epoetin-α resistance in four (12%) and blood transfusion in three (9%) patients.. Dose reduction was as effective as fixed doses in anaemia prophylaxis but reduced the amount of prescribed epoetin substantially.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins

Extended-interval dosing of epoetin alfa (EPO) is commonly used to treat anemia in patients with chronic kidney disease (CKD). This study aimed to demonstrate that EPO dosed every 2 weeks (Q2W) and every 4 weeks (Q4W) was noninferior to once-weekly (QW) dosing.. 430 anemic subjects with stage 3 to 4 CKD receiving a stable QW dose of EPO were randomized 1:1:2 to QW, Q2W, and Q4W dosing for 36 weeks. Hemoglobin (Hb) was measured weekly, and the dose of EPO was adjusted to maintain an Hb level of 11.0 to 11.9 g/dl. The primary endpoint was change in Hb from baseline to the average of the last 12 weeks of treatment.. Both the Q2W and Q4W dosing groups were noninferior to the QW group. The estimated difference of the mean change in Hb between Q2W and QW was -0.03 g/dl; and between Q4W and QW was -0.09 g/dl. From weeks 13 to 37, the mean percentage of weeks per subject with Hb 10.0 to 11.9 g/dl, inclusive, was 81% for QW, 81% for Q2W, and 75% for Q4W. Death occurred, respectively, in 4%, 3%, and 4%; thromboembolic vascular events occurred in 3%, 5%, and 3%; and serious adverse events occurred in 22%, 26%, and 26% of subjects.. Q2W and Q4W EPO dosing maintained Hb levels in subjects with stage 3 to 4 CKD. Deaths, thromboembolic vascular events, and serious adverse events were comparable across the dosing groups.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Drug Administration Schedule; Drug Monitoring; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Iron Compounds; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Risk Assessment; Severity of Illness Index; Thromboembolism; Time Factors; Treatment Outcome; United States; Young Adult

To determine whether epoetin alfa reduces anemia-related fatigue, improves other aspects of health-related patient-recorded outcomes (PROs), reduces the number of RBC transfusions, and has an impact on freedom from treatment failure (FFTF) and overall survival (OS) in patients with advanced-stage Hodgkin's lymphoma (HL).. The prospectively randomized HD15EPO study performed by the German Hodgkin Study Group investigated epoetin alfa administered at doses of 40,000 U weekly during and after chemotherapy (six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPP]) in a double-blind, placebo-controlled setting. The study accrued 1,379 patients, of whom 1,328 were assessable for safety, 1,303 were assessable for clinical outcome, and 930 were assessable for PROs.. PROs were not different in patients receiving placebo or epoetin alfa, both after the end of chemotherapy and 6 months thereafter. There was no difference between patients treated with epoetin alfa or placebo with respect to FFTF and OS. There were also no differences in the numbers of deaths, progressions, relapses, and thromboembolic events. The median number of RBC transfusions was reduced from four per patient in the placebo group to two per patient in the epoetin alfa group (P < .001), with 27.4% of patients needing no RBC transfusion in the placebo group compared with 36.7% of patients in the epoetin alfa group (P < .001).. Epoetin alfa administered at 40,000 U weekly parallel to BEACOPP chemotherapy was safe in patients with advanced-stage HL and reduced the number of RBC transfusions but had no impact on fatigue and other PRO domains.

Topics: Adolescent; Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Double-Blind Method; Doxorubicin; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Etoposide; Fatigue; Female; Germany; Hematinics; Hodgkin Disease; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Staging; Prednisone; Procarbazine; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vincristine; Young Adult

The primary objective of the trial was to prove the therapeutic equivalence of epoetin zeta to epoetin alfa when administered subcutaneously for maintaining target hemoglobin (Hb) in patients with renal anemia on chronic hemodialysis. Additional information was provided on the safety and tolerability of epoetin zeta with particular focus on the formation of anti-erythropoietin antibodies.. A total of 462 patients were randomized to either epoetin zeta or alfa for 28 weeks after an open period of dose adjustment of 12-16 weeks with only epoetin zeta. The aim of treatment was to maintain Hb between 10.0-12.0 g/dL with constant epoetin dosage. Primary endpoints were the mean Hb level and the mean weekly epoetin dosage during the last 4 weeks of treatment. Safety endpoints were the occurrence of anti-erythropoietin antibodies, incidence of Hb levels above 13 g/dL, ratings of tolerability, and adverse events (AEs).. The mean Hb level (+/-SD) during the last 4 weeks of treatment was 10.94+/-0.84 g/dL (epoetin zeta) and 11.02+/-0.94 g/dL (epoetin alfa). The 95% confidence interval (CI) (''C0.28 g/dL to 0.12 g/dL) was entirely within the predefined equivalence range (+/-0.5 g/dL). The mean weekly epoetin dosage per body weight over the last 4 weeks of treatment was 97.0+/-94.3 IU/kg/week (epoetin zeta) and 86.0+/-78.0 IU/kg/week (epoetin alfa). The 95% CI (''C8.06 IU/kg/week to 29.96 IU/kg/week) was also within the predefined equivalence range of +/-45 IU/kg/week. The most common AEs were infections and infestations (15.1% of patients on epoetin zeta and 14.8% of patients on epoetin alfa). None of the patients developed anti-erythropoietin antibodies.. Epoetin zeta, administered subcutaneously, is equivalent to epoetin alfa in respect of its clinical efficacy. The safety profile of both products is similar: no unexpected AEs were observed, no patients developed anti-erythropoietin antibodies, and both epoetin preparations were well tolerated.

Topics: Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Single-Blind Method; Therapeutic Equivalency

Anemia is an early sign of chronic kidney dysfunction, caused by many different factors, but the insufficient erythropoietin synthesis is the crucial factor in its development.. The objective of our study was to compare effectiveness of epoietin alpha and beta application in the treatment of renal anemia in chronic hemodialyzed patients.. The group included 60 patients of both sexes, randomly chosen. Criteria for including patients into the study were: older than 18 years, haemodialyzed longer than three months and treated by epoietin beta, stable level of hemoglobin, between 9 and 11 g/dL at least two successive measurements and no malignant disease present. The patients were then randomized into groups: 20 patients were administered epoietin alpha intravenously instead of epoietin beta subcutaneously (experimental group); 20 patients were administered intravenously epoietin beta instead of epoietin beta subcutaneously (control group A), the rest of 20 patients were administered epoietin beta subcutaneously (control group B). All the testees were administered epoietin alpha or beta three times weekly after haemodialysis, intravenously or subcutaneously.. Comparison among mean values of hematological and biochemical parameters before starting the treatment by erythropoietin, and third and sixth months after therapy in the studied groups, no significant difference was found (p > 0.05).. Epoietin alpha and beta showed approximate degree of efficacy in renal anemia treatment of hemodialysis patients. The way of erythropoetin administration did not significantly effect the level of hemoglobin and hematocrit in six months research period.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Anemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are commonly used to increase hemoglobin levels in this population. In observational studies, higher hemoglobin levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to hemoglobin levels around 9-10 g/dL. A systematic review of randomized trials found that targeting higher hemoglobin levels with ESA causes an increased risk of adverse vascular outcomes. It is possible, but has never been formally tested in a randomized trial, that ESA dose rather than targeted hemoglobin concentration itself mediates the increased risk of adverse vascular outcomes. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) trial will assess the benefits and harms of a high versus a low fixed ESA dose for the management of anemia in patients with end stage kidney disease.. This is a randomized, prospective open label blinded end-point (PROBE) trial due to enrol 2204 hemodialysis patients in Italy. Patients will be randomized 1:1 to 4000 IU/week versus 18000 IU/week of intravenous epoietin alfa or beta, or any other ESA in equivalent doses. The dose will be adjusted only if hemoglobin levels fall outside the 9.5-12.5 g/dL range. The primary outcome will be a composite of all-cause mortality, non fatal stroke, non fatal myocardial infarction and hospitalization for cardiovascular causes. Quality of life and costs will also be assessed.. The C.E.DOSE study will help inform the optimal therapeutic strategy for the management of anemia of hemodialysis patients, improving clinical outcomes, quality of life and costs, by ascertaining the potential benefits and harms of different fixed ESA doses.. Clinicaltrials.gov NCT00827021.

Topics: Adult; Anemia; Cardiovascular Diseases; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Female; Health Care Costs; Hematinics; Hemoglobins; Hospitalization; Humans; Kidney Failure, Chronic; Male; Outcome Assessment, Health Care; Quality of Life; Recombinant Proteins; Renal Dialysis

To evaluate the effects of epoetin alfa on patient-reported outcomes (PROs) in patients with breast cancer receiving myelotoxic chemotherapy.. Women with hemoglobin concentrations ≤ 12.0 g/dl and an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-3 were randomized 1:1 to receive epoetin alfa (10,000 IU 3 times weekly) or best standard care (BSC) during chemotherapy. The primary endpoint was the change from baseline in the total anemia subscale assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaire after 12 weeks of treatment. The fatigue and nonfatigue subscales from the FACT-An, the Cancer Linear Analog Scale (CLAS), hemoglobin changes, ECOG PS score, tumor response, overall survival, and safety also were evaluated.. Of 223 patients randomized, 216 constituted the modified intent-to-treat population. Percentage changes in the total anemia subscale of the FACT-An were significantly different between epoetin alfa treatment (14.2%) and BSC (-0.5%; p = .002), favoring epoetin alfa; so were changes in the FACT-An fatigue subscale (epoetin alfa, 17.5%; BSC, -0.9%; p = .003) and nonfatigue subscale (epoetin alfa, 8.8%; BSC, 0.2%; p = .008). Similar results were observed with the CLAS. Hemoglobin concentrations > 12 g/dl were more common with epoetin alfa (62.0%) than with BSC (27.6%). Tumor response, ECOG PS score, 12-month survival rate, and the incidence of serious treatment-emergent adverse events were similar between groups.. Early intervention with epoetin alfa was well tolerated and improved anemia-related PROs in patients with breast cancer receiving myelotoxic chemotherapy.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Middle Aged; Prospective Studies; Recombinant Proteins

Treatment of anaemia in renal-insufficient patients relies on the use of an erythropoiesis-stimulating agent (ESA). This study aimed to compare the impact of two different strategies of ESA prescribing on variation in haemoglobin (Hb) concentration in end-stage renal disease (ESRD) patients.. Patients with ESRD, on haemodialysis, and who had received ESA for >3 months were recruited. Different parameters were analysed: demographics, Hb level the last day of the year before dialysis, the most recent weekly ESA dose, risk factors for resistance and cost. Each institution continued its local practice for achieving the desired Hb level: increasing the ESA dose to overcome resistance in one centre and defining an upper ESA-dose limit in the other.. A total of 185 patients were recruited. No significant differences in the biological parameters were found between the two populations. In both centres, Hb levels were comparable and mean levels exceeded 11 g/dL, despite the higher ESA doses given in one centre to achieve this target. This finding also held true for the subgroups with greater than or equal to two resistance factors. These two strategies led to large between-centre differences in treatment costs.. The ESA-use strategy difference probably indicates that erythropoietin-resistance was not overcome with increased dosing. The Hb concentrations remained stable even when ESA doses were increased. On current evidence, the cheaper ESA-dose limitation strategy is preferable but randomized controlled studies, including comparisons of alternative ESA formulations are necessary.

Topics: Aged; Anemia; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; France; Hematinics; Humans; Inpatients; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Treatment Outcome

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Anemia; Castration; Double-Blind Method; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Recombinant Proteins; Venous Thromboembolism

Epoetin-alpha initiated once weekly, followed by once-every-3-weeks maintenance, was effective and well tolerated for chemotherapy-induced anemia. This study evaluated a starting dose of epoetin-alpha 120,000 U once every 3 weeks for chemotherapy-induced anemia using early and late initiation regimens.. Patients with baseline hemoglobin 11.0-12.0 g/dL were randomly assigned to early intervention with immediate epoetin-alpha (n = 68) or to standard intervention with epoetin-alpha when hemoglobin decreased to <11 g/dL (n = 68). A third group of patients with baseline hemoglobin <11 g/dL (n = 50) were enrolled but not randomized; epoetin-alpha was initiated immediately. The primary endpoint was mean proportion of hemoglobin values within the target range (11.0-13.0 g/dL) among randomized patients.. The mean proportion of hemoglobin values in range through week 16 was 60% in each randomized group. Mean hemoglobin by week showed similar increases over the study. Blood transfusions were administered in 9%, 8%, and 24% of patients in the early, standard, and nonrandomized groups. Mean epoetin-alpha doses were similar between treatment groups. Dose reductions and withholds were more common in the early intervention group. Adverse events (eg, diarrhea, fatigue, nausea) were consistent with the safety profile for epoetin-alpha . Clinically relevant thrombotic vascular events (regardless of relationship to study treatment) were reported for 9%, 12%, and 12% of patients in the early, standard, and nonrandomized groups.. Early and standard intervention with epoetin-alpha, administered once every 3 weeks, increased and maintained hemoglobin levels within 11.0-13.0 g/dL in patients with chemotherapy-induced anemia.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins

Epoetin (EPO) administration reduces the need for transfusion. Identifying patients at high risk of anemia requiring red blood cell (RBC) transfusion is needed. This multicentric phase III trial tested epoetin alpha (EPOalpha) administration according to our risk model on the basis of three clinical parameters: hemoglobin (Hb) <12 g/dl, lymphocytes 1.. Patients >or=18 years with chemotherapy-treated solid or hematologic tumors were randomized to 150 UI/kg/TIW s.c. EPOalpha (arm 1) or no EPOalpha (arm 2) and stratified on Hb level at day 0, lymphocyte count, and PS. The primary end point was transfusion rate; secondary end points included overall survival (OS), safety, and quality of life.. From September 2000 to January 2005, 218 patients (median age 64 years, 42.7% males) with principally breast cancer, sarcoma, or lung carcinoma were included. In total, 93% patients had PS >1 and 35% had

Topics: Adult; Aged; Aged, 80 and over; Anemia; Chemoprevention; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Models, Biological; Neoplasms; Prospective Studies; Recombinant Proteins; Risk Factors

This prospective study quantifies the response of hemoglobin and other blood factors to Epoetin alpha (EPO) administration in the course of pre-operative chemotherapy in breast cancer. Blood count time series were analyzed in 38 primary breast cancer patients with/without EPO during the course of pre-operative chemotherapy with epirubicin and paclitaxel. EPO injections improved blood counts in 'anemic' patients (< or =12.0 g/dl) receiving chemotherapy, but had little effect when administered to patients with higher hemoglobin concentrations. On the average, without chemotherapy, hemoglobin concentrations drifted toward about 11.1 g/dl without EPO but could be maintained at near 12.0 g/dl with EPO. In conclusion, there is potential for improved anemia management using EPO during pre-operative chemotherapy, which not only benefits quality of life but could also influence long-term survival in breast cancer through improved tumor oxygenation.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Epirubicin; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Middle Aged; Neoadjuvant Therapy; Paclitaxel; Recombinant Proteins

To describe the pharmacokinetic profiles of six different dosing regimens for epoetin alfa, and whether more rapid and robust reticulocytosis can be elicited with more frequent administration of epoetin alfa in anemic critically ill patients.. Randomized, open-label, multicenter, 28-day clinical trial.. Ten centers in the United States.. Adult (age >or=18 years) critically ill patients with hemoglobin or=7 days, with no ongoing acute blood loss.. One of six dosing epoetin alfa regimens for 15 days, as follows: 40,000 IU once weekly, subcutaneously (group A) or intravenously (IV) (group B); 15,000 IU every other day, subcutaneously (group C) or IV (group D); or 40,000 IU day 1 and 3, subcutaneously (group E) or IV (group F), followed by 15,000 IU once every other day on [corrected] days 5-15 [corrected]. Serum erythropoietin concentration, absolute reticulocyte count, and adverse events.. Of the 60 patients who were enrolled (60% men, mean age 53 years, mean Acute Physiology and Chronic Health Evaluation II score, 19.5), 30 were evaluable for both pharmacokinetics and pharmacodynamics (50%). Erythropoietin exposure was approximately ten times greater for IV dosing than for subcutaneous dosing. Mean absolute reticulocyte count peaked at day 11 or 15 in each group and appeared to be greater for subcutaneous dosing (mean peak response 149-169 x 10(9)/L) compared with IV dosing (mean peak response 138-147 x 10(9)/L) at most visits. The most frequently reported adverse events were pyrexia (18%), hypokalemia (15%), and hypophosphatemia (15%).. In this study of anemic critically ill patients treated with epoetin alfa, all dosing regimens were well tolerated and appeared to effect reticulocytosis, with a peak at day 11 or 15 in most patients. The pharmacokinetics of epoetin alfa did not predict pharmacodynamic response in anemic critically ill patients.

Topics: Adult; Anemia; Critical Illness; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Recombinant Proteins

Erythropoietin corrects and prevents anemia and decreases the need for red blood cell (RBC) transfusions; its impact on quality of life (QOL) of cancer patients receiving chemotherapy is not clear.. 399 patients with solid tumors and Hb level of < or = 12 g/dl receiving chemotherapy were randomized to receive or not 10,000 IU epoetin-alpha thrice weekly. QOL was measured by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale and various subscales at baseline, at two months and at the end of the study.. Changes in the average QOL scores were similar in the two groups. The improvement in Hb levels was significantly higher for the epoetin-alpha group, with a decrease in transfusion requirements compared to the control group.. Epoetin-alpha does not improve QOL of patients with solid tumors receiving chemotherapy as assessed using FACT-An scale and various subscales, despite improving Hb levels and reducing transfusion requirements.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Organoplatinum Compounds; Quality of Life; Recombinant Proteins; Treatment Outcome; Young Adult

The effects of different hemoglobin targets when using erythropoiesis-stimulating agents on quality of life are somewhat controversial, and predictors of change in quality of life in endstage renal disease have not been well characterized.. Five hundred ninety-six incident hemodialysis patients without symptomatic cardiac disease were randomly assigned to hemoglobin targets of 9.5 to 11.5 g/dl or 13.5 to 14.5 g/dl for 96 weeks, using epoetin_alfa as primary therapy. Patients and attending physicians were masked to treatment assignment. Quality of life, a secondary outcome, was prospectively recorded using the Kidney Disease Quality of Life (KDQoL) questionnaire at weeks 0, 24, 36, 48, 60, 72, 84, and 96, with prespecified outcomes being fatigue and quality of social interaction.. The mean age and prior duration of dialysis therapy of the study population were 50.8 and 0.8 yr. Mortality was low, reflecting the relatively healthy group enrolled. Of 20 domains within the KDQoL only the prespecified domain of fatigue showed significant change over time between the two groups. Improvement in fatigue scores in the high-target group ranged from 3.2 to 7.9 over time (P = 0.007) compared with change in the low-target group. Higher body mass index and lower erythropoietin dose at baseline were independent predictors of improvement in multiple KDQoL domains.. In relatively healthy hemodialysis patients, normal hemoglobin targets may have beneficial effects on fatigue. Improvement in multiple domains of quality of life is associated with higher body mass index and lower erythropoietin requirements.

Topics: Anemia; Body Mass Index; Canada; Epoetin Alfa; Erythropoietin; Europe; Fatigue; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Quality of Life; Recombinant Proteins; Renal Dialysis; Social Behavior; Surveys and Questionnaires; Time Factors; Treatment Outcome

Recombinant human epoetin alfa, HX575, is the first biosimilar erythropoiesis-stimulating agent (ESA) with European marketing authorisation. The primary objective of this double-blind, randomised, multicentre study was to assess the efficacy and safety of HX575 in treating chemotherapy-associated symptomatic anaemia in patients with solid tumours.. The patients (n = 114) were treated with HX575 or active control (epoetin alfa) at 150 IU/kg body weight 3 times weekly for 12 weeks, increased to 300 IU/kg body weight 3 times weekly if the haemoglobin/reticulocyte increase was insufficient after 4 or 8 weeks.. With HX575, haemoglobin increased by > or =20 g/l in 62% (37/60 patients). The confidence interval (48.2%, 73.9%) was entirely above the pre-defined 30% threshold. Both groups showed similar results for safety profiles and secondary efficacy parameters. Transfusion requirements were 32% (19/60) (HX575) and 38% (13/34) (epoetin alfa).. In treating chemotherapy-associated symptomatic anaemia in patients with solid tumours, the biosimilar ESA, HX575, is efficacious with a safety profile as expected for the therapeutic area.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Germany; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Single-Blind Method; Treatment Outcome

HX575 is a human recombinant epoetin alfa that was approved for use in Europe in 2007 under the European Medicines Agency biosimilar approval pathway. Therefore, in order to demonstrate the bioequivalence of HX575 to an existing epoetin alfa, the pharmacokinetic and pharmacodynamic response to steady state circulating concentrations of HX575 and a comparator epoetin alfa were compared following multiple intravenous administrations.. An open, randomised, parallel group study was conducted in 80 healthy adult males. Subjects were randomised to multiple intravenous doses of 100 IU/kg body weight of HX575 or of the comparator epoetin alfa three-times-weekly for four weeks. Serum epoetin concentrations were measured using an enzyme-linked immunosorbent assay and pharmacokinetic parameters for the two treatments were compared. The time course and area under the effect curve ratio of haematological characteristics were used as surrogate parameters for efficacy evaluation.. The haematological profiles of both treatments were similar, as determined from their population mean curves and the AUECHb ratio and 90% confidence interval (99.9% [98.5-101.2%]), the primary pharmacodynamic endpoint of this study. The pharmacokinetic parameters after the treatments showed minor differences after single dosing, but not at steady state doses. After multiple doses, HX575 was bioequivalent to the comparator with respect to the rate and extent of exposure of exogenous epoetin (AUCtau ratio and 90% confidence interval: 89.2% [82.5-96.2%]). Study medication was well tolerated with no clinically relevant differences between safety profiles of the treatments. Anti-epoetin antibodies were not detected.. HX575 and the comparator epoetin alfa were bioequivalent at steady state circulating drug concentrations with respect to their pharmacokinetic profile and pharmacodynamic action. This supports the conclusion that HX575 and the comparator epoetin alfa, when administered intraveneously, will be equally efficacious and may be interchangeable as therapy.

Topics: Adult; Anemia; Area Under Curve; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Epoetin Alfa; Erythrocyte Count; Erythropoietin; Hematinics; Hematologic Tests; Humans; Infusions, Intravenous; LEOPARD Syndrome; Male; Metabolic Clearance Rate; Recombinant Proteins; Therapeutic Equivalency; Treatment Outcome

Topics: Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Multiple Myeloma; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

PDpoietin is a recombinant erythropoietin alfa that has been introduced by a manufacturer in Iran. We assessed the effectiveness and complications of PDpoietin in comparison with Eprex in anemic patients on hemodialysis.. This clinical trial was performed in a multicenter setting. Patients with a hemoglobin level less than 12 g/dL were assigned into 2 groups in order to receive either Eprex (Janssen Cilag) or PDpoietin (Pooyesh Darou) for 3 months.. Forty-one and 34 patients completed the study in the PDpoietin and Eprex groups, respectively. The mean hemoglobin levels at baseline were not significantly different between the two groups of patients with PDpoietin and Eprex. In both groups, hemoglobin levels increased significantly, but there were no significant differences between the two groups at months 1, 2, and 3. At the end of the study, the mean hemoglobin levels reached 11.6 +/- 1.7 g/dL and 11.8 +/- 1.9 g/dL, respectively (P = .002; P = .01). The mean hemoglobin per cumulative of drug dose index (hemoglobin/[erythropoietin dose/1000 x injections per month]) was not significantly different between the two groups at different treatment stages, and it did not change significantly in each group during the course of the study. No serious complications were reported.. Eprex and PDpoietin could equally increase the hemoglobin levels with no significant complication. Therefore, PD can be used for treatment of anemia in patients on dialysis, and the patients will have the advantages of its availability and low price.

Topics: Adult; Aged; Anemia; Cost-Benefit Analysis; Drug Costs; Epoetin Alfa; Erythropoietin; Feeding Behavior; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

In clinical practice, physicians often use once-weekly (QW) and biweekly (Q2W) dosing of epoetin alfa to treat anemia in patients with chronic kidney disease (CKD). Although the literature supports this practice, previous studies were limited by short treatment duration, lack of randomization, or absence of the approved three times per week (TIW) dosing arm. This randomized trial evaluated extended dosing regimens of epoetin alfa, comparing QW and Q2W to TIW dosing in anemic CKD subjects. The primary objective was to show that treatment with epoetin alfa at QW and Q2W intervals was not inferior to TIW dosing.. 375 subjects with stage 3 to 4 CKD were randomized equally to the three groups and treated for 44 wk; to explore the impact of changing from TIW to QW administration on hemoglobin (Hb) control and adverse events, subjects on TIW switched to QW after 22 wk. The Hb was measured weekly, and the dose of epoetin alfa was adjusted to achieve and maintain an Hb level of 11.0 to 11.9 g/dl.. Both the QW and Q2W regimens met the primary efficacy endpoint. More subjects in the TIW group than in the QW and Q2W groups exceeded the Hb ceiling. Adverse events were similar across treatment groups and consistent with the morbidities of CKD patients.. Administration of epoetin alfa at QW and Q2W intervals are potential alternatives to TIW dosing for the treatment of anemia in stage 3 to 4 CKD subjects.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Hypertension, Renal; Incidence; Iron; Kidney Failure, Chronic; Male; Middle Aged; Morbidity; Recombinant Proteins; Renal Dialysis; Thromboembolism; Treatment Outcome

The recombinant human epoetin-a HX575 (Sandoz Pharmaceuticals GmbH/Hexal AG, Holzkirchen, Germany) is the first biosimilar erythropoiesis-stimulating agent (ESA) with marketing authorization in Europe. The primary objective of the study was the evaluation of therapeutic equivalence in terms of hemoglobin (Hb) response of HX575 compared with the comparator product (EPREX/ ERYPO, Janssen-Cilag/Ortho Biotech, Neuss, Germany) in the long-term intravenous (i.v.) treatment of anemia in chronic renal failure patients on hemodialysis following a 1 : 1 dose conversion from the comparator product to HX575.. Hemodialysis patients with Hb levels of 10.0 - 13.0 g/dl were randomized to either continue their current i.v. epoetin-a treatment or switch to HX575. During treatment, epoetin dosages were titrated to maintain Hb values. The primary endpoint was the difference between treatment groups in the mean absolute change of Hb levels between baseline and evaluation period (Weeks 25 - 28).. Therapeutic equivalence of HX575 and the comparator epoetin-alpha, assessed during the evaluation period, was statistically confirmed: mean changes in Hb levels were 0.15 +/- 0.09 g/dl in the HX575 and 0.06 +/- 0.12 g/dl in the comparator epoetin-a group, with a difference between groups of 0.08 g/dl (95% confidence interval: -0.17; 0.34). Hb levels and epoetin dosages remained stable throughout the entire study period of 56 weeks. The long-term safety profile of HX575 was similar to that of the comparator epoetin-alpha. No antibody formation was detected.. The study demonstrated therapeutic equivalence of biosimilar HX575 to the comparator epoetin-a, together with a comparable safety profile.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Therapeutic Equivalency; Young Adult

To evaluate the effect of epoetin alfa on local disease-free survival (DFS), overall survival (OS), and cancer treatment-related anemia and fatigue in patients with head and neck cancer receiving radical radiotherapy with curative intent.. Patients (N = 301) with hemoglobin (Hb) less than 15 g/dL were randomly assigned in a ratio of 1:1 to receive radiotherapy plus epoetin alfa (10,000 U subcutaneously [SC] three times weekly if baseline Hb was < 12.5 g/dL; 4,000 U SC three times weekly if baseline Hb > or = 12.5 g/dL) or radiotherapy alone. Hb levels were monitored weekly. The primary end point was local DFS, defined as the time from random assignment to local disease recurrence or death. Secondary efficacy end points included OS, local tumor response, and local tumor control. Patients were followed at 1, 4, 8, and 12 weeks postradiotherapy and annually for 5 years. Cancer treatment-related anemia and fatigue were evaluated with the Functional Assessment of Cancer Therapy-Anemia and Functional Assessment of Cancer Therapy-Head and Neck. Adverse events were recorded up to 12 weeks postradiotherapy.. Hb levels increased from baseline with epoetin alfa. The median duration of local DFS was not statistically different between groups (observation, 35.42 months; epoetin alfa, 31.47 months; hazard ratio, 1.04; 95% CI, 0.77 to 1.41). Groups did not significantly differ in DFS, OS, tumor outcomes, or cancer treatment-related anemia or fatigue. No new or unexpected adverse events were observed.. Addition of epoetin alfa to radical radiotherapy did not affect survival, tumor outcomes, anemia, or fatigue positively or negatively in patients with head and neck cancer.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Carcinoma, Squamous Cell; Disease Progression; Disease-Free Survival; Epoetin Alfa; Erythropoietin; Fatigue; Female; Head and Neck Neoplasms; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Recombinant Proteins; Survival Rate

Inflammatory cytokines are important predictors of cardiovascular mortality especially in patients with chronic kidney disease. Here we explored the relationship of anemia and epoetin treatment to inflammatory cytokine levels in patients with chronic kidney disease. One hundred non-dialysis patients with chronic kidney disease over 18 years of age were evenly split into anemic and non-anemic cohorts. Of the 50 anemic patients, 23 were receiving erythropoiesis stimulating agents treatments. Levels of tumor necrosis factor (TNF)-alpha were found to be significantly higher and serum albumin was significantly lower with trends towards higher interleukin (IL)-6 and IL-8 in anemic compared to non-anemic patients. Further analysis by multiple logistic regression found that anemic patients treated with erythropoiesis stimulating agents had significantly higher odds for the upper two quartiles for IL-6, IL-8 and TNF-alpha compared to non-anemic patients. Our study found that the anemia of chronic kidney disease was associated with up regulation of TNF-alpha, and possibly IL-6 and IL-8 along with increased levels of these proinflammatory cytokines in patients treated with epoetin.

Topics: Aged; Anemia; Biomarkers; Case-Control Studies; Chronic Disease; Cytokines; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Inflammation; Interleukin-6; Interleukin-8; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Tumor Necrosis Factor-alpha; Up-Regulation

Polymorphonuclear leukocyte priming and low grade inflammation are related to severity of kidney disease. Erythropoietin-receptor is present on PMNLs. OBJECTIVESxi: To evaluate the effect of 20 weeks of epoetin-alpha treatment on PMNL characteristics in relation to the rate of kidney function deterioration in patients with chronic kidney disease.. Forty anemic chronic kidney disease patients, stage 4-5, were assigned to EPO and non-EPO treatment for 20 weeks. A group of 20 healthy controls was also studied. PMNL priming and PMNL-derived low grade inflammation were estimated, in vivo and ex vivo, before and after EPO treatment: The rate of superoxide release, white blood cells and PMNL counts, serum alkaline phosphatase and PMNL viability were measured. EPO-receptor on PMNLs was assayed by flow cytometry. The effect of 20 weeks of EPO treatment on kidney function was related to the estimated glomerular filtration rate. esults: EPO treatment attenuated superoxide release ex vivo and in vivo and promoted PMNL survival ex vivo. Decreased low grade inflammation was reflected by reduced WBC and PMNL counts and ALP activity following treatment. EPO retarded the deterioration in GFR. The percent of PMNLs expressing EPO-R was higher before EPO treatment and correlated positively with the rate of superoxide release. After 20 weeks of EPO treatment the percent of PMNLs expressing EPO-R was down-regulated.. These non-erythropoietic properties of EPO are mediated by EPO-R on PMNLs, not related to the anemia correction. A new renal protection effect of EPO via attenuation of PMNL priming that decreases systemic low grade inflammation and oxidative stress is suggested.

Topics: Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Glomerular Filtration Rate; Hematinics; Humans; Kidney Failure, Chronic; Male; Neutrophils; Oxidative Stress; Receptors, Erythropoietin; Recombinant Proteins; Severity of Illness Index; Superoxide Dismutase

Trials of anemia correction in chronic kidney disease have found either no benefit or detrimental outcomes of higher targets. We did a secondary analysis of patients with chronic kidney disease enrolled in the Correction of Hemoglobin in the Outcomes in Renal Insufficiency trial to measure the potential for competing benefit and harm from achieved hemoglobin and epoetin dose trials. In the 4 month analysis, significantly more patients in the high-hemoglobin compared to the low-hemoglobin arm were unable to achieve target hemoglobin and required high-dose epoetin-alpha. In unadjusted analyses, the inability to achieve a target hemoglobin and high-dose epoetin-alpha were each significantly associated with increased risk of a primary endpoint (death, myocardial infarction, congestive heart failure or stroke). In adjusted models, high-dose epoetin-alpha was associated with a significant increased hazard of a primary endpoint but the risk associated with randomization to the high hemoglobin arm did not suggest a possible mediating effect of higher target via dose. Similar results were seen in the 9 month analysis. Our study demonstrates that patients achieving their target had better outcomes than those who did not; and among subjects who achieved their randomized target, no increased risk associated with the higher hemoglobin goal was detected. Prospective studies are needed to confirm this relationship and determine safe dosing algorithms for patients unable to achieve target hemoglobin.

Topics: Aged; Anemia; Chronic Disease; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Renal Insufficiency; Risk; Treatment Outcome

Optimal hemoglobin targets for chronic kidney disease patients receiving erythropoiesis-stimulating agents remain controversial. The effects of different hemoglobin targets on blood transfusion requirements have not been well characterized, despite their relevance to clinical decision-making.. Five hundred ninety-six incident hemodialysis patients without symptomatic cardiac disease were randomly assigned to hemoglobin targets of 9.5 to 11.5 g/dl or 13.5 to 14.5 g/dl for 96 wk using epoetin alfa as primary therapy and changes in left ventricular structure as the primary outcome (previously reported). Patients were masked to treatment assignment. Blood transfusion data were prospectively collected at 4-wk intervals.. The mean age and prior duration of dialysis therapy of the study population were 50.8 and 0.8 yr, respectively. Previously reported mortality was similar in low and high-target subjects, at 4.7 (95% confidence interval 3.0, 7.3) and 3.1 (1.8, 5.4) per hundred patient years, respectively. Transfusion rates were 0.66 (0.59, 0.74) units of blood per year in low and 0.26 (0.22, 0.32) in high-target subjects (P < 0.0001). Hemoglobin level at transfusion (7.7 [7.5, 7.9]) versus 8.1 [7.6, 8.5] g/dl) were similar with both groups. High hemoglobin target was a significant predictor of time to first transfusion independent of baseline associations (hazard ratio = 0.42; 95% confidence interval = 0.26-0.67).. In hemodialysis patients with comparatively low mortality risks, normal hemoglobin targets may reduce the need for transfusions.

Topics: Anemia; Blood Transfusion; Canada; Chronic Disease; Epoetin Alfa; Erythropoiesis; Erythropoietin; Europe; Female; Hematinics; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome

The aim of this trial was to gather data on the long-term safety of a new erythropoietin preparation (epoetin zeta), focusing on the formation of anti-erythropoietin antibodies, when administered intravenously for maintenance of target hemoglobin concentration in anemic patients with end-stage renal failure receiving chronic hemodialysis. In addition, we aimed to provide information on the efficacy of epoetin zeta under open, noncontrolled conditions.. Patients received epoetin zeta intravenously, 1-3 times/week for 56 weeks (overall patient group, n=745) or 108 weeks (Bulgarian subgroup, n=164). The aim of treatment was to maintain hemoglobin values between 10.5 and 12.5 g/dL with constant epoetin dosage. Primary (safety) endpoints were the occurrence of anti-erythropoietin antibodies and the evaluation of adverse events (AEs). Secondary (efficacy) endpoints included the mean weekly dose of epoetin per kg of body weight and mean hemoglobin concentrations.. No patients developed neutralizing anti-erythropoietin antibodies. The most commonly reported AEs were infections and infestations (34.1%); followed by injury, poisoning, and procedural complications (25.8%); and gastrointestinal disorders (21.9%); 37.3% of patients reported serious AEs. The hemoglobin values remained stable, with mean values after 56 weeks of 11.3-11.6 g/dL for the overall group and 11.1-11.6 g/dL for the Bulgarian subgroup. The dosage of epoetin zeta was stable throughout the course of the trial. No cases of lack of (or loss of ) efficacy were observed in the course of the trial.. The evaluation of the primary endpoints provided data supporting the intravenous administration of epoetin zeta in patients with chronic renal failure. Neutralizing antibodies against erythropoietin were not detected, and there were no reports of patients with increasing erythropoietin resistance. Our results suggest that intravenous administration of epoetin zeta is effective regarding its ability to maintain stabilized hemoglobin levels within the target range of 10.5-12.5 g/dL.

Topics: Anemia; Blood Transfusion; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis

The aim of the study was to evaluate the effectiveness, safety, and clinical outcomes of erythropoietin therapy in the treatment of anaemic cancer subjects receiving chemotherapy and to examine hypochromic red blood cell measurement as an indicator of functional iron sufficiency and as a predictor of responsiveness or non-responsiveness to erythropoietin therapy.. Patients who had a non-myeloid malignancy, had Hb < or = 11.0 g/dL, had a life expectancy of more than 6 months, were 18 years or older, were receiving chemotherapy and would continue to be treated for at least 2 months were given s.c. epoetin alfa three times a week.. Haemoglobin levels increased significantly at all time periods compared with baseline and the number of transfusions received decreased significantly at all time periods compared with baseline. Quality of life as measured by Functional Assessment of Cancer Therapy-Anaemia showed significant increases at months 2 and 4 and there were significant improvements in the fatigue subscale at both time points (P < 0.05). Significant improvements at end-point were observed for the physical, emotional and functional well-being, and additional concern subscales (all P < 0.05). Haematocrit and reticulocytes increased significantly at end-point compared with at baseline (haematocrit 33.4 vs 28.3%, P < 0.001; reticulocytes 105.8 vs 78.6 x 10(9)/dL, P = 0.005). The percentage of hypochromic red blood cells did not show predictive value for response to treatment status.. Epoetin alfa improved haemoglobin levels and quality of life in anaemic cancer patients receiving chemotherapy.

Topics: Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Australia; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; New Zealand; Predictive Value of Tests; Prospective Studies; Recombinant Proteins; Time Factors; Treatment Outcome

To evaluate the therapeutic efficacy and safety of epoetin zeta, compared with epoetin alfa, in maintaining target haemoglobin (Hb) concentrations in patients with anaemia and chronic kidney disease (CKD) maintained on haemodialysis.. Patients received epoetin zeta or epoetin alfa intravenously, 1-3 times/week for 12 weeks, then the alternative treatment for 12 weeks, in this double-blind, crossover, phase III trial. Eligible patients were 18-75 years old with CKD stage 5 maintained on haemodialysis. Patients had received epoetin for > or = 3 months upon study entry and had achieved a target Hb level of 10.5-12.5 g/dL with a stable epoetin dose.. Primary efficacy endpoints were intra-individual differences (test-reference) in mean Hb levels and mean weekly dose/kg of body weight. Safety endpoints included occurrence of neutralizing anti-erythro poietin antibodies, tolerability, and adverse events (AEs).. In total, 313 patients were randomized to receive epoetin zeta (n = 155) or epoetin alfa (n = 158); 146 and 145 patients (respectively) switched treatment after 12 weeks. Mean (range) Hb levels were 11.35 (8.96-14.22) g/dL and 11.54 (8.74-13.84) g/dL for patients receiving epoetin zeta and epoetin alfa, respectively (95% confidence interval [CI] [test-reference]: 0.09-0.28 g/dL, within the predefined equivalence range of +/-0.6 g/dL). Mean (range) weekly doses were 92.68 (12.74-398.41) IU/kg/wk and 92.58 (10.53-393.07) IU/kg/wk for patients receiving epoetin zeta and epoetin alfa, respectively (95% CI [test-reference]: -4.67 and 4.29 IU/kg/wk, within the equivalence range of +/-45.00 IU/kg/wk). Patients underwent minor nominal dose adjustments during treatment crossover. AE profile was similar for both products; the most commonly reported AEs were infections and infestations (in 26.5% of patients receiving epoetin zeta and 23.6% receiving epoetin alfa). No patients developed neutralizing anti-erythropoietin antibodies.. Epoetin zeta is therapeutically equivalent to epoetin alfa in the maintenance of target Hb levels in patients with renal anaemia. No unexpected AEs were seen.

Topics: Adult; Aged; Anemia; Cross-Over Studies; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Therapeutic Equivalency

Anemia, a common hematological abnormality in HIV, contributes to decreased quality of life (QOL). This study assessed once-every-2-week epoetin alfa on maintaining QOL and hemoglobin (Hb) in anemic HIV-infected patients in a 24-week, open-label, multicenter study. HIV-infected patients (Hb < or =12 g/dl) received epoetin alfa 40,000 units subcutaneously once weekly, until reaching Hb > or =13 g/dl. Patients then entered a maintenance phase (MP), in which epoetin alfa was administered every other week or at longer intervals. The trial objectives were to determine if QOL, as measured by the Medical Outcomes Study-HIV (MOS-HIV) general health perceptions (GHP) domain and Hb, was maintained. Safety was also assessed. A total of 292 patients were enrolled (72% on HAART). Mean baseline laboratory values were Hb = 10.8 g/dl, CD4(+) count = 280 cells/microl, and HIV RNA = 51,867 copies/ml. In all, 81% of patients reached Hb > or =13 g/dl and 92% reached Hb > or =12 g/dl. QOL was maintained from the beginning (GHP = 44.2 points) to the end of MP (GHP = 43.4 points) with every other week or longer dosing. Mean Hb at the beginning of MP was 13.4 +/- 0.5 g/dl and was 12.8 +/- 1.4 g/dl at study end. Epoetin alfa was well tolerated; adverse events were consistent with those reported in previous studies of epoetin alfa in HIV-infected patients. Although the clinical approach tested in this study is not consistent with current prescribing recommendations, the results confirm the efficacy of prolonged dosing intervals (every 2-4 weeks) in maintaining optimal Hb levels and QOL in anemic HIV-infected patients.

Topics: Adult; Aged; Anemia; CD4 Lymphocyte Count; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; HIV Infections; Humans; Injections, Subcutaneous; Male; Middle Aged; Quality of Life; Recombinant Proteins; Treatment Outcome; Viral Load

This study compared the effects of early intervention with standard use of epoetin alfa on haemoglobin (Hb) levels and transfusion requirements in cancer patients receiving chemotherapy. Patients with Hb>10 and < or= 12 g/dL were randomised 1:1 to epoetin alfa (40,000 IU, subcutaneously, once weekly), initiated within 7d of the start of the first on-study chemotherapy cycle (defined as early intervention) versus epoetin alfa when Hb

Topics: Adolescent; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Survival Analysis; Treatment Outcome

To assess the therapeutic equivalence of epoetin zeta and epoetin alpha for correction of haemoglobin (Hb) concentration in patients with anaemia and chronic kidney disease (CKD) stage 5 maintained on haemodialysis.. In total, 609 patients with CKD and anaemia (Hb < 9 g/dL) were randomly assigned to receive either epoetin zeta or epoetin alpha intravenously, one to three times per week for 24 weeks. Dosing was titrated individually to achieve a stable, target Hb concentration of 11-12 g/dL. Primary endpoints were the mean weekly dose of epoetin per kilogram of body weight and mean Hb concentration during the last 4 weeks of treatment. Safety endpoints were the occurrence of anti-erythropoietin antibodies, ratings of tolerability and adverse events (AEs).. Mean (+/- standard deviation [SD]) Hb concentration over the last 4 weeks of treatment was 11.61 +/- 1.27 g/dL for patients receiving epoetin zeta, compared with 11.63 +/- 1.37 g/dL for patients receiving epoetin alpha (95% confidence interval [CI]: -0.25 to 0.20 g/dL). Mean (+/- SD) epoetin zeta weekly dose over the last 4 weeks of treatment was 182.20 +/- 118.11 IU/kg/wk, compared with 166.14 +/- 109.85 IU/kg/wk for epoetin alpha (95% CI: -3.21 to 35.34 IU/kg/wk). The most commonly reported AEs (> 5% of patients) were infections and infestations (12.5% and 12.8% of patients treated with epoetin zeta and epoetin alpha, respectively) and vascular disorders (8.5% and 8.9%, respectively). No patients developed neutralizing anti-erythropoietin antibodies.. Epoetin zeta, administered intravenously, is therapeutically equivalent to epoetin alpha in the correction of low Hb concentration in patients with CKD undergoing haemodialysis. No unexpected AEs were seen and both epoetin zeta and epoetin alpha were well tolerated.

Topics: Adolescent; Adult; Aged; Anemia; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Risk Assessment; Severity of Illness Index; Therapeutic Equivalency; Treatment Outcome

Although epoetin alfa is commonly initiated weekly (QW) in anemic chronic kidney disease (CKD) patients, recent evidence indicates that it can be initiated every 2 wk (Q2W) and used in maintenance therapy every 4 wk (Q4W). This study examined the feasibility of initiating epoetin alfa Q4W in anemic CKD patients not receiving dialysis.. This open-label study randomized subjects (1:2:2:2) to treatment with epoetin alfa 10,000 IU QW, 20,000 IU Q2W, 20,000 IU Q4W, or 40,000 IU Q4W for 16 wk. Subjects were > or =18 yr, had hemoglobin <11 g/dl, a glomerular filtration rate of 15 to 90 ml/min per 1.73 m(2), and had not received erythropoietic therapy within 8 wk. The primary analysis was a noninferiority comparison of the 40,000 IU Q4W to the 20,000 IU Q2W group in the per-protocol population with respect to hemoglobin change from baseline to the end of study.. Of 262 subjects randomized, 229 comprised the per-protocol population. Mean hemoglobin change from baseline for the 40,000 IU Q4W group (1.24 g/dl) was not inferior to the 20,000 IU Q2W group (1.11 g/dl) with the lower limit of 95% CI, -0.21 g/dl. In the QW, 20,000 IU Q2W, 20,000 IU Q4W, and 40,000 IU Q4W groups, 90%, 87%, 75%, and 86% of subjects, respectively, achieved a hemoglobin increase > or =1 g/dl. Serious adverse events were similar across all groups.. Epoetin alfa can be initiated Q4W in anemic CKD subjects.

Topics: Aged; Aged, 80 and over; Anemia; Chronic Disease; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Feasibility Studies; Female; Ferritins; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Iron Compounds; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Transferrin; Treatment Outcome; United States

Emerging evidence suggests that epoetin alfa can be administered at extended intervals of up to 4 wk. This open-label, randomized study was performed to characterize the pharmacokinetic and pharmacodynamic profiles of four dosing regimens of epoetin alfa administered subcutaneously in anemic patients who had chronic kidney disease and were not on dialysis.. Thirty-eight patients, enrolled from nine centers in the United States, were > or =18 yr of age and had hemoglobin <11.0 g/dl and GFR 12 to 60 ml/min per 1.73 m(2). Patients received one of four epoetin alfa dosing regimens: 50 IU/kg three times per week, 10,000 IU once weekly, or 20,000 IU every 2 wk for 36 d or 40,000 IU every 4 wk for 64 d. Each regimen provided a similar dosage of epoetin alfa over 4 wk. Dosage adjustments were not permitted.. Drug exposure to epoetin alfa over 4 wk, based on area under the curve, was somewhat higher with the extended interval regimens compared with the three-times-weekly regimen. Mean change in hemoglobin during the study period was similar for all regimens. No patients were transfused. Three patients experienced five serious adverse events, none of which was considered treatment related.. Extended dosing interval regimens of epoetin alfa yielded modest pharmacokinetic differences but a similar pharmacodynamic response, suggesting that less frequent, higher dosages of epoetin alfa may be as effective as the current three-times-weekly regimen in anemic patients who have chronic kidney disease and are not on dialysis.

Topics: Aged; Aged, 80 and over; Anemia; Chronic Disease; Dialysis; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Count; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Diseases; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Reticulocyte Count; Treatment Outcome; United States

Among hemodialysis patients, achieved hemoglobin is associated with Epoetin alfa dose and erythropoietin responsiveness. A prospective erythropoietin responsiveness measure was developed and its association with mortality evaluated.. Data from 321 participants were used and randomized to the hematocrit normalization arm of the Normal Hematocrit Cardiac Trial. Subjects were to receive a 50% Epoetin alfa dose increase at randomization. The prospective erythropoietin responsiveness measure was defined as the ratio of weekly hematocrit change (over the 3 wk after randomization) per Epoetin alfa dose increase (1000 IU/wk) corresponding to the mandated 50% dose increase at randomization. The distribution of responsiveness was divided into quartiles. Over a 1-yr follow-up, Cox proportional hazard modeling evaluated associations between this responsiveness measure and mortality.. Erythropoietin responsiveness values ranged from -2.1% to 2.4% per week per 1000 IU. Although subjects were similar across response quartiles, mortality ranged between 14% and 34% among subjects in the highest and lowest response quartiles (P = 0.0004), respectively. After adjusting for baseline prognostic indicators, highest versus lowest responsiveness was associated with a hazard ratio of 0.41 (95% confidence interval, 0.20 to 0.87).. Lower erythropoietin responsiveness is a strong, independent predictor of mortality risk and should be considered when evaluating associations between clinical outcomes and potential prognostic indicators, such as Epoetin alfa dose and achieved hemoglobin values.

Topics: Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Proportional Hazards Models; Recombinant Proteins; Renal Dialysis; Risk Assessment; Survival Analysis; Treatment Outcome

To determine the effect of aerobic and strength resistance training and epoetin alfa (EPO) therapy on transfusions, stem cell collections, transplantation recovery, and multiple myeloma treatment response.. Randomized clinical trial.. A myeloma research and therapy center in the south central United States.. 135 patients with multiple myeloma, 120 evaluable.. Random assignment to exercise or usual care groups. All patients received EPO based on an algorithm. Aerobic capacity, using the six-minute walk test, was assessed prior to induction chemotherapy, prior to stem cell mobilization, and following stem cell collection for all patients and before and after transplantation for patients continuing in the study. Data analysis included analysis of variance to compare other outcome variables by groups.. Number of red blood cell and platelet transfusions during transplantation, number of attempts at and total number of days of stem cell collection, time to recovery after transplantation, and response to intensive therapy for multiple myeloma.. Recovery and treatment response were not significantly different between groups after transplantation. The exercise group had significantly fewer red blood cell transfusions and fewer attempts at stem cell collection. Serious adverse events were similar in each group.. Exercise with prophylactic EPO therapy reduces the number of RBC transfusions and attempts at stem cell collection for patients receiving intensive treatment for multiple myeloma.. Exercise is safe and has many physiologic benefits for patients receiving multiple myeloma treatment.

Topics: Adult; Aged; Analysis of Variance; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Dexamethasone; Doxorubicin; Epoetin Alfa; Erythropoietin; Etoposide; Exercise Test; Exercise Therapy; Fatigue; Female; Hematinics; Humans; Male; Middle Aged; Multiple Myeloma; Nurse's Role; Nursing Evaluation Research; Oncology Nursing; Peripheral Blood Stem Cell Transplantation; Recombinant Proteins; Treatment Outcome; Vincristine

In patients with chronic renal failure, the ability to reduce the administration frequency of subcutaneous (SC) erythropoietin (epoetin) could provide benefits and may improve compliance. The study investigated whether once-weekly SC epoetin alfa was equivalent to twice- or thrice-weekly SC administration in maintaining anaemia correction in haemodialysis patients.. Eighty-three patients were randomly assigned to either once-weekly epoetin alfa (n = 44) or their original dose twice- or thrice-weekly regimen (control, n = 39) for 12 weeks. The haemoglobin concentration was maintained within the target range of 9.0-12.0 g/dL by adjusting the dose of epoetin alfa. All patients received intravenous iron supplementation, as required.. Stable haemoglobin levels were maintained without epoetin dose increases in the majority of patients in both groups (once-weekly group, 95.0%, control group, 91.4%). The mean haemoglobin levels at randomization at weeks 4, 8 and 12 were 10.7, 11.1, 11.3 and 11.0 g/dL, respectively, in the once-weekly group, and 10.5, 11.3, 11.5 and 11.3 g/dL, respectively, in the control group. The mean weekly dose of epoetin alfa at randomization at weeks 4, 8 and 12 was 142.8, 114.5, 108.6 and 104.5 IU/kg, respectively, in the once-weekly group, and 128.4, 116.0, 101.0 and 96.1 IU/kg/week, respectively, in the control group. No statistically significant between-group differences were apparent for changes in haemoglobin levels or epoetin alfa dosages at week 12.. This study demonstrates that once-weekly SC administration of epoetin alfa is as effective and safe as two or three times weekly administration in maintaining haemoglobin levels. Therefore, the once-weekly therapy using high dose of epoetin alfa is considered to be an efficient method in stable haemodialysis patients.

Topics: Aged; Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

This multicentre, open-label prospective, randomized, comparative-group study evaluated the effects of maintaining haemoglobin (Hb) in pre-dialysis chronic kidney disease (CKD) patients.. A total of 197 patients were randomized to start subcutaneous epoetin-alpha (SC-EPO; EPREX; 1000 U twice weekly) at an early stage of anaemia to maintain Hb at 11.0 +/- 1.0 g/dl (group A, n = 65), or to allow Hb to fall to < or =9.0 g/dl before starting SC-EPO (group B, n = 132) (2000 U three times weekly); and subsequently maintaining Hb at 11.0 +/- 1.0 g/dl.. Of 132 patients randomized to group B, 55 progressed to treatment (-trigger). The study was prematurely terminated due to contraindication of the subcutaneous administration route. Mean weekly EPO doses at 1 year were 1471 U for group A; 820 U for group B; final doses were 2281 U for group A; 2099 U for group B. There was no significant difference between groups A and B with regard to left ventricular mass (-12.5 vs -9.7%; P = 0.82). In groups A and B, 48% and 52%, respectively, terminated the study because of dialysis/death, after a median of 36.3 and 27.3 months, respectively.. Early intervention to correct anaemia in CKD patients did not have a significant impact on LVM, the primary efficacy variable. Time to dialysis/death was not significantly different between groups A and B.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome

The required erythropoiesis-stimulating agent (ESA) dose varies when correcting anaemia in chronic kidney disease (CKD) patients. This analysis was performed to identify the prevalence of and factors associated with ESA hyporesponsiveness.. This analysis was a post hoc evaluation of epoetin alfa dosage requirements in a subgroup of patients from the Effect of early Correction of Anemia on the Progression of CKD study. The patients in this subgroup were randomly assigned to the high haemoglobin target group (14-15 g/dl for men and 13-14 g/dl for women) and completed a 4-month haemoglobin stabilization phase with complete epoetin dosage data. The relationship of demographics, disease characteristics and laboratory measures with epoetin dosage were evaluated using Pearson's correlation, association measures and analysis of covariance (ANCOVA) models.. Of the 93 patients evaluated in this subgroup analysis, 14 (15%) were hyporesponsive to epoetin (maximum dosage >100 IU/kg/week during stabilization). An ANCOVA analysis showed that 52% of the observed variability in epoetin dosage at completion of the stabilization phase could be accounted for by diabetes as the primary cause of kidney disease, angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) use, proteinuria, transferrin saturation, age, pre-treatment haemoglobin, geographical region, serum iron and body mass index (BMI). Unidentified patient characteristics accounted for an additional 16% of the dosage variance.. Older age, higher BMI, anaemia, ACE inhibitor/ARB use and diabetes as the primary cause of kidney disease are associated with increased epoetin requirements when normalizing haemoglobin in anaemic CKD patients.

Topics: Adolescent; Adult; Aged; Anemia; Australia; Canada; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Europe; Female; Follow-Up Studies; Glomerular Filtration Rate; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Treatment Outcome

To evaluate the safety and efficacy of intravenous (IV) sodium ferric gluconate complex (FG), oral ferrous sulfate, or no iron to increase hemoglobin (Hb) in anemic cancer patients receiving chemotherapy and epoetin alfa.. In this open-label, multicenter trial, 187 patients with chemotherapy-related anemia (Hb <11 g/dl; serum ferritin > or =100 ng/ml or transferrin saturation > or =15%) scheduled to receive chemotherapy and epoetin alfa (40,000 U subcutaneously weekly) were randomized to 8 weeks of 125 mg of IV FG weekly, 325 mg of oral ferrous sulfate three times daily, or no iron. The primary outcome was a change in Hb from baseline to endpoint, first whole-blood or red blood cell transfusion, or study withdrawal.. One hundred twenty-nine patients were evaluable for efficacy (FG, n = 41; oral iron, n = 44; no iron, n = 44). Mean increase in Hb was 2.4 g/dl (95% confidence interval [CI], 2.1-2.7) for FG (p = .0092 vs. oral iron; p = .0044 vs. no iron), 1.6 g/dl (95% CI, 1.1-2.1) for oral iron (p =.7695 vs. no iron), and 1.5 g/dl (95% CI, 1.1-1.9) for no iron. Hb response (increase > or =2 g/dl) was 73% for FG (p = .0099 vs. oral iron; p = .0029 vs. no iron), 46% for oral iron (p = .6687 vs. no iron), and 41% for no iron. FG was well tolerated.. For cancer patients with chemotherapy-related anemia receiving epoetin alfa, FG produces a significantly greater increase in Hb and Hb response compared with oral iron or no iron, supporting more aggressive treatment with IV iron supplementation for these patients.

Topics: Administration, Oral; Aged; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Ferric Compounds; Hematinics; Humans; Iron; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins

Previous trials have suggested a quality-of-life (QOL) improvement for anemic cancer patients treated with erythropoietin, but few used QOL as the primary outcome. We designed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung (NSCLC).. A multicenter, randomized, double-blind, placebo-controlled trial was conducted. The proposed sample size was 300 patients. Eligible patients were required to have NSCLC unsuitable for curative therapy and baseline hemoglobin (Hgb) levels less than 121 g/L. Patients were assigned to 12 weekly injections of subcutaneous epoetin alpha or placebo, targeting Hgb levels between 120 and 140 g/L. The primary outcome was the difference in the change in Functional Assessment of Cancer Therapy-Anemia scores between baseline and 12 weeks.. Reports of thrombotic events in other epoetin trials prompted an unplanned safety analysis after 70 patients had been randomly assigned (33 to the active arm and 37 to the placebo arm). This revealed a significant difference in the median survival in favor of the patients on the placebo arm of the trial (63 v 129 days; hazard ratio, 1.84; P = .04). The Steering Committee closed the trial. Patient numbers compromised the interpretation of the QOL analysis, but a positive Hgb response was noted with epoetin alfa treatment.. An unplanned safety analysis suggested decreased overall survival in patients with advanced NSCLC treated with epoetin alfa. Although infrequent, other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Canada; Carcinoma, Non-Small-Cell Lung; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Proportional Hazards Models; Quality of Life; Recombinant Proteins; Thrombosis; Time Factors; Treatment Outcome

To compare the effectiveness of darbepoetin alfa with epoetin alfa (recombinant human erythropoietin [rHuEPO]) for achieving transfusion independence and increasing hemoglobin concentrations in critically ill patients.. Retrospective, descriptive study.. Level I trauma center intensive care units.. Seventy-two patients who spent at least 3 days in the cardio-thoracic, medical, or surgery-trauma intensive care units and received at least one weekly dose of rHuEPO 40,000 units (33 patients) or darbepoetin alfa 100 microg (39 patients).. Number of rHuEPO and darbepoetin alfa doses, hemoglobin concentrations, and cumulative number of transfusions were recorded for up to 28 days after the first dose was given, and the data were statistically analyzed. Beginning a median of 10 days after the patients were admitted to the intensive care unit, they received a median of 3.5 doses of darbepoetin alfa or 4 doses of rHuEPO. Mean hemoglobin concentrations at which treatment with darbepoetin alfa and rHuEPO were started were 8 and 8.2 g/dl, respectively (p=0.41). Transfusion independence was achieved in 44% of patients in the darbepoetin alfa group compared with 36% of patients in the rHuEPO group (p=0.63). Patients in both groups received a mean of 2.7 units of packed red blood cells during the 28-day study period. The mean change in hemoglobin levels from baseline over time did not significantly differ between groups (p=0.75).. Patients receiving darbepoetin alfa 100 microg/week and those receiving rHuEPO 40,000 units/week for anemia of critical illness achieved similar rates of transfusion independence and increases in hemoglobin concentrations from baseline at 28 days. Compared with previously published studies, erythropoietic agents were administered late in the course of critical illness in response to low hemoglobin concentrations.

Topics: Adult; Aged; Anemia; Blood Transfusion; Critical Care; Critical Illness; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Intensive Care Units; Iron Compounds; Male; Middle Aged; Recombinant Proteins; Retrospective Studies; Time Factors; Trauma Centers; Treatment Outcome

This randomized trial assessed the effect of recombinant human erythropoietin (EPO) vs preoperative autologous donation (PAD) on postoperative vigor and handgrip strength in patients undergoing primary total joint arthroplasty. Adults with baseline hemoglobin level of 11 to 14 g/dL received EPO (600 IU/kg once weekly for 4 doses, n = 130) or PAD (n = 121) before primary, unilateral hip or knee arthroplasty. Mean changes in vigor score and handgrip strength from baseline were not significantly different between treatment groups. Multivariate analyses found a significant treatment effect favoring EPO over PAD for vigor, but not for handgrip strength. Patients in the EPO group had higher hemoglobin levels and required fewer transfusions. Both treatments were well tolerated. Additional study is needed to elucidate the influence of blood management strategies on postoperative vigor.

Topics: Activities of Daily Living; Aged; Anemia; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Transfusion, Autologous; Epoetin Alfa; Erythropoietin; Female; Hand Strength; Health Status; Health Status Indicators; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Postoperative Complications; Postoperative Period; Recombinant Proteins

This study evaluated the safety/efficacy of once-weekly (QW) epoetin alfa measured by quality of life (QOL), hemoglobin (Hb), transfusion incidence, tumor response, and survival in patients with chemotherapy-naïve, advanced non-small cell lung cancer (NSCLC).. Stage IIIB/IV NSCLC patients with Hb > or = 11 to < 15 g/dl scheduled for at least 8 weeks of first-line chemotherapy were randomized to subcutaneously receive 40,000 U of epoetin alfa QW at chemotherapy initiation (immediate) or no epoetin alfa unless Hb decreased to < or = 10 g/dl (delayed). The primary efficacy variable was change in QOL for immediate versus delayed intervention. Target accrual was 320 patients.. The study was terminated early because of slow accrual; of 216 patients enrolled, 211 were evaluable for efficacy. Hb was maintained in the immediate group, but it decreased in the delayed group (12.9 versus 11.6 g/dl final values, respectively). Numerically, fewer immediate patients required transfusions versus delayed patients. Mean QOL scores, modestly declining in both groups from baseline to final measurement, were not significantly different between groups. Tumor response and median overall survival were similar between groups. Epoetin alfa was well tolerated, with a similar thrombovascular event rate between groups.. Epoetin alfa in subcutaneous doses of 40,000 U QW, given immediately at chemotherapy initiation for advanced NSCLC, was well tolerated, and it effectively maintained Hb, leading to a reduced transfusion incidence versus delayed epoetin alfa. Overall QOL scores were higher than typical in this population, decreasing slightly during treatment in both groups. Overall survival was similar between groups, with no evidence of a negative effect by early epoetin alfa intervention.

Topics: Aged; Anemia; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Recombinant Proteins; Survival Analysis; Time Factors

Anemia is frequently associated with cancer due to the disease itself and antineoplastic treatments. This open-label, uncontrolled, multi-center study evaluated the effects of once-weekly (qw) epoetin alfa 40,000 IU on hemoglobin (Hb) levels and quality of life (QoL) in anemic patients receiving chemotherapy for solid tumors.. A total of 522 patients with Hb level < or =12 g/dL received epoetin alfa 40,000 IU qw subcutaneously for 9-20 weeks to reach and maintain Hb range of 12-14 g/dL. QoL was assessed with the Functional Assessment of Cancer Therapy-Anemia (FACT-An [anemia sub-scale]) and Cancer Linear Analogue Scale (CLAS) at study entry, after two chemotherapy cycles, and at study end.. Mean baseline Hb was 10.43 g/dL. Hb increases (g/dL) from baseline after 4, 8, 12 weeks and at study end were 1.07, 1.77, 1.92 and 1.71 g/dL, respectively. Response rates (Hb increase > or =1 and > or =2 g/dL during trial) were 81% and 61%, respectively. Mean increases in the FACT-An score from baseline (mean 55.4) were 3.1 after two chemotherapy cycles and 3.3 at study end; mean increases in the CLAS score from baseline (58.4 mm) were 5.9 mm after two chemotherapy cycles and 6.5 mm at study end.. The greatest QoL increase was recorded when patients approached Hb level of 12 g/dL, independent of the baseline Hb level. Hb changes from baseline to trial end were related to corresponding changes in the FACT-An score. A positive correlation was also observed in patients with progressive disease. Adverse events were essentially those associated with chemotherapy. Incidence of thrombovascular events (6.7%) did not differ from the expected standard treatment in cancer patients. Epoetin alfa 40,000 IU qw increased Hb levels and improved or preserved QoL.

Topics: Aged; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins

The purpose of this study was to evaluate the safety and efficacy of epoetin alfa (EPO) at an initial dose of 60,000 Units (U) once weekly (QW) followed by extended dosing of 80,000 U every 3 weeks (Q3W) in patients with chemotherapy-induced anemia (CIA).. Anemic patients (hemoglobin [Hb] < or = 11 g/dl) receiving Q3W chemotherapy for nonmyeloid malignancy were enrolled in this prospective, open-label, single-arm study to receive EPO 60,000 U subcutaneously (SC) QW (initial dosing phase [IDP]) until a target Hb level of 12 g/dl was reached (maximum 12 weeks). Patients who achieved an Hb level of 12 g/dl at any point during the IDP then entered the extended dosing phase (EDP; EPO 80,000 U SC Q3W). Maximum study duration (IDP + EDP) was 24 weeks. The primary endpoint was the proportion of patients achieving a hematopoietic response (Hb increase > or = 2 g/dl from baseline or Hb > or = 12 g/dl) during the IDP.. One hundred fifteen patients were enrolled. During the IDP, 76% (84/110) of patients achieved a hematopoietic response, and 15% (17/115) received red blood cell (RBC) transfusion. Sixty-three percent (73/115) of patients entered the EDP, and 88% (64/73) of these patients maintained a mean Hb level > 11.0 and < or =13.0 g/dl. Two of 73 patients received RBC transfusion during the EDP. Adverse events were consistent with the underlying disease and chemotherapy treatment.. These results suggest that initiation of EPO 60,000 U SC QW is effective in the treatment of CIA and that EPO 80,000 U SC Q3W can be an effective extended dosing option.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins; Treatment Outcome

Anaemia seriously threatens the quality of life (QOL) in cancer patients receiving chemotherapy. In this article results are presented on the lung cancer population from a Dutch observational study. This study addressed the real-life situation of recombinant human erythropoietin (r-Hu-EPO or epoetin alfa) treatment in anaemic cancer patients receiving chemotherapy, with a focus on efficacy. In total 781 patients were enrolled in the observational study, including 382 patients with lung cancer. At enrolment patients were receiving epoetin alfa treatment and/or patients had a haemoglobin (Hb) level 11.3g/dl) was especially effective for NSCLC patients where it resulted in a stabilization of Hb at baseline level. For SCLC patients this strategy was less effective. Furthermore, early intervention seemed to diminish the need for a blood transfusion, i.e., the higher the Hb at epoetin initiation the more patients did not receive any blood transfusion. Results from this observational study demonstrate that epoetin alfa treatment corrects chemotherapy-related anaemia in both NSCLC as well as SCLC patients. Early epoetin alfa intervention seems advantageous for lung cancer patients both in terms of maintaining adequate Hb levels during che

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Carcinoma, Non-Small-Cell Lung; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Netherlands; Quality of Life; Recombinant Proteins

A continuous erythropoietin receptor activator (C.E.R.A.) is currently in development for the treatment of anemia in patients with chronic renal disease (CRD) receiving or not receiving dialysis treatment.. The objectives of this study were to determine the optimal dose and administration schedule for IV C.E.R.A. in patients with CRD previously treated with IV epoetin alfa TIW, and to assess its tolerability profile in these patients. In addition, a 12-month extension phase was used to assess the long-term efficacy and tolerability of C.E.R.A.. This randomized, open-label, dose-finding study was conducted at 14 study centers across the United States. Male and female patients aged >/=18 years with CRD and CRD-related anemia and receiving treatment with IV epoetin alfa were enrolled. After a 2-week run-in period in which all patients continued to receive their previous epoetin treatment TIW, patients were switched to C.E.R.A. at 1 of 3 doses, determined by multiplying the previous weekly epoetin dose by 1 of 3 ratios (0.25 pg/150 IU, 0.4 pg/150 IU, or 0.6 pg/150 IU). Within each dose group, patients were randomized to 1 of 2 frequency subgroups: QW or Q2W Dose adjustments were not permitted during the first 6 weeks; the total dose during this period was the same for a particular dose group across the frequency subgroups. The primary efficacy parameter was change in hemoglobin (Hb) standardized to a 6-week period between baseline and the point when the patient had a dose change or blood transfusion, thus providing an estimate of Hb change based on starting dose. Following completion of a 19-week core period, patients could enter the 12-month extension period, aiming to maintain Hb concentrations between 11 and 12 g/dL. Adverse events (AEs) were recorded in the patients' case-report forms by the investigators throughout the study.. A total of 91 patients entered the core period (mean age, 58 years; 66% male); 10 patients withdrew prematurely during this period (4 owing to AEs and 6 for other reasons). Fifty-three patients continued into the extension period; 22 patients withdrew during this period (6 because of AEs, and 16 for other reasons). There was a significant dose-response effect (P < 0.001) and a significant effect of schedule (P < 0.002) for the primary efficacy end point. Stable Hb concentrations were maintained throughout the study (11-12 g/dL, with a narrow 95% CI). No significant difference between schedules was observed during the extension period, and few dose changes were required (mean, 4 and 2 per patient per year in the QW and Q2W groups, respectively). Nineteen and 22 patients experienced serious AEs during the core and extension periods, respectively, but only 1 event was considered related to study treatment. The most frequent AEs were headache and vomiting during the core study period and dizziness, fatigue, chest pain, and pyrexia during the extension period.. In this study, N C.E.R.A. provided effective maintenance of Hb concentrations in patients receiving dialysis treatment who were switched directly from N epoetin alfa TIW to N C.E.R.A. QW or Q2W C.E.R.A. was generally well tolerated.

Topics: Analysis of Variance; Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Regression Analysis; Renal Dialysis

Anemia is a common problem in the cancer population that is the result of clinical consequences. It also has adverse effects on patients' perceived quality of life. Good management of anemia in the cancer population is therefore essential. A recent published clinical trial has demonstrated statistically significant increases in hemoglobin levels and significantly increased QOL assessment following the administration of recombinant erythropoietin.. To evaluate the effectiveness, the safety, and the quality of life by using once weekly dosing of Epoetin alfa (Eprex, Janssen-cilag) 40,000 units in the treatment of anemia in cancer patients receiving chemotherapy.. Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University Bangkok, Thailand.. This was an open label, non-randomized study, in 41 adult male and female anemic cancer patients who had non-myeloid malignancies in the upper area of the body part and hemoglobin ranging from 9-11 g/dL receiving chemotherapy at least 8 weeks with or without concurrent radiotherapy. The subjects were treated with Epoetin alfa 40,000 units once a week subcutaneously. If, the hemoglobin did not increase by > 1.0 g/dl after 4 weeks of treatment, the dose of Epoetin alfa was then increased to 60,000 units per dose subcutaneously at week 5. The Epoetin alfa treatment would continue for a total of 16 weeks. Clinical outcome was evaluated based on quality of life by using the linear analog scale assessment (LASA) and the functional assessment of cancer therapy-anemia (CU-QOL) instrument. Analyses were performed to determine the incremental change in QOL associated with hemoglobin increases.. Seventy six percent of patients receiving Epoetin alfa subcutaneously showed good response with hemoglobin increases of > or = 1 g/dL (Hb level before and after = 9.82 +/- 0.78 g/dL and 12.56 +/- 1.49 g/dL, respectively; p < 0. 001). Improvement of all primary cancer- and anemia-specific QOL domains, including energy level and ability to do daily activities evaluated from LASA and fatigue assessed from CU-QOL, were significantly greater (p < 0.01) for week 16 (233.94 +/- 56.01 and 18.45 +/- 13.07) compared to the baseline (202.58 +/- 36.74 and 25.09 +/- 11.00). Epoetin alfa was well tolerated in all patients.. Once weekly dosing of Epoetin alfa 40,000 units therapy is safe and effective in remodeling anemia and significantly improves the quality of life in cancer patients receiving chemotherapy. Therefore, the physician should maintain hemoglobin concentration of cancer patients in normal level to improve their quality of life through the chemotherapy period.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Surveys and Questionnaires; Treatment Outcome

Epoetin delta is an epoetin that, unlike existing agents, is produced in a human cell line. The present study investigated the efficacy and tolerability of intravenous (i.v.) epoetin delta compared with i.v. epoetin alfa.. This was a 6-month, multicentre, randomized, double-blind trial in haemodialysis patients previously receiving epoetin alfa. Haematological parameters were assessed, and adverse events monitored. Equivalent efficacy was defined as a difference in mean haemoglobin between the two agents over weeks 12-24 of < or = 1 g/dl with a 90% confidence interval (CI) within the range -1 to 1 g/dl.. In total, 560 patients received epoetin delta while 192 received epoetin alfa, and 76.8% and 79.7% of patients, respectively, completed the study. Both agents showed similar efficacy in controlling anaemia: the point estimate for the difference in mean haemoglobin over weeks 12-24 was 0.01 g/dl (90% CI, -0.13, 0.15 g/dl), confirming equivalence. Adverse events were those expected in dialysis patients. Events possibly related to treatment occurred in 9.2% of patients receiving epoetin delta and 8.4% receiving epoetin alfa. Serious adverse events (SAEs) occurred in 33.0% and 26.7% of patients in the epoetin delta and epoetin alfa groups, respectively. Six patients in the epoetin delta group experienced an SAE considered possibly related to treatment (mostly access-related clotting), compared with no patient in the epoetin delta group. None of these SAEs were life threatening.. Epoetin delta was shown to have an equivalent efficacy and safety profile to epoetin alfa in this 6-month study.

Topics: Aged; Anemia; Blood Transfusion; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Research Design; Time Factors

To evaluate the effect of epoetin alfa treatment on hemoglobin (Hb), fatigue, quality of life (QOL), and mobility in elderly patients with chronic anemia.. An exploratory, 32 week, randomized, double-blind, crossover treatment trial.. Sixty-two community-dwelling individuals aged 65 and older with chronic anemia (Hb < or =11.5 g/dL).. Subcutaneous epoetin alfa or placebo weekly for 16 weeks (Phase I) with crossover to the opposite treatment (Phase II).. Hb and QOL scores from the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system. Mobility was assessed as a secondary outcome using the Timed Up and Go (TUG) test.. Of the 62 subjects enrolled, complete data were analyzed for 58 in Phase I and 54 participants in Phase II. Of those enrolled, most were African American (95%) and female (85%) and had multiple comorbidities and a mean age+/-standard deviation of 76.1+/-7.2. Mean baseline Hb was 10.5+/-0.9 g/dL (7.3-11.5). In Phase I, 67% of those taking epoetin alfa, and in Phase II, 69% of those taking epoetin alfa had an increase in Hb of more than 2 g/dL, significantly more than those taking placebo (P<.001). Similarly, elderly participants significantly improved on the fatigue and anemia subscales of the FACIT across phases (all P<.05). No significant differences were found between treatment and placebo on TUG scores. Epoetin alfa was well tolerated.. In this trial involving predominantly older African-American women with anemia, a direct relationship existed between increases in Hb during epoetin alfa therapy and improvements in fatigue and QOL.

Topics: Aged; Anemia; Chicago; Comorbidity; Cross-Over Studies; Double-Blind Method; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Mobility Limitation; Quality of Life; Recombinant Proteins; Treatment Outcome

C.E.R.A., a continuous erythropoietin receptor activator, is in development to provide anemia correction and stable maintenance of hemoglobin (Hb) levels at extended administration intervals in patients with chronic kidney disease (CKD). This study examined its efficacy and safety when administered up to once monthly in patients who have CKD and are on dialysis and randomly convert directly from epoetin alpha or beta one to three times weekly.. In this three-arm, comparator-controlled, open-label, randomized, parallel-group, Phase III study, 572 dialysis patients (> or =18 yr) who were receiving stable subcutaneous epoetin one to three times weekly were randomly assigned (1:1:1) to continue epoetin or to receive subcutaneous C.E.R.A. once monthly or twice monthly for 52 wk. Dosage was adjusted to maintain Hb +/-1.0 g/dl of baseline level. Primary end point was mean change in Hb level between baseline and the evaluation period (weeks 29 to 36).. Mean Hb levels during the evaluation period were similar between groups (once-monthly C.E.R.A. 11.5 g/dl; twice-monthly C.E.R.A. 11.7 g/dl; epoetin 11.5 g/dl). The difference between C.E.R.A. and epoetin in mean change (97.5% confidence interval) in Hb concentration between baseline and evaluation was -0.022 g/dl (-0.262 to 0.217) for once monthly and 0.141 g/dl (-0.098 to 0.380) for twice monthly. Analysis demonstrated that C.E.R.A. was as effective as epoetin in maintaining Hb and was well tolerated.. Subcutaneous C.E.R.A. once or twice monthly successfully maintained tight and stable Hb levels in patients who were on dialysis and randomly converted directly from epoetin one to three times weekly.

Topics: Anemia; Chronic Disease; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Diseases; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Renal Dialysis

Treatment of renal anaemia with epoetin is well established. However, epoetin is expensive. Biogeneric epoetin with proven efficacy would reduce cost and improve access to therapy. We conducted this first ever comparative study of a biogeneric and the original product.. Stable haemodialysis patients with haemoglobin (Hb) of at least 9 g/dL and receiving the human recombinant erythropoietin Eprex were randomized to continue Eprex or convert to GerEPO, a biogeneric epoetin, for 12 weeks. The primary efficacy variable was a change in Hb from baseline.. Ninety-three subjects were randomized to each arm. Ninety-two and 87 subjects on the Eprex and GerEPO arms, respectively, completed the trial. Mean Hb in both groups declined over time. The mean decline in Hb was -0.47 g/dL in the Eprex group and -0.45 g/dL in the GerEPO group. The mean difference in the change in Hb from baseline to week 12 between the two groups was 0.02. The 95% confidence interval was -0.42 to 0.46, which lies within the margin of equivalence (+/-0.5 g/dL). The results of intention-to-treat analysis were similar. There were no significant differences in the epoetin dose, iron therapy or iron stores between the groups. Patients receiving GerEPO reported more adverse events.. GerEPO was therapeutically equivalent to Eprex with respect to Hb response for patients with Hb in the subtherapeutic target range as is common in this study population. The trial duration was insufficient for safety evaluation, which must await further investigation. More biogeneric products should be subjected to rigorous evaluation.

Topics: Adult; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Iron; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Patients receiving chemotherapy for cancer often develop anemia, which can contribute to increased morbidity and reduced quality of life (QOL). Chemotherapy-induced anemia can be successfully treated using recombinant human erythropoietin (rHuEPO).. To demonstrate the effectiveness of once-weekly (QW) rHuEPO dosing to effect improved hemoglobin levels, decreased transfusion use, and improved functional outcomes and QOL in pediatric leukemic patients (ALL) receiving maintenance chemotherapy.. This was a prospective randomized, single-center, open-label, 12-week case-control study of epoetin alfa in pediatric patients with acute lymphoblastic leukemia (ALL) in remission receiving maintenance chemotherapy. Sixty patients were randomly assigned to receive either epoetin alfa (rHuEPO group = 30 cases, 17 males and 13 females, age; 6.8 +/- 2.33 years), or no epoetin alfa (control group = 30 cases, 16 males and 14 females, age; 6.76 +/- 2.28 years). Both groups were matched as regard age, sex, baseline Hb concentration, remission state, chemotherapy regimen, numbers and amount of blood transfusion, and leukemia state (both were low and standard risk). Epoetin alfa was administered at a dose of 450 IU/kg, once weekly, subcutaneously (s.c.) for 12 consecutive weeks. Endpoints were changes in hematologic and QOL parameters.. Among the 30 patients evaluable for hematologic response, the mean increase in Hb from baseline to time of final evaluation was 3.08 +/- 1.48 g/dl (p < 0.001). An increase in Hb of > or = 2 g/dl, in the absence of blood transfusion, occurred in 70% of patients (21 of 30 patients) who were on the study for > or = 30 days. The overall response rate (Hb increase > or = 2 g/dl or Hb > or = 12 g/dl in the absence of blood transfusion) was 90% (27 of 30 patients). In 30 patients who were evaluable for QOL assessment, epoetin-alpha therapy was found to significantly (p < 0.001) improve mean cancer linear analog scale (CLAS) scores for energy level, ability to perform daily activity, and overall QOL from baseline to the time of final evaluation. QW epoetin-alpha was found to be well tolerated.. Treatment with QW epoetin-alpha was found to increase Hb levels, decrease transfusion requirement, and improve functional status and QOL in anemic patients with ALL in maintenance receiving chemotherapy. The once-weekly schedule is convenient, safe, and may reduce the burden on patients, parents, and their caregivers by reducing the number of visits to the clinic.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Child; Child, Preschool; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Quality of Life; Recombinant Proteins; Remission Induction; Treatment Outcome

To evaluate the effect of epoetin alfa on quality of life (QOL) in patients with solid tumors and mild-to-moderate anemia receiving platinum-based chemotherapy relative to population norms.. In the original study, patients (n = 316) with hemoglobin (Hb) levels < or =12.1 g/dl were randomized 2:1 to receive either epoetin alfa at a dose of 10,000 U thrice weekly s.c. or best supportive care (BSC) to compare the effects on transfusion use, hematologic response, and QOL (measured by the Functional Assessment of Cancer Therapy-Anemia [FACT-An]and Cancer Linear Analogue Scale [CLAS]). The QOL data from this previously reported trial were reanalyzed here relative to population norms.. Mean baseline QOL scores were similar between groups. At study completion, mean CLAS, FACT-An, FACT-An Anemia subscale, and FACT-An Fatigue subscale scores were significantly higher for patients given epoetin alfa than for those treated with BSC. Compared with population norms, both groups had impaired QOL at baseline. Differences in mean QOL change scores from baseline to study end for epoetin alfa versus BSC were 3.17 points for the FACT-General Total, 9.90 for the FACT-An Fatigue subscale, and 7.30 for the FACT-An Anemia subscale. This was equivalent to corrections in QOL deficits attributable to epoetin alfa of 97.3%, 40.7%, and 38.0% for the FACT-General Total, FACT-An Fatigue, and FACT-An Anemia subscale scores, respectively, versus BSC. A somewhat greater QOL benefit was observed for the FACT-An Fatigue and FACT-An Anemia subscales in the subset of patients with baseline Hb levels >10.5 g/dl.. Patients in this study had impaired QOL compared with population norms. Early treatment with epoetin alfa to correct anemia improved QOL in a statistically significant and clinically meaningful way, and improvements were greater in patients with baseline Hb levels >10.5 g/dl.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Platinum Compounds; Quality of Life; Recombinant Proteins; Reference Values; Sickness Impact Profile; Treatment Outcome

This analysis of the results of a randomized, controlled trial evaluating the effects of epoetin alfa (EPO) therapy on transfusion requirements, hemoglobin (Hb), and quality of life (QOL) in patients with cancer receiving platinum-based chemotherapy was conducted to evaluate the effect of initial Hb level on study outcomes.. Patients with Hb levels < or =12.1 g/dl were randomized 2:1 to receive EPO, 10,000 U three times weekly s.c. or best supportive care (BSC) until 4 weeks after their last chemotherapy cycle. For this analysis, patients were stratified by baseline Hb level (< or =9.7 g/dl, >9.7 g/dl to < or =10.5 g/dl, >10.5 g/dl to < or =11.3 g/dl, and >11.3 g/dl to < or =12.1 g/dl), and study results were reanalyzed.. Significantly fewer EPO patients than BSC patients with initial Hb levels >9.7 g/dl to < or =12.1 g/dl required transfusions. EPO maintained Hb levels throughout the study for patients with Hb levels >11.3 g/dl to < or =12.1 g/dl, compared with a decrease with BSC. For patients with baseline Hb levels >10.5 g/dl, for whom the mean changes from baseline to last assessment were measured by the Cancer Linear Analogue Scale assessments of energy and overall QOL as well as by the Functional Assessment of Cancer Therapy (FACT)-Fatigue and FACT-An Anemia subscale, QOL scores were significantly greater with EPO than with BSC. QOL declined in patients receiving BSC, and the mean decreases in QOL scores were greater for BSC patients with baseline Hb levels >10.5 g/dl, compared with the overall BSC group.. In patients with cancer receiving platinum-based chemotherapy and with baseline Hb levels >10.5 g/dl, early intervention with EPO reduces transfusions, maintains Hb level, and maintains or improves QOL. This study supports the positive effects of early intervention when analyzed according to initial Hb value.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Platinum Compounds; Quality of Life; Recombinant Proteins; Sickness Impact Profile; Treatment Outcome

Epoetin alfa is an established treatment of anemia in patients with cancer who are receiving chemotherapy with or without radiation therapy. However, fewer data support its use in patients with cancer not currently receiving either therapy. This 16-week, open-label, nonrandomized, multicenter pilot study evaluated the clinical profile of epoetin alfa (40,000 U) administered weekly via subcutaneous injection in anemic patients with cancer not receiving chemotherapy or radiation therapy. The primary endpoint was the proportion of patients who achieved a minor (hemoglobin [Hgb] increase > or = 1-1.9 g/dL) or major (Hgb increase > or = 2 g/dL) hematologic response. The trial was temporarily suspended to amend the protocol to reflect updated package insert recommendations for target Hgb and dose adjustments. Of the 98 patients enrolled, 91 (mean age, 69.5 +/- 9.5 years; baseline Hgb level, 10.4 +/- 0.7 g/dL) were evaluated for efficacy in a modified intent-to-treat analysis. Nearly all patients (94.5% [86/91]) achieved a minor response, and the majority (80.2% [73/91]) achieved a major hematologic response at any time during the study. Mean Hgb levels increased steadily over the 12-week dosing period, with significant (P < 0.001) increases from baseline observed as early as week 2. Only one patient required a transfusion. Epoetin alfa was safe and well tolerated.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Pilot Projects; Recombinant Proteins

To describe the erythropoietin pharmacokinetic profile after once-weekly epoetin alfa treatment in critically ill patients. Secondary objectives were to compare pharmacodynamic and safety profiles between active treatment and placebo in these patients.. Randomized, double-blind, placebo-controlled study.. Medical, surgical, or mixed medical/surgical intensive care units.. A total of 73 anemic critically ill adults with an expected stay of >3 days and a hematocrit value of <38%.. Patients were randomized 2:1 to epoetin alfa, 40,000 IU, administered subcutaneously once weekly (n=48) or matching placebo (n=25) for up to 4 wks.. Serum erythropoietin concentration and hematologic variables (percentage reticulocytes [RETI], hemoglobin [Hb], and total red blood cell [RBC] counts) were measured, and area under the serum concentration-time curve from time 0 to the last blood sampling time at time t (t: 120, 144, or 168 hrs) postdose (AUC0-Tlast) for these three variables was determined. Mean serum erythropoietin concentrations in placebo patients were slightly higher than typical physiologic levels of erythropoietin in healthy subjects, although not appropriate for the degree of anemia in these patients. Overall, exposure of endogenous erythropoietin in the placebo group (in terms of AUC0-Tlast) was only about 20% of exposure to exogenous erythropoietin in the epoetin alfa group. Baseline hemoglobin levels were the same in both groups (9.9 g/dL). Mean change in hemoglobin level from baseline through day 29 was 1.9 g/dL and 1.6 g/dL in the epoetin alfa and placebo groups, respectively. Mean AUC(RETI)0-Tlast was higher with epoetin alfa than with placebo and was related to the AUC of erythropoietin. There were no apparent differences in AUC(Hb)0-Tlast and AUC(RBC)0-Tlast between epoetin alfa and placebo groups, which was most likely due to bleeding and transfusion events. Epoetin alfa was safe and well tolerated, with a rate of treatment-emergent complications similar to that seen with placebo.. Epoetin alfa, once weekly, augmented the erythropoietic response in critically ill patients as indicated by the increased erythropoietin levels and larger AUC(RETI)0-Tlast in treated patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Critical Illness; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Count; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Recombinant Proteins; Retrospective Studies; Treatment Outcome

This study is designed to assess the effect of early and complete correction of anemia by using recombinant human erythropoietin (epoetin) alfa on the progression of chronic kidney disease (CKD).. Patients were randomly assigned to achieve high (13 to 15 g/dL [130 to 150 g/L]) or low (11 to 12 g/dL [110 to 120 g/L]) hemoglobin-level targets during 4 months of stabilization, followed by 36 months of maintenance. Glomerular filtration rate (GFR) decrease was measured by using iohexol clearance. Quality of life, nutrition, and safety also were monitored.. Because of labeling changes for subcutaneous administration of epoetin alfa (Eprex; Johnson and Johnson, Schaffhausen, Switzerland), the study was terminated prematurely. There were 195 patients enrolled in each group; 108 high-hemoglobin and 133 low-hemoglobin patients entered the maintenance phase. Mean maintenance duration was 7.4 months for the high-hemoglobin group and 8.3 months for the low-hemoglobin group. GFR decrease was numerically, but not statistically significantly, lower with the high-hemoglobin group (0.058 versus 0.081 mL/min/1.73 m2/mo [< 0.01 mL/s/1.73 m2/mo]). Physical quality-of-life measures showed trends (Role-Physical, P = 0.055; Physical Function, P = 0.083) or statistically significant improvement (Vitality, P = 0.042) with high hemoglobin levels at the end of the stabilization phase. Adverse events were similar between groups. Cardiovascular adverse events occurred in 25% of the high-hemoglobin and 18% of the low-hemoglobin patients (P = 0.137). Neither epoetin dosage nor hemoglobin level was associated with cardiovascular adverse events or death.. These data suggest that normalization of hemoglobin levels in patients with CKD is safe. Longer duration studies are needed to clarify efficacy benefits with high hemoglobin levels.

Topics: Adolescent; Adult; Aged; Anemia; Chronic Disease; Disease Progression; Epoetin Alfa; Erythropoietin; Female; Glomerular Filtration Rate; Hematinics; Humans; Kidney Diseases; Male; Middle Aged; Quality of Life; Recombinant Proteins

A 16-week, open-label, multicentre, randomised trial of weekly epoetin alfa 40 000 units versus biweekly darbepoetin alfa 200microg among 358 patients with solid-tumour cancers and chemotherapy-induced anaemia demonstrated superior haematological outcomes with epoetin alfa. We sought to compare resource use, costs and clinical outcomes between treatment groups and report the results using a cost-consequences framework.. Pre-specified methods were used to assign costs (US dollars, year 2004-5 values) to medical resources and patient time using a societal perspective. Costs for inpatient care, outpatient care and physician services were based on US Medicare reimbursement rates. Indirect costs assigned to patient time spent receiving study medication were based on the mean hourly wage in the US. In the base-case analysis, the average wholesale price was used to assign costs to medications. Clinical outcomes included all haemoglobin levels and transfusions recorded throughout the trial. Sensitivity analyses were performed to evaluate the impact of different costing methods, cost sources, perspectives and methods to assign haemoglobin values following a blood transfusion.. Over a mean follow-up duration of 11.8 weeks, the average cost of study medications and their administration was the single largest component of total costs and was similar between groups (epoetin alfa 5979 US dollars and darbepoetin alfa 5935 US dollars, difference 44 US dollars; 95% CI -590, 692). There were no significant differences in the proportions of patients hospitalised (epoetin alfa 24.6%, darbepoetin alfa 22.0%; p = 0.57). Patients randomised to epoetin alfa experienced more inpatient days, on average, than patients randomised to darbepoetin alfa (2.6 vs 1.6, 95% CI for the difference, 0.07, 2.27). However, with regard to transfusions, patients in the epoetin alfa arm required fewer units of blood than patients in the darbepoetin alfa arm (0.46 vs 0.88, 95% CI for the difference -0.77, -0.08). Mean total costs, comprising costs for study medications and their administration, inpatient care, transfusions, unplanned radiation therapy, haematology and laboratory services, chemotherapy and non-chemotherapy drugs and indirect costs were 14,976 US dollars in the epoetin alfa arm compared with 14,101 US dollars in the darbepoetin alfa arm, a difference of 875 US dollars (95% CI for difference -849, 2607), of which 98% of the difference was attributable to higher inpatient costs in the epoetin alfa arm (2374 US dollars vs 1520 US dollars; 95% CI for difference -33, 1955). Assessments of multiple clinical measures demonstrated improved outcomes with epoetin alfa relative to darbepoetin alfa.. Most clinical outcome measures suggested greater improvement with epoetin alfa relative to darbepoetin alfa, but most costs for both agents appeared similar. Decision makers must evaluate the differences in costs and efficacy measures that are most relevant from their perspectives.

Topics: Adolescent; Adult; Anemia; Antineoplastic Agents; Blood Transfusion; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Fees, Medical; Female; Health Care Costs; Hematinics; Hematologic Tests; Hospitalization; Humans; Male; Middle Aged; Office Visits; Recombinant Proteins; Treatment Outcome; United States

Chemotherapy-induced anemia is widely treated in the United States with darbepoetin alfa (DA) or epoetin alfa (EA). This noninferiority study systematically compares efficacy and safety of DA and EA using common doses and schedules used in clinical practice.. Patients had a diagnosis of nonmyeloid malignancy with > or = 8 weeks of planned chemotherapy, age >or = 18 years, and anemia (hemoglobin < or = 11 g/dL). Patients were randomly assigned 1:1 to DA 200 microg every two weeks (Q2W) or EA 40,000 units every week (QW) for up to 16 weeks with identical dose adjustment rules. Efficacy was assessed by the incidence of RBC transfusion (Kaplan-Meier estimate). The definition of noninferiority was that the upper 95% CI limit of the observed difference in RBC transfusions between groups was less than 11.5%; this noninferiority margin was based on the treatment effect observed in placebo-controlled EA studies.. Of 1,220 patients randomly assigned, 1,209 received > or = one dose of the study drug. Common tumor types were lung (26%), breast (21%), and gastrointestinal (18%). Transfusion incidence from week 5 to the end of the treatment phase (the primary end point) was 21% in the DA group and 16% in the EA group; noninferiority was concluded because the upper 95% CI limit of the difference between groups (10.8%) was below the prespecified noninferiority margin. Sensitivity analyses using alternate statistical methods and analysis sets yielded similar results. Hemoglobin, quality of life, and safety end points further support equivalency of the erythropoietic therapies.. This large, phase III study demonstrates comparable efficacy of DA Q2W and EA QW. Less frequent dosing offers potential benefits for patients, caregivers and health care providers.

Topics: Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Treatment Outcome

In a previous study we showed that many patients with esophagogastric adenocarcinoma experience anemia during neoadjuvant chemotherapy. We now investigated the role of erythropoietin in managing anemia during neoadjuvant chemotherapy.. Patients with esophagogastric adenocarcinoma who experienced anemia (hemoglobin < 12 g/dL) during neoadjuvant treatment received erythropoietin 10,000 IE subcutaneously three times a week. Primary outcomes were the response to erythropoietin, safety, the need for allogeneic red blood cell transfusion, and the rate of postoperative complications.. Between April 2003 and December 2004, 24 patients (median age, 62 years) were enrolled. The mean hemoglobin level before chemotherapy was 12.5 g/dL and the mean hemoglobin level before patients received erythropoietin was 11.5 g/dL. One year after involvement in the trial, 4 of 17 analyzable patients were still anemic (hemoglobin level < 12 mg/dL). Twenty-two patients received erythropoietin, and 16 (73%) responded. We could observe a significant increase in hemoglobin concentrations under therapy with erythropoietin to 12.6 g/dL (p < 0.001). Two patients (8%) received allogeneic transfusions; the rate of postoperative complications was 16%. There were no erythropoietin-related adverse events.. Treatment with erythropoietin is effective and well tolerated in patients with esophagogastric adenocarcinoma who experience anemia during neoadjuvant chemotherapy.

Topics: Adenocarcinoma; Aged; Anastomosis, Surgical; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cisplatin; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Female; Fluorouracil; Gastrectomy; Hemoglobins; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Postoperative Complications; Prospective Studies; Recombinant Proteins; Stomach Neoplasms; Survival Analysis

This randomized, open-label, multicenter study compared the efficacy and safety of epoetin alfa (EPO) 80 000 U every 2 weeks (Q2W) to the FDA-approved regimen of 40 000 U weekly (QW) in patients with chemotherapy-induced anemia.. A total of 310 patients with nonmyeloid malignancy and baseline hemoglobin (Hb)

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins

Epoetin alpha is recombinant human erythropoietin with established efficacy and safety in the treatment of renal anemia. Epoetin omega is recombinant erythropoietin that differs from epoetin alpha in the sugar moiety. We compared the two epoetins in two 12-week efficacy studies (S1, S2) with twice-weekly dosing, and a single-dose crossover pharmacokinetic (PK) study in severely anemic hemodialysis patients. Epoetins were delivered subcutaneously in all studies. S1 was randomized (omega n = 39, alpha n = 38), while S2 included the patients from S1 (omega n = 32, alpha n = 24) with 'switched' treatments (omegaleft arrow over right arrowalpha). In the intent-to-treat analysis, average weekly difference in hemoglobin vs. the baseline value was higher in omega-treated patients in both studies: 1.94 +/- 0.81 vs. 1.23 +/- 0.62 g/dL in S1 and 1.44 +/- 0.72 vs. 0.95 +/- 0.62 g/dL in S2. The unadjusted and adjusted omega-alpha differences in S1 were 0.71 g/dL (95% CI 0.38-1.04; P < 0.001) and 0.78 g/dL (95% CI 0.49-1.08; P < 0.001), respectively. Differences in S2 were 0.48 g/dL (95% CI 0.11-0.86; P = 0.012) and 0.46 g/dL (95% CI 0.1-0.82; P = 0.025), unadjusted and adjusted, respectively. Average weekly epoetin dose was lower in the omega groups in both studies: 87 +/- 25 vs. 108 +/- 21 IU/kg in S1 and 106 +/- 25 vs. 125 +/- 20 IU/kg in S2. The unadjusted and adjusted omega-alpha differences in S1 were -21 IU/kg (95% CI -32 to -11; P < 0.001) and -24 IU/kg (95% CI -35 to -13; P < 0.001), respectively. Differences in S2 were -19 IU/kg (95% CI -31 to -6; P = 0.006) and -15 IU/kg (95% CI -28 to -2; P = 0.04), unadjusted and adjusted, respectively. In the PK study (n = 17), the peak and total exposure to epoetin after 50 IU/kg of either drug was approximately twice greater for epoetin omega: C(max) omega/alpha 2.19 (95% CI 1.55-3.11), AUC omega/alpha 2.24 (95% CI 1.64-3.06). Epoetins were comparably well tolerated. In hemodialysis patients, subcutaneous epoetin omega apparently provides greater bioavailability and anti-anemic effect per administered dose (IU) than epoetin alpha.

Topics: Anemia; Cross-Over Studies; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Chemotherapy-related anemia is prevalent among patients with hematologic malignancies. A randomized, open-label, multicenter trial of early versus late epoetin alfa in this population was conducted, focusing on quality of life (QOL).. Patients with non-Hodgkin lymphoma, Hodgkin lymphoma, chronic lymphocytic leukemia, or multiple myeloma and baseline hemoglobin of 10 to 12 g/dL who were scheduled for > or = 4 months of myelosuppressive chemotherapy were randomized to receive < or = 16 weeks of epoetin alfa at a dose of 40,000 U once weekly immediately (early) or to wait and only receive epoetin alfa if hemoglobin decreased to < 9 g/dL (late). Those patients with a hemoglobin level > 12 g/dL after 3 chemotherapy cycles were not randomized. The primary endpoint was a mean change in the Functional Assessment of Cancer Therapy-Anemia (FACT-An) total.. In all, 269 patients with a hemoglobin level < or = 12 g/dL were randomized. The mean total FACT-An increased 3.84 (95% confidence interval [95% CI], 0.21-7.46) in early patients and decreased 4.37 (95% CI, -7.99 to -0.74) in late patients (P = .003). Early patients had significantly (P < .05) higher mean scores for total FACT-General; FACT-General physical and functional well-being subscales, total anemia scale, and fatigue subscale; and daily activity, energy, and important activity Linear Analog Scale Assessment scales, as well as reduced bedrest days and restricted activity days. The mean hemoglobin increased 1.2 g/dL (95% CI, 0.98-1.46) in early patients but decreased 0.2 g/dL (95% CI, -0.32-0.12) in late patients (P < .0001). Adverse events were similar between groups (with fatigue being the most prevalent); clinically relevant thromboembolic events were more common in early patients.. Treating mild anemia immediately with epoetin alfa during chemotherapy for hematologic malignancy significantly improved QOL, productivity, and hemoglobin compared with delaying treatment until the hemoglobin level decreases to < 9.0 g/dL.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematologic Neoplasms; Hemoglobins; Humans; Male; Middle Aged; Quality of Life; Recombinant Proteins; Work Capacity Evaluation

This pilot study was conducted to evaluate the feasibility, activity, and safety of an induction dose of epoetin alpha in cancer patients with moderate or severe anemia who were receiving chemotherapy.. Thirty patients with solid tumors and hemoglobin (Hb) levels <11.0 g/dl were enrolled. Patients received single s.c. injections of epoetin alpha, 40 000 IU for three consecutive days, and were then observed for the following 30 days. The primary efficacy variable was the response rate (Hb increase > or=1 g/dl) at day 15. Secondary efficacy variables included the proportion of patients given blood transfusions between baseline and the end of study, the duration of response (Hb level > or=1 g/dl), and ability to maintain the planned chemotherapy dose (dose intensity).. At day 15, 23 of 30 (77%) patients had achieved increases in Hb levels of at least 1 g/dl. The mean Hb increase in responders was 2.0 g/dl [95% confidence interval (CI) = 1.7-2.3 g/dl]. The Hb increase was 2.3 +/- 0.7 g/dl in responders with baseline Hb levels <9.5 g/dl (median Hb value), and 1.7 +/- 0.6 g/dl in those with higher Hb levels (P = 0.012). The median duration of response was 6.1 weeks (95% CI = 1.6-10.6 weeks). Hematologic parameters were not significantly changed in nonresponders. Multivariate analysis detected no significant differences in Hb increase at day 15 on the basis of age, sex, weight, baseline Hb levels, type or stage of tumor, or treatment with platinum-based chemotherapy. No serious adverse event related to epoetin alpha treatment was observed.. We conclude that a higher initial dosing of epoetin alpha appears to be an efficient schedule for treating anemia in cancer patients undergoing chemotherapy, conferring higher response rates than those seen with standard doses. Further evaluation of these and other epoetin alpha dosage regimens is warranted.

Topics: Adult; Aged; Anemia; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematopoiesis; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins

The aim of the 18 months follow up study was to assess the frequency of anemia during IFN/RBV therapy in patients with chronic hepatitis C; to manage anemia either with recombinant human erythropoietin (rHuEPO)--epoetin alpha or with RBV dose reduction and to compare the rate of SVR in patients with RBV dose reduction and with administration of epoetin alpha. Study enrolled 61 patients with chronic active hepatitis C aged 33-61 years. All patients had HCV genotype 1b. Out of them 41 were male and 20 female. Anemia (Hb <10 or >2 g/dL Hgb drop from baseline) developed in 41 patients out of 61 (67,21%) during the therapy. These 41 patients were randomized into two groups: 21 patients who received 40 000 IU epoetin alpha weekly (I group) and 20 patients in whom for managing anemia we used standard of care (SOC) or RBV dose reductions from 1000/1200 to 800/600 mg (II group). In all 21 patients of the I group the Hb level normalized without reduction of RBV dose. In this group of patients SVR at 6 months after completion of full course of treatment was achieved in 17 (66%) patients. Improvement of quality of life (QOL) was observed in all 21 patients. Out of 20 patients of II group with standard of care (SOC) 5 patients developed symptomatic anemia with fatigue and dyspnoea; RBV was stopped temporarily. In 15 patients RBV dose was reduced from 1200 mg to 600 mg for correction of anemia. In this group of patients SVR at 6 months after treatment completion was achieved in 7 (25%) patients. Lower RBV doses yield a lower treatment response in patients with HCV genotype 1. In anemic HCV-infected patients on RBV/PEG-IFN therapy, EPO maintains RBV dose and significantly improves anemia and QOL. EPO has the potential to improve adherence rate, which may in turn improve SVR.

Topics: Adult; Anemia; Antiviral Agents; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Hepatitis C, Chronic; Humans; Interferons; Male; Middle Aged; Recombinant Proteins; Ribavirin; Treatment Outcome

Anemia, a common complication of chronic kidney disease, usually develops as a consequence of erythropoietin deficiency. Recombinant human erythropoietin (epoetin alfa) is indicated for the correction of anemia associated with this condition. However, the optimal level of hemoglobin correction is not defined.. In this open-label trial, we studied 1432 patients with chronic kidney disease, 715 of whom were randomly assigned to receive a dose of epoetin alfa targeted to achieve a hemoglobin level of 13.5 g per deciliter and 717 of whom were assigned to receive a dose targeted to achieve a level of 11.3 g per deciliter. The median study duration was 16 months. The primary end point was a composite of death, myocardial infarction, hospitalization for congestive heart failure (without renal replacement therapy), and stroke.. A total of 222 composite events occurred: 125 events in the high-hemoglobin group, as compared with 97 events in the low-hemoglobin group (hazard ratio, 1.34; 95% confidence interval, 1.03 to 1.74; P=0.03). There were 65 deaths (29.3%), 101 hospitalizations for congestive heart failure (45.5%), 25 myocardial infarctions (11.3%), and 23 strokes (10.4%). Seven patients (3.2%) were hospitalized for congestive heart failure and myocardial infarction combined, and one patient (0.5%) died after having a stroke. Improvements in the quality of life were similar in the two groups. More patients in the high-hemoglobin group had at least one serious adverse event.. The use of a target hemoglobin level of 13.5 g per deciliter (as compared with 11.3 g per deciliter) was associated with increased risk and no incremental improvement in the quality of life. (ClinicalTrials.gov number, NCT00211120 [ClinicalTrials.gov].).

Topics: Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Glomerular Filtration Rate; Heart Failure; Hematinics; Hemoglobins; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Recombinant Proteins; Renal Insufficiency, Chronic; Stroke; Survival Analysis

To demonstrate the efficacy and safety of epoetin delta for the treatment of anaemia in dialysis patients with chronic kidney disease (CKD).. This was a 12-week, randomized, double-blind, active-comparator study. CKD patients who were naïve to epoetin treatment and had haemoglobin < 10 g/dL were randomized to epoetin delta 15, 50, 150, or 300 IU/kg or epoetin alfa 50 IU/kg. Patients initially entered a correction phase until they recorded haemoglobin of > or = 11.5 g/dL for two consecutive weekly measurements or one haemoglobin measurement of > or = 13 g/dL (correction success). A maintenance phase followed where the dose was adjusted to maintain haemoglobin > or = 10.5 g/dL. Maintenance success was defined as haemoglobin > 10.5 g/dL at Week 12. Total success was defined as achieving maintenance and correction success.. The primary objective was to demonstrate that the proportion of patients achieving total success was greater in the pooled 150 IU/kg and 300 IU/kg groups compared with the 15 IU/kg dose group.. Total success was achieved in 55.6% of patients in the pooled highest epoetin delta group compared with 4.5% in the lowest dose group. There was no significant difference in total success for the epoetin delta and epoetin alfa 50 IU/kg groups. Significant increases in haemoglobin and haematocrit levels were observed in the 150 and 300 IU/kg dose groups. Adverse events occurred at frequencies expected for this patient group.. Epoetin delta was effective in increasing haemoglobin levels in patients with baseline haemoglobin of < 10 g/dL.

Topics: Adult; Aged; Anemia; Dose-Response Relationship, Drug; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Treatment Outcome

Results of treatment of 39 patients, to whom pancreatoduodenal resection was performed for periampullar zone tumour, were analyzed. Anemia, revealed before the operation, had constituted the factor, which trustworthily increased the postoperative complications occurrence risk. Therapeutic course, using recombinant erythropoietins, was conducted for correction of anemia in 7 patients. This had promoted the hemoglobin level raising, the risk of postoperative complications occurrence lowering, but did not influence the intraoperative blood loss severity and perioperative hemotransfusion volume.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anemia; Bile Duct Neoplasms; Digestive System Neoplasms; Drug Administration Schedule; Duodenal Neoplasms; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Recombinant Proteins; Risk Factors; Treatment Outcome

To determine whether weekly epoetin alfa could improve hemoglobin (HgB) levels, reduce RBC transfusions, and improve quality of life (QOL) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy.. This double-blind, placebo-controlled study randomly assigned patients to placebo or epoetin alfa (Ortho Biotech, Bridgewater, NJ) 40,000 U subcutaneous weekly for 16 weeks. QOL, HgB, and RBC transfusions were measured pretreatment and monthly.. The study accrued 344 patients; 330 were assessable for efficacy and 305 were assessable for QOL. Placebo-treated patients had a mean increase in HgB of 0.9 g/dL (range, -3.8 to +5.3) compared with 2.8 g/dL (range, -2.2 to +7.5) for epoetin-treated patients (P < .0001). During the study, 31.7% of placebo-treated patients achieved a > or = 2 g/dL HgB increase compared with 72.7% of epoetin-treated patients (P < .0001). The incidence of RBC transfusion for placebo and epoetin treatment arms was 39.6% and 25.3% (P = .005), respectively. The placebo group received 256 units of RBCs compared with 127 units in the epoetin group (P < .0001). The incidence of toxicity in the groups was similar. Changes in the average QOL scores from baseline to the end of the study were similar in the two groups (P = not significant). The HgB responders (irrespective of treatment arm) had a mean change in Functional Assessment of Cancer Therapy (FACT) fatigue score from a baseline of +5.1 compared with -2.1 for the nonresponders (P = .006).. Epoetin alfa significantly improved HgB and reduced transfusions in this patient population. These results support the use of weekly epoetin alfa as an ameliorative agent for cancer-related anemia.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Breast Neoplasms; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Injections, Subcutaneous; Lung Neoplasms; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Recombinant Proteins; Treatment Outcome

Epoetin alfa administered at 40,000 U once weekly (qw) to anemic cancer patients receiving chemotherapy increases hemoglobin levels, improves quality of life (QOL), and reduces transfusions. The benefit of epoetin alfa in maintaining hemoglobin levels in cancer patients with hemoglobin less than 12 g/dL has not been evaluated.. Breast cancer patients (N = 354) receiving chemotherapy were randomly assigned in 1:1 ratio to epoetin alfa (40,000 U qw) or standard of care (SOC). QOL was assessed at baseline and week 12. Hemoglobin responses, transfusion requirements, and prognostic factors for responses were measured.. At week 12, Functional Assessment of Cancer Therapy-Anemia (FACT-An; mean, 2.16 +/- 12.84 for epoetin alfa v -4.43 +/- 13.42 for SOC) and FACT-An fatigue (mean, 1.85 +/- 10.52 for epoetin alfa v -3.55 +/- 11.14 for SOC) change scores were significantly higher in the epoetin alfa group (P < .0001). Hemoglobin responses defined as mean hemoglobin > or = 12 g/dL or a > or = 2 g/dL increase compared with baseline were significantly higher in the epoetin alfa group versus SOC: 52.0% v 5.1% and 65.7% v 6.3%, respectively (P < .0001 for both comparisons). Percentage transfused was significantly lower in the epoetin alfa group compared with SOC (8.6% v 22.9%). More than 90% of patients did not require a dose increase and 28.7% had a dose reduction.. Epoetin alfa administered at 40,000 U qw is effective in improving QOL, maintaining hemoglobin level, and reducing transfusion requirements in breast cancer patients. The high effectiveness observed could be attributed in part to early treatment with epoetin alfa.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Middle Aged; Quality of Life; Recombinant Proteins; Treatment Outcome

This study evaluated the impact of a new epoetin alfa dosing regimen on quality of life (QOL), transfusion requirements, and hemoglobin (Hb) levels in 133 patients with low-risk myelodysplastic syndrome (MDS) and Hb < or =10 g/dl. Epoetin alfa 40,000 IU was given subcutaneously twice weekly; after 4 weeks, the dose could be reduced to 40,000 IU weekly in patients achieving erythroid response. QOL was assessed using the functional assessment of cancer therapy-anemia (FACT-An) questionnaire. FACT-An scores increased on average by 7.5 after 4 weeks and by 8.8 after 8 weeks compared with baseline. FACT-An scores were positively associated with Hb values (r=0.53, P<0.01). The mean FACT-An score increase at week 8 was 10.2 in responders and 5.6 in nonresponders. The overall erythroid response rate at week 8 was 68%: 74% in transfusion-independent patients and 59% in transfusion-dependent patients. Of all responders at week 8, response was maintained in 86% at week 12, 71% at week 16, 65% at week 20, and 54% at week 24. Treatment was generally well tolerated. Our data provide new and encouraging results regarding the benefits of 40,000 IU biweekly induction doses followed by 40,000 IU weekly in improving QOL, correcting anemia, and reducing transfusion requirements in low-risk MDS patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Quality of Life; Recombinant Proteins; Risk; Surveys and Questionnaires

The patterns of use and effectiveness of therapy with darbepoetin alfa and epoetin alfa for chemotherapy-induced anemia (CIA) in hospital outpatient and community settings were evaluated.. Data were collected from medical charts at 65 oncology clinics in hospital outpatient and community settings for consecutive patients who received the first dose of either darbepoetin alfa or epoetin alfa between August 1, 2002, and February 15, 2003, and were to have had 12 weeks of follow-up data.. Data from the charts of 3123 patients were abstracted. Of these patients, 2785 were treated with only one erythropoietic agent (1444 with darbepoetin alfa and 1341 with epoetin alfa) and were included in the analysis. The most common initial dosage of darbepoetin alfa was 200 microg every two weeks (61% of darbepoetin alfa recipients), and the most common initial dosage of epoetin alfa was 40,000 units weekly (72%). With these regimens, the dosage was escalated for 22% of darbepoetin alfa recipients and 23% of epoetin alfa recipients at a median of six weeks after the initial dose. The mean change from baseline in hemoglobin concentration after 12 weeks of therapy was similar for both groups, as was the percent of patients with red-blood-cell transfusions during treatment.. The most common initial dosage of darbepoetin alfa for CIA was 200 microg every two weeks, and the most common initial dosage of epoetin alfa was 40,000 units weekly. At these dosages, the two agents appear to have similar clinical effectiveness.

Topics: Aged; Anemia; Antineoplastic Agents; Cohort Studies; Darbepoetin alfa; Data Collection; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Outpatients; Recombinant Proteins; Retrospective Studies; Time Factors; Treatment Outcome

This prospective, open-label, multicenter study was undertaken to determine the safety and efficacy of epoetin alfa in increasing hemoglobin levels and improving quality of life (QOL), specifically fatigue, in cancer patients receiving chemotherapy with or without radiotherapy (n=702). Epoetin alfa, 10,000 IU three times a week s.c. for 8-18 weeks, increased the mean hemoglobin level relative to baseline (1.0 +/- 1.5 g/dl by week 4 and > or =1.7 g/dl from week 10 through the end of the trial), with 63.4% of patients experiencing > or =2 g/dl increases in hemoglobin above baseline at some time during the study. Fatigue is an important component of QOL. Physicians, nurses, and patients independently assessed patient fatigue level on a linear-analogue scale. Although all three groups reported improvements in patient fatigue over the course of the study (p <.0001), the magnitude of fatigue ratings and their relationship to tumor response and to hemoglobin level varied by group. Overall, epoetin alfa was well tolerated and effective in improving hemoglobin levels and decreasing fatigue in patients undergoing chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Treatment Outcome

Preoperative epoetin alfa administration decreases transfusion requirements and may reduce transfusion complications, such as postoperative infection due to immune suppression and thus hospitalization time. This study examined the impact of preoperative epoetin alfa administration on postoperative recovery and infection rate.. In an open randomized controlled multicentre trial in patients undergoing orthopaedic surgery, the effects of preoperative administration of epoetin alfa vs. routine care were compared in six countries. Haemoglobin (Hb) values, transfusions, time to ambulation, time to discharge, infections and safety were evaluated in patients with preoperative Hb concentrations 10-13g dL(-1) (on-treatment population: epoetin n = 460; control n = 235), from study entry until 4-6 weeks after surgery. Outcome was also compared in patients with and without transfusion.. Epoetin-treated patients had higher Hb values from the day of surgery until discharge (P < 0.001) and lower transfusion rates (12% vs. 46%; P < 0.001). Epoetin treatment delivered no significant effect on postoperative recovery (time to ambulation, time to discharge and infection rate). However, the time to ambulation (3.8+/-4.0 vs. 3.1+/-2.2days; P < 0.001)and the time to discharge (12.9+/-6.4 vs. 10.2+/-5.0 days; P < 0.001) was longer in the transfused than in the non-transfused patients. Side-effects in both groups were comparable.. Epoetin alfa increases perioperative Hb concentration in mild-to-moderately anaemic patients and thus reduces transfusion requirements. Patients receiving blood transfusions require a longer hospitalization than non-transfused patients.

Topics: Aged; Anemia; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Transfusion; Epoetin Alfa; Erythropoietin; Europe; Female; Hematinics; Hemoglobins; Humans; Male; Orthopedic Procedures; Postoperative Care; Postoperative Complications; Prospective Studies; Recombinant Proteins; Surgical Wound Infection; Treatment Outcome

It is unclear whether physiologic hemoglobin targets lead to cardiac benefit in incident hemodialysis patients without symptomatic heart disease and left ventricular dilation. In this randomized, double-blind study, lower (9.5 to 11.5 g/dl) and higher (13.5 to 14.5 g/dl) hemoglobin targets were generated with epoetin alpha over 24 wk and maintained for an additional 72 wk. Major eligibility criteria included recent hemodialysis initiation and absence of symptomatic cardiac disease and left ventricular dilation. The primary outcome measure was left ventricular volume index (LVVI). The study enrolled 596 patients. Mean age, duration of dialysis therapy, baseline predialysis hemoglobin, and LVVI were 50.8 yr, 0.8 yr, 11.0 g/dl, and 69 ml/m2, respectively; 18% had diabetic nephropathy. Mean hemoglobin levels in the higher and lower target groups were 13.3 and 10.9 g/dl, respectively, at 24 wk. Percentage changes in LVVI between baseline and last value were similar (7.6% in the higher and 8.3% in the lower target group) as were the changes in left ventricular mass index (16.8 versus 14.2%). For the secondary outcomes, the only between-group difference was an improved SF-36 Vitality score in the higher versus the lower target group (1.21 versus -2.31; P = 0.036). Overall adverse event rates were similar in both target groups; higher (P < 0.05) rates of skeletal pain, surgery, and dizziness were seen in the lower target group, and headache and cerebrovascular events were seen in the higher target group. Normalization of hemoglobin in incident hemodialysis patients does not have a beneficial effect on cardiac structure, compared with partial correction.

Topics: Adult; Aged; Anemia; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Heart Diseases; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Recombinant human erythropoietin (EPO) is used for the treatment of last stage renal anemia. A new EPO preparation was obtained in Cuba in order to make this treatment fully nationally available. The aim of this study was to compare the pharmacokinetic, pharmacodynamic and safety properties of two recombinant EPO formulations in patients with anemia due to end-stage renal disease on hemodialysis.. A parallel, randomized, double blind study was performed. A single 100 IU/Kg EPO dose was administered subcutaneously. Heberitro (Heber Biotec, Havana, formulation A), a newly developed product and Eprex (CILAG AG, Switzerland, formulation B), as reference treatment were compared. Thirty-four patients with anemia due to end-stage renal disease on hemodialysis were included. Patients had not received EPO previously. Serum EPO level was measured by enzyme immunoassay (EIA) during 120 hours after administration. Clinical and laboratory variables were determined as pharmacodynamic and safety criteria until 216 hours.. Both groups of patients were similar regarding all demographic and baseline characteristics. EPO kinetics profiles were similar for both formulations; the pharmacokinetic parameters were very close (i.e., AUC: 4667 vs. 4918 mIU.h/mL; Cmax: 119.1 vs. 119.7 mIU/mL; Tmax: 13.9 vs. 18.1 h; half-life, 20.0 vs. 22.5 h for formulations A and B, respectively). The 90% confidence intervals for the ratio between both products regarding these metrics were close to the 0.8-1.25 range, considered necessary for bioequivalence. Differences did not reach 20% in any case and were not determined by a formulation effect, but probably by a patients' variability effect. Concerning pharmacodynamic features, a high similitude in reticulocyte counts increments until 216 hours and the percentage decrease in serum iron until 120 hours was observed. There were no differences between formulations regarding the adverse events and their intensity. The more frequent events were pain at injection site (35.3%) and hypertension (29%). Additionally, further treatment of the patients with the study product yielded satisfactory increases in hemoglobin and hematocrit values.. The formulations are comparable. The newly developed product should be acceptable for long-term application.

Topics: Adult; Aged; Anemia; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Treatment Outcome

This work was conducted to evaluate the effect of early intervention with epoetin alfa (EPO) on transfusion requirements, hemoglobin level (Hb), quality of life (QOL) and to explore a possible relationship between the use of EPO and survival, in patients with solid tumors receiving platinum-based chemotherapy. Three hundred and sixteen patients with Hb12.1g/dL were randomised 2:1 to EPO 10000 IU thrice weekly subcutaneously (n = 211) or best supportive care (BSC) (n = 105). The primary end point was proportion of patients transfused while secondary end points were changes in Hb and QOL. The protocol was amended before the first patient was recruited to also prospectively collect survival data. EPO therapy significantly decreased transfusion requirements (P < 0.001) and increased Hb (P < 0.005). EPO-treated patients had significantly improved QOL compared with BSC patients (P < 0.05). Kaplan-Meier estimates showed no differences in 12-month survival (P = 0.39), despite a significantly greater number of patients with metastatic disease in the EPO group (78% vs. 61%, P = 0.001). EPO was well tolerated. This study has shown that early intervention with EPO can result in a significant reduction of transfusion requirements and increases in Hb and QOL in patients with mild anemia during platinum-based chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Platinum; Quality of Life; Recombinant Proteins; Survival Analysis

Fatigue can be a major problem for cancer patients receiving chemotherapy, and anaemia is known to be an important contributory factor. Several studies have shown that treatment with epoetin alfa raises haemoglobin levels, reduces fatigue and improves health-related quality of life (HrQoL). However, it is often difficult for clinicians to relate reported HrQoL improvements from clinical trials to meaningful benefits for their patients. Results from a large-scale, placebo-controlled study were used to determine the minimally important difference in HrQoL, defined as the 'smallest difference in score...which patients perceive as beneficial and which would mandate...a change in the patient's management'. This analysis confirmed that, for the five QoL scales used, epoetin alfa conferred not only a statistically significant but also a clinically significant benefit in terms of QoL compared to placebo, since, in each case, the benefit associated with epoetin alfa use was considerably higher than the minimally important difference.

Topics: Adult; Anemia; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoietin; Fatigue; Female; Humans; Male; Neoplasms; Placebos; Quality of Life; Recombinant Proteins

Incomplete data are inevitable in quality-of-life (QoL) studies involving cancer patients, since a proportion of patients will not complete the trial. Traditional analyses assume that such data are missing at random, but this assumption may be incorrect. We therefore applied mixed-effects statistical models to determine the effects of non-random missing data. Models were applied to results from a large-scale, randomised study of epoetin alfa versus placebo in 375 patients receiving non-platinum-based chemotherapy. The model suggested that QoL data were not missing at random and that analyses based on an assumption of random missing data gave an over-optimistic impression of QoL changes within treatment groups. However, sensitivity analysis demonstrated that the effectiveness of treatment with epoetin alfa compared to placebo in terms of QoL benefits remained highly significant, confirming the original conclusions of the study.

Topics: Anemia; Antineoplastic Agents; Data Collection; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Neoplasms; Placebos; Quality of Life; Recombinant Proteins

Anaemia is an important factor in the fatigue experienced by many patients receiving chemotherapy. A recent large-scale, randomised, placebo-controlled trial has shown that treatment with epoetin alfa raises haemoglobin levels, reduces fatigue and improves overall quality of life (QoL). In order to examine the relationship between anaemia and QoL more closely, we performed multiple regression analyses, adjusting for possible differences in demographic and clinical characteristics between the treatment groups on the trial data derived from FACT, CLAS and SF-36 QoL assessments. This confirmed that QoL is correlated with haemoglobin levels and that treatment with epoetin alfa is associated with a significant improvement in QoL as measured by validated cancer-specific instruments such as FACT and CLAS. However, the sub-group of patients who suffer disease progression during treatment are not predicted to experience an improvement in QoL, confirming the sensitivity of these scales. Race and tumour type were significantly related to changes in QoL scores, but other factors such as age and gender did not show significant effects on QoL.

Topics: Anemia; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Humans; Linear Models; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Recombinant Proteins

Anaemia is a common problem for cancer patients and often causes fatigue and reduces quality of life (QoL). Although randomised trials have repeatedly shown that treatment with epoetin alfa raises haemoglobin levels, reduces fatigue and improves overall QoL, such findings may be hard to put into a clinical context and, as a result, cancer-related fatigue remains undertreated. This study gathered data using the FACT-An QoL scale from 1400 people on an internet survey panel. The 1400 were randomly selected and chosen to be representative of the total US population. Survey results were then compared with the findings from a large placebo-controlled study involving 375 anaemic cancer patients. FACT-An showed good psychometric properties in the survey population and was able to distinguish respondents with histories of anaemia and cancer from those without. Comparing the population norm values for FACT-An with the trial data showed that treatment with epoetin alfa led to clinically meaningful improvements in cancer patients' QoL.

Topics: Anemia; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Humans; Linear Models; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Recombinant Proteins; Surveys and Questionnaires

Recombinant human erythropoietin (epoetin alfa) is an effective treatment for anaemia in cancer patients, and over two-thirds of recipients experience a substantial increase in haemoglobin concentration (>2 g/dl). However, it would be helpful to identify responders before starting treatment. Some studies have suggested that high pre-treatment levels of endogenous erythropoietin pre-treatment levels of endogenous erythropoietin or other pre-treatment or early response variables are associated with a poor response to epoetin alfa, and several predictive algorithms have been published. We analysed data pooled from 9 clinical trials of 1010 patients to determine the clinical usefulness of pre-treatment erythropoietin levels and other variables for predicting response. This showed that pre-treatment factors alone do not provide a clinically useful prediction of response. The sensitivity of these models increases slightly if early response variables, such as the change in haemoglobin after 4 weeks, are included, but specificity remains poor. We conclude that, while there may be a statistical relationship between certain factors and response, none approach clinically useful levels of sensitivity or specificity.

Topics: Anemia; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoietin; Factor Analysis, Statistical; Female; Humans; Male; Middle Aged; Neoplasms; Placebos; Recombinant Proteins

Anemia, fatigue, and diminished quality of life (QOL) often are associated with chemotherapy. In a previous study of patients with early-stage breast cancer and a mean baseline hemoglobin (Hb) level of 12.1 g/dL, Hb decreased by 2.0 g/dL after 4 cycles of adjuvant chemotherapy. The current open-label, nonrandomized, multicenter, prospective, community-based study evaluated the effects of 12-24 weeks of epoetin alfa (40,000 U subcutaneously once weekly initiated at the start of standard adjuvant chemotherapy) in patients with stage I-III breast cancer and baseline Hb levels > or =10 g/dL to < or =14 g/dL on Hb level, transfusions, and QOL.. Of 1792 patients enrolled, 1785 were evaluable for safety and 1632 for efficacy. Mean age was 53 years +/- 10.7 and mean baseline Hb level was 12.3 g/dL +/- 1.0. From baseline levels, epoetin alfa significantly increased Hb (1.3 g/dL +/- 1.5; P < 0.05) and improved QOL according to the Linear Analog Scale Assessment (LASA) of energy (5.1 mm +/- 27.7), LASA activity (5.1 mm +/- 28.2), LASA overall QOL (4.3 mm +/- 26.7), and Functional Assessment of Cancer Therapy-Anemia (1.7 points +/- 14.0; P < 0.05 in each case). Patients with baseline mild anemia (Hb level >10 g/dL to < or =12 g/dL) also had significant improvements from baseline levels in all 3 LASA parameters (P < 0.05). Epoetin alfa was well tolerated; clinically relevant thrombovascular events were reported in 4.3% of patients.. In this study, epoetin alfa significantly improved Hb and QOL in mildly anemic patients with early-stage breast cancer receiving adjuvant chemotherapy. However, based on recent studies showing an increased risk of thrombovascular events in patients with cancer treated with erythropoietic agents beyond correction of anemia, treatment with epoetin alfa is not indicated or recommended in patients with cancer and Hb levels > 12 g/dL.. Controlled studies are warranted to confirm the safety and efficacy of epoetin alfa therapy in patients with mild anemia receiving chemotherapy.

Topics: Adult; Anemia; Breast Neoplasms; Chemotherapy, Adjuvant; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Middle Aged; Prospective Studies; Quality of Life; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

Topics: Adolescent; Adult; Aged; Anemia; Antiviral Agents; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hepatitis C; HIV Infections; Humans; Interferons; Male; Middle Aged; Quality of Life; Recombinant Proteins; Ribavirin

The purpose of this study was to compare erythropoietin dosage requirements during subcutaneous versus intravenous administration in a hemodialysis population. Hemodialysis patients receiving subcutaneous epoetin alfa were switched to the intravenous route using a prospective, crossover design. Baseline anemia parameters were measured at months -2, -1, and 0 when patients were receiving subcutaneous dosing and compared to months 4, 5, and 6 after the switch to intravenous dosing. Ninety-eight patients were enrolled into the study with an average age of 54.8 years. Over the course of the study, 34 patients were excluded from analysis, leaving 64 patients with complete hemoglobin and erythropoietin dosing data throughout the subcutaneous and intravenous evaluation periods. In these patients, the dose of erythropoietin increased significantly from the subcutaneous to the intravenous period (7567.7 to 10229.2 IU/wk). The conversion of hemodialysis patients from the subcutaneous to the intravenous route of administration significantly increased epoetin alfa dosage requirements.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Cross-Over Studies; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

Colorectal cancer patients are often anemic before surgery, and this leads to an increased requirement for allogeneic blood transfusion. This may result in transfusion-induced immunosuppression, which in turn leads to increased morbidity and possibly an increased rate of tumor relapse. We investigated the possible benefits of perioperative epoetin alfa administration in anemic patients to correct hemoglobin levels and reduce transfusion needs.. A total of 223 colorectal cancer patients with anemia scheduled for surgery were randomized to a group that received epoetin alfa 150 or 300 IU/kg/day subcutaneously for 12 days (day -10 to +1) or to a control group. All received iron (200 mg/day by mouth) for 10 days before surgery. Hemoglobin levels, hematocrit, and the number of blood units transfused were recorded.. A total of 204 patients were eligible for analysis. Mean hemoglobin levels and hematocrit were significantly higher in the 300 IU/kg group than in the control group, both 1 day before surgery (hemoglobin, P = .008; hematocrit, P = .0005) and 1 day after surgery (hemoglobin, P = .011; hematocrit, P = .0008). Blood loss during and after surgery was similar in all groups. Patients who received epoetin alfa 300 IU/kg required significantly fewer perioperative transfusion units than control patients (.81 vs. 1.32; P = .016) and significantly fewer postoperative units (.87 vs. 1.33; P = .023). There were no significant differences in the number of units in the 150 IU/kg group.. Preoperative epoetin alfa (300 IU/day) increases hemoglobin levels and hematocrit in colorectal surgery patients. These effects are associated with a reduced need for perioperative and postoperative transfusions.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Colectomy; Colorectal Neoplasms; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematologic Tests; Humans; Male; Middle Aged; Preoperative Care; Recombinant Proteins

To evaluate the effect on survival and quality of life of maintaining hemoglobin (Hb) in the range of 12 to 14 g/dL with epoetin alfa versus placebo in women with metastatic breast cancer (MBC) receiving first-line chemotherapy.. Eligible patients were randomly assigned to receive epoetin alfa 40,000 U once weekly or placebo for 12 months. Study drug was initiated if baseline Hb was < or = 13 g/dL or when Hb decreased to < or = 13g/dL during the study. The primary end point was 12-month overall survival (OS).. The study drug administration was stopped early in accordance with a recommendation from the Independent Data Monitoring Committee because of higher mortality in the group treated with epoetin alfa. Enrollment had been completed, with 939 patients enrolled (epoetin alfa, n = 469; placebo, n = 470). Most patients had Hb more than 12 g/dL at baseline (median Hb, 12.8 g/dL) or during the study. From the final analysis, 12-month OS was 70% for epoetin alfa recipients and 76% for placebo recipients (P = .01). Optimal tumor response and time to disease progression were similar between groups. The reason for the difference in mortality between groups could not be determined from additional subsequent analyses involving both study data and chart review.. In this trial, the use of epoetin alfa to maintain high Hb targets in women with MBC, most of whom did not have anemia at the start of treatment, was associated with decreased survival. Additional research is required to clarify the potential impact of erythropoietic agents on survival when the Hb target range is 10 to 12 g/dL.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Middle Aged; Neoplasm Metastasis; Placebos; Quality of Life; Recombinant Proteins; Survival Analysis

To determine whether extended epoetin alfa dosing schedules of up to once every four weeks are as effective as weekly dosing in maintaining hemoglobin (Hb) levels in patients with anemia of chronic kidney disease (CKD).. This randomized, open-label trial enrolled patients with anemia of CKD not on dialysis. Patients were required to have a stable Hb level (> or = 11.0 g/dl) and to have been previously receiving epoetin alfa for two or more months. Patients were randomized to one of four subcutaneously administered epoetin alfa dosing regimens: 10,000 units (U) once weekly (QW), 20,000 U every two weeks (Q2W), 30,000 U every three weeks (Q3W) or 40,000 U every four weeks (Q4W). Dose reductions, but not escalations, were permitted. Patients received treatment for a total of 16 weeks. The primary endpoint for the trial was the mean final Hb measurements of the QW, Q2W, Q3W, and Q4W groups. The primary efficacy analyses were non-inferiority assessments of the mean final Hb measurements of the Q2W, Q3W, and Q4W groups, compared with the QW group. The primary efficacy analyses were performed using a modified intent-to-treat (MITT) population, defined as all patients meeting all inclusion/exclusion criteria (or, if not satisfying all criteria, were granted an exemption at study entry), and who were randomized and received at least one dose of study medication. A per-protocol population, based on all patients who met the MITT criteria and completed the entire study, was used to evaluate the robustness of the MITT results. Quality of life was assessed for all dosing groups throughout the study. Safety was based on all patients randomized who received at least one dose of study medication.. A total of 519 patients were enrolled; 445 were included in the MITT population. The four treatment groups were comparable with respect to baseline characteristics. The primary etiologies of CKD were diabetes (45.7%) and hypertension (29.9%). The mean baseline Hb, serum creatinine and glomerular filtration rate for all patients were 11.9 +/- 0.8 g/dl, 3.1 mg/dl, and 21.1 ml/min/1.73 m2, respectively. The mean baseline transferrin saturation was 25.2% and the mean ferritin was 201.9 ng/ml for all patients. All groups had a mean final Hb of > 11.0 g/dl. The mean final Hb levels of the Q2W and Q4W groups were statistically non-inferior to the QW group. The results of the per-protocol analysis were consistent with the MITT results. In addition, 93.5%, 89.5%, 77.2%, and 76.0% of patients maintained a mean Hb > or = 11.0 g/dl throughout the course of the study in the QW, Q2W, Q3W, and Q4W groups, respectively. Quality of life was maintained or improved from baseline to final within each dosing group. There were no significant differences in the mean final quality of life scores between the QW group and the Q2W, Q3W, and Q4W groups. Among the 513 patients evaluated for safety, epoetin alfa was well tolerated with no differences in adverse events between groups. The incidence of thrombotic adverse events was low (2.5% of patients), as was mortality (1.4% of patients).. Approximately 90% of patients dosed once every two weeks and over 75% of patients dosed once every three or four weeks maintained mean Hb levels > or = 11.0 g/dl, consistent with the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. This study suggests that extended epoetin alfa dosing schedules are effective and safe for maintaining Hb, and may offer the possibility of increased flexibility and convenience for the majority of patients with the anemia of CKD.

Topics: Aged; Analysis of Variance; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Quality of Life; Recombinant Proteins; Treatment Outcome

This is the first randomized, open-label, multicenter trial designed and powered to directly compare the hemoglobin (Hb) response to epoetin alfa (EPO), 40,000 U once weekly (QW), with that to darbepoetin alfa (DARB), 200 microg every 2 weeks (Q2W), in anemic patients with cancer receiving chemotherapy (CT). Transfusion requirements, quality of life (QOL), and safety also were evaluated. Adults with solid tumors scheduled to receive CT for > or =12 weeks and with baseline Hb < or =11 g/dl were randomized to receive either EPO 40,000 U QW (n = 178) or DARB 200 microg Q2W (n = 180) s.c. for up to 16 weeks. Doses were increased for nonresponders (Hb increase <1 g/dl) after 4 (EPO) or 6 (DARB) weeks, as per National Comprehensive Cancer Network guidelines, and were reduced for a rapid rise in Hb (>1.3 g/dl [EPO] or >1.0 g/dl [DARB] within any 2-week period) or for an Hb level >13 g/dl. The proportion of patients achieving a > or =1-g/dl Hb rise by week 5, the primary end point, was significantly higher with EPO (47.0%) than with DARB (32.5%), and EPO-treated patients achieved a > or =1-g/dl Hb increase significantly earlier than those receiving DARB (median, 35 days versus 46 days). The mean increase in Hb from baseline was significantly higher at weeks 5, 9, 13, and the end of the study with EPO than with DARB. The number of units transfused per patient was significantly lower for the EPO group than for the DARB group. The proportions of patients requiring transfusions, mean QOL improvements, and tolerability profiles were similar in the two groups.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins

Of the known risk factors for chronic kidney disease (CKD), race represents one that is non-modifiable, while smoking is another that is modifiable. Moreover, smoking tends to increase red blood cell mass, which is frequently diminished in CKD. No studies have examined the interplay of race with smoking on anaemia management in patients with CKD.. We examined the effects of smoking on anaemia management in CKD and its variation across race in a previously conducted study of CKD patients (n = 1312) initiated on weekly epoetin alfa and followed for 16 weeks. Smoking status was classified as current vs non-smoker. Race was classified as African-American vs non-African-American. Changes in estimated glomerular filtration rate, urinary albumin excretion, and erythropoietic response to weekly epoetin alfa were examined.. Overall, African-Americans had lower baseline Hb than non-African-Americans. African-American non-smokers did not mount an erythropoetic response comparable to other non-smokers by final Hb (mean 11.29 g/dl vs 11.64 g/dl, P<0.001) or week 16 Hb (mean 11.61 g/dl vs 11.86 g/dl, P = 0.02). However, African-American smokers had a more significant erythropoietic response than their non-smoking counterparts and were comparable to their smoking non-African-American counterparts. There was no effect of smoking on renal function or urinary protein excretion over the course of the study.. African-American non-smokers exhibit a diminished response to standard epoetin alfa dosing than non-smokers in other races. However, African-American smokers with CKD exhibit a response to epoetin alfa comparable to patients of other races. These findings may have implications for African-Americans who have CKD-related anaemia.

Topics: Aged; Anemia; Black or African American; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferritins; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Risk Factors; Smoking; Treatment Outcome; United States

To examine associations between early hemoglobin response and alternative measures of efficacy following treatment with an erythropoietic agent for chemotherapy-related anemia.. Preliminary data from an ongoing randomized, multicenter, 16-week, open-label clinical trial of epoetin alfa versus darbepoetin alfa were used to dichotomize patients based on attainment of early hemoglobin response (> or = 1 g/dL increase in hemoglobin level within 4 weeks of treatment initiation). Measures of efficacy were compared between patients with early hemoglobin response and those without. Sensitivity analyses were then performed to evaluate the impact of various methods for handling censored data and hemoglobin values following blood transfusion.. Efficacy measures included: the proportion of patients with a > or = 1 g/dL increase in hemoglobin by 4 weeks or a > or = 2 g/dL increase by 8 weeks; mean hemoglobin levels at 4, 8, 12, and 16 weeks; area under the curve for change in hemoglobin level; proportion of patients who required a blood transfusion after 4 weeks; proportion of follow-up days on which patients had hemoglobin levels within the therapeutic range of 11 g/dL to 13 g/dL; and proportion of patients who never had a hemoglobin level within this range.. A total of 274 patients were included (66.1% female, mean age 62.4), of whom 48.9% had an early hemoglobin response and 51.1% did not. Mean duration of follow-up was 10.1 +/- 5.05 weeks. All metrics indicated superior longer-term response among patients with early hemoglobin response compared to patients without early response. The findings were robust across sensitivity analyses. Although the analysis establishes a significant relationship between early hemoglobin response and alternative efficacy metrics, causality cannot be inferred.. Early hemoglobin response is significantly associated with various metrics of clinical response to erythropoietic agents and is an appropriate measure for evaluating treatment effects.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Sensitivity and Specificity; Treatment Outcome

This randomized clinical trial is designed to assess whether the prevention and/or correction of anemia, by immediate versus delayed treatment with erythropoietin alfa in patients with chronic kidney disease, would delay left ventricular (LV) growth. Study design and sample size calculations were based on previously published Canadian data.. One hundred seventy-two patients were randomly assigned. The treatment group received therapy with erythropoietin alfa subcutaneously to maintain or achieve hemoglobin (Hgb) level targets of 12.0 to 14.0 g/dL (120 to 140 g/L). The control/delayed treatment group had Hgb levels of 9.0 +/- 0.5 g/dL (90 +/- 5 g/L) before therapy was started: target level was 9.0 to 10.5 g/dL (90 to 105 g/L). Optimal blood pressure and parathyroid hormone, calcium, and phosphate level targets were prescribed; all patients were iron replete. The primary end point is LV growth at 24 months.. One hundred fifty-two patients were eligible for the intention-to-treat analysis: mean age was 57 years, 30% were women, 38% had diabetes, and median glomerular filtration rate was 29 mL/min (0.48 mL/s; range, 12 to 55 mL/min [0.20 to 0.92 mL/s]). Blood pressure and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were similar in the control/delayed treatment and treatment groups at baseline. Erythropoietin therapy was administered to 77 of 78 patients in the treatment group, with a median final dose of 2,000 IU/wk. Sixteen patients in the control/delayed treatment group were administered erythropoietin at a median final dose of 3,000 IU/wk. There was no statistically significant difference between groups for the primary outcome of mean change in LV mass index (LVMI) from baseline to 24 months, which was 5.21 +/- 30.3 g/m2 in the control/delayed treatment group versus 0.37 +/- 25.0 g/m2 in the treatment group. Absolute mean difference between groups was 4.85 g/m2 (95% confidence interval, -4.0 to 13.7; P = 0.28). Mean Hgb level was greater in the treatment group throughout the study and at study end was 12.75 g/dL (127.5 g/L in treatment group versus 11.46 g/dL [114.6 g/L] in control/delayed treatment group; P = 0.0001). LV growth occurred in 20.1% in the treatment group versus 31% in the control/delayed treatment group (P = 0.136). In patients with a stable Hgb level, mean LVMI did not change (-0.25 +/- 26.7 g/m2), but it increased in those with decreasing Hgb levels (19.3 +/- 28.2 g/m2; P = 0.002).. This trial describes disparity between observational and randomized controlled trial data: observed and randomly assigned Hgb level and LVMI are not linked; thus, there is strong evidence that the association between Hgb level and LVMI likely is not causal. Large randomized controlled trials with unselected patients, using morbidity and mortality as outcomes, are needed.

Topics: Adult; Aged; Anemia; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium; Canada; Chronic Disease; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Heart Ventricles; Hemoglobins; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases; Lipids; Male; Middle Aged; Organ Size; Parathyroid Hormone; Phosphates; Recombinant Proteins; Renal Dialysis; Single-Blind Method; Treatment Failure; Ultrasonography

At present, oncologists prescribe chemotherapy according to standard dose schedules, and as a result many patients develop serious, dose-limiting toxic effects such as anaemia. We aimed to develop a prediction model for anaemia in patients with breast cancer who were receiving adjuvant chemotherapy.. We reviewed medical records of 331 patients who had received adjuvant chemotherapy for breast cancer. Patients were divided randomly into a derivation sample (n=221) and internal-validation sample (n=110). An external sample of 119 patients enrolled onto the control group of a randomised trial of epoetin alfa was used to validate the model further. Multivariable logistic regression was applied to develop the initial model. We then developed a risk-scoring system, ranging from 0 (low risk) to 50 (high risk), based on the final regression variables. A receiver operating characteristic (ROC) curve analysis was done to measure the accuracy of the scoring system when applied to both validation samples.. The risk of anaemia increased as the pretreatment haemoglobin concentration decreased and was reduced with successive chemotherapy cycles. Risk was also predicted by a platelet count of 200x10(9) cells/L or less before chemotherapy, age 65 years or older, type of adjuvant chemotherapy, and use of prophylactic antibiotics. ROC analysis had acceptable areas under the curve of 0.88 for the internal-validation sample and 0.84 for the external validation sample. A risk score of > or = 24 to < 25 before chemotherapy was identified as the optimum cut-off for maximum sensitivity (83.5%) and specificity (92.3%) of the prediction model.. The application and continued refinement of this prediction model will help oncologists to identify patients at risk of developing anaemia during chemotherapy for breast cancer, and might enhance patient-centred care by the application of anaemia treatment in a proactive and appropriate way.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Epoetin Alfa; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Logistic Models; Medical Records; Middle Aged; Predictive Value of Tests; Recombinant Proteins; Risk Factors; ROC Curve

Changes in blood viscosity and total peripheral resistance may contribute to increased blood pressure during partial correction of renal anemia with erythropoietin. An increase in hemoglobin level is followed by decreases in cardiac output and left ventricular mass. We examined how normalization of hemoglobin in predialysis patients affects both hemorheological and hemodynamic variables.. Twelve moderately anemic predialysis patients (hemoglobin 115.9+/-7.8 g/l) received epoetin-alpha with the aim of achieving a normal hemoglobin level (135-160 g/l). Hemorheological variables were measured using rotational viscometry. Cardiac index was determined by means of Doppler echocardiography.. After 48 weeks, the hematocrit level had increased from 37.9%+/-3.0% to 47.0%+/-3.1% (p<0.0001). Blood viscosity increased from 3.84+/-0.33 to 4.59+/-0.4 mPa x s (p<0.001). Blood viscosity standardized to a hematocrit level of 45% and a plasma viscosity of 1.31 mPa x s did not change. Plasma viscosity, erythrocyte aggregation tendency and erythrocyte fluidity remained unchanged. The cardiac index decreased from 2.64+/-0.57 to 2.19+/-0.72 l/min/m(2) (p<0.05). The total peripheral resistance index increased from 3270+/-985 to 4013+/-1046 (dyn x s/cm(5))m(2) (p<0.05). Blood pressure remained constant, but the amount of antihypertensive medication used increased by 30%.. Hemoglobin normalization in predialysis patients raised blood viscosity and total peripheral resistance due to an increase in hematocrit level, without other consistent hemorheological changes. Antihypertensive therapy had to be increased in many patients to maintain an acceptable blood pressure. The cardiac index was reduced, which may have prevented further development of left ventricular hypertrophy.

Topics: Anemia; Blood Viscosity; Cardiac Output; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Treatment Outcome; Vascular Resistance

This randomized, double-blind, placebo-controlled trial (N93-004) evaluated the effects of epoetin alfa on tumor response to chemotherapy and survival in patients with small-cell lung cancer (SCLC).. Adult patients with hemoglobin < or = 14.5 g/dL starting chemotherapy received epoetin alfa 150 U/kg or placebo subcutaneously 3 times weekly until 3 weeks after completion of chemotherapy. Survival was assessed for 3 years. The primary end point was the proportion of patients with complete or partial response after three chemotherapy cycles.. The trial was terminated prematurely after 224 of a projected 400 patients were accrued. Baseline characteristics were similar between groups. Epoetin alfa and placebo patients (n = 109 and n = 115, respectively) had mean baseline hemoglobin of 12.8 g/dL and 13.0 g/dL, respectively. Overall tumor response was similar between the epoetin alfa and placebo groups after three chemotherapy cycles (72% and 67%, respectively; 95% CI of difference, -6% to 18%) and after completion of chemotherapy (60% and 56%, respectively; 95% CI of difference, -9% to 17%). Epoetin alfa and placebo groups had similar median overall survival (10.5 and 10.4 months, respectively) and overall mortality (91.7% and 87.8%, respectively; hazard ratio, 1.172; 95% CI, 0.887 to 1.549; P = .264). Hemoglobin was maintained in the prechemotherapy range in epoetin alfa patients, but decreased substantially in placebo patients. Fewer epoetin alfa patients than placebo patients required transfusion.. These results suggest that in newly diagnosed patients with SCLC epoetin alfa does not affect tumor response to chemotherapy or survival. However, the early trial closure makes these conclusions preliminary.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Lung Neoplasms; Middle Aged; Placebos; Recombinant Proteins; Survival Analysis

Anaemia is present in 30%-90% of all patients with cancer, and its origin is multifactorial. Human recombinant erythropoietin has been shown to be useful in treating anemia in patients with cancer. The aim of this study was to evaluate the effectiveness of treatment of anaemia with epoetin alfa(EPO) given as a single weekly dose, and its repercussions on quality of life (QoL).. From January to October 2002, a total of 139 patients referred to our service for radiotherapy (RT) had anemia and received treatment with EPO as a single weekly dose of 40,000 IU subcutaneously, with oral iron supplement If haemoglobin (Hb) values after 1 month of treatment did not increase by > or =1 g/dl, the dose was increased to 60,000 IU/week. Treatment with EPO ended when Hb values reached > or =14 g/dl or one month after the end of RT regardless of Hb values. QoL was evaluated with the Functional Assessment of Cancer Therapy-Anaemia subscale (FACT-An) and the Cancer Linear Analogue Scale (CLAS).. Mean Hb at the start of treatment with EPO was 11.49 +/- 1.08 g/dl, and the mean value at the end of treatment was 14.52 +/- 1.41 g/dl (p < 0.001). The mean increase in Hb was 2.97 +/- 1.65 g/dl. Mean duration of treatment was 7.13 +/- 2.91 weeks. In 11 patients (7.9%) the dose was increased after 4 weeks. In 84 patients (60.4%) EPO treatment was implemented before the commencing of RT. Mean Hb values in this group was 11.34 +/- 1.11 g/dl at the start of EPO treatment, 12.69 +/- 1.56 g/dl at the start of RT, 13.96 +1.54 g/dl at the end of RT and 14.68 +/- 1.3 g/dl at the end of EPO treatment (p < 0.001). In 55 patients(39.6%) anaemia developed during RT and, therefore, EPO treatment was implemented after commencing of RT. In this group the mean Hb values were 12.29 +/- 1.6 g/dl at the start of RT, 11.72 +/- 1.01 g/dl at the start of EPO treatment, 13.97 +/- 1.53 g/dl at the end of RT and 14.28 +/- 1.54 g/dl at the end of EPO treatment (p < 0.001). Hemoglobin levels at the start of EPO were lower in patients who commenced EPO before RT (p < 0.05). In 60 patients who received combined RT and chemotherapy, mean Hb values were 11.42 +/- 1.16 g/dl at the start of EPO and 13.98 +1.55 g/dl at the end of EPO (p < 0.005). In 75 patients who had received RT alone, the mean Hb values was 11.53 +/- 1.05 g/dl at the start of EPO and 14.98 +/- 1.17 g/dl at the end of treatment (p < 0.001). Patients treated with RT alone had higher Hb levels at the end of RT and at the end of EPO treatment than did patients who had received combined treatment(p < 0.005). The duration of EPO treatment was shorter in the group treated with RT alone than in the combined treatment group (6.41 +/- 2.99 weeks versus 7.96 +/- 2.67 weeks; p < 0.005). No significant differences were observed in FACT-An and CLAS scores at the beginning and the end of the study.. Treatment with epoetin alfa as a single weekly dose significantly increased Hb levels in patients with cancer who were undergoing radiotherapy. The response was greater in patients treated with radiotherapy alone than in those receiving combined therapy. The duration of EPO treatment was shorter in the group treated with radiotherapy alone than in the combined treatment group.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Transfusion; Combined Modality Therapy; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Treatment Outcome

Current chemotherapy regimens for breast cancer result in high incidences of anemia, which can be treated with erythropoietic agents. The relative efficacy of darbepoetin alfa and epoetin alfa was explored in this phase II, open-label, randomized, multicenter trial in anemic patients with breast cancer receiving chemotherapy.. Patients were randomized at a 1:1 ratio to receive darbepoetin alfa 200 microg every 2 weeks (n = 72) or epoetin alfa 40,000 U weekly (n = 69) for < or = 16 weeks. Clinical and hematologic endpoints and validation of a novel patient satisfaction questionnaire for anemia treatment were evaluated for all patients randomized to receive > or = 1 dose of study drug.. Baseline characteristics were generally similar between treatment groups. Mean changes in hemoglobin (Hb) level from baseline were similar at 1.9 g/dL for darbepoetin alfa and 1.7 g/dL for epoetin alfa. Hematopoietic responses (> or = 2 g/dL increase in Hb level from baseline or Hb level > or = 12 g/dL) were also similar between groups (88% for darbepoetin alfa and 81% for epoetin alfa). The proportions of patients who received a transfusion during treatment were 6% (95% CI, 0-11%) for darbepoetin alfa and 16% (95% CI, 7%-25%) for epoetin alfa. Most patients (67 patients receiving darbepoetin alfa [93%]; 61 patients receiving epoetin alfa [90%]) exhibited a clinically meaningful target Hb level > or = 11 g/dL. No differences in safety were observed.. These results suggest that, in patients with breast cancer, darbepoetin alfa 200 microg every 2 weeks and epoetin alfa 40,000 U weekly result in comparable clinical outcomes for the treatment of chemotherapy-induced anemia.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Humans; Middle Aged; Patient Satisfaction; Recombinant Proteins; Treatment Outcome

This study in patients with cancer and anemia, who were receiving chemoradiation and were treated with epoetin alfa, examined the relationship between hemoglobin level and quality of life (QOL), change in hemoglobin and change in QOL, and incremental (1 g/dL) increase in hemoglobin and related incremental improvement in QOL. Data from a multicenter, open-label, prospective study of once-weekly epoetin alfa therapy in anemic cancer patients receiving chemoradiation were used to retrospectively evaluate the relationship between hemoglobin changes and QOL changes via correlation and longitudinal analyses. A sample selection correction method was used to ensure unbiased results. QOL (energy, activity, overall QOL) was measured using the Linear Analog Scale Assessment. An incremental analysis determined the greatest incremental increase in QOL associated with a 1 g/dL increase in hemoglobin level. Of the 777 patients enrolled, 464 met chemotherapy and radiotherapy eligibility criteria. Of these, 359 (77%) underwent two QOL assessments and were eligible for analysis. A nonlinear and statistically significant positive correlation was found between hemoglobin levels and Linear Analog Scale Assessment QOL scores (r = 0.32 [energy], 0.33 [activity], and 0.29 [overall QOL]; P < .0001). An incremental analysis used regression methods to characterize the changes in hemoglobin levels and QOL scores. Hemoglobin change was found to be a statistically significant determinant of QOL changes (P < .05). The greatest incremental QOL gain associated with a 1-g/dL change in hemoglobin occurred around hemoglobin 12 g/dL (range, 11-13 g/dL). A direct relationship exists between hemoglobin increases and corresponding QOL increases. Maximal incremental gain in QOL occurred when hemoglobin was approximately 12 g/dL (range, 11-13 g/dL).

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Patient Selection; Polypharmacy; Quality of Life; Recombinant Proteins

It is not known whether prevention of anemia among patients with chronic kidney disease would affect the development or progression of left ventricular (LV) hypertrophy. A randomized controlled trial was performed with 155 patients with chronic kidney disease (creatinine clearance, 15 to 50 ml/min), with entry hemoglobin concentrations ([Hb]) of 110 to 120 g/L (female patients) or 110 to 130 g/L (male patients). Patients were monitored for 2 yr or until they required dialysis; the patients were randomized to receive epoetin alpha as necessary to maintain [Hb] between 120 and 130 g/L (group A) or between 90 and 100 g/L (group B). [Hb] increased for group A (from 112 +/- 9 to 121 +/- 14 g/L, mean +/- SD) and decreased for group B (from 112 +/- 8 to 108 +/- 13 g/L) (P < 0.001, group A versus group B). On an intent-to-treat analysis, the changes in LV mass index for the groups during the 2-yr period were not significantly different (2.5 +/- 20 g/m(2) for group A versus 4.5 +/- 20 g/m(2) for group B, P = NS). There was no significant difference between the groups in 2-yr mean unadjusted systolic BP (141 +/- 14 versus 138 +/- 13 mmHg) or diastolic BP (80 +/- 6 versus 79 +/- 7 mmHg). The decline in renal function in 2 yr, as assessed with nuclear estimations of GFR, also did not differ significantly between the groups (8 +/- 9 versus 6 +/- 8 ml/min per 1.73 m(2)). In conclusion, maintenance of [Hb] above 120 g/L, compared with 90 to 100 g/L, had similar effects on the LV mass index and did not clearly affect the development or progression of LV hypertrophy. The maintenance of [Hb] above 100 g/L for many patients in group B might have been attributable to the relative preservation of renal function.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Time Factors

Anaemia correction in patients with end-stage renal disease has been enhanced following the use of epoetin alfa or beta and there are a number of studies detailing its application. Dialysis centres are dealing with greater numbers of elderly patients and anaemia correction in these individuals may differ by virtue of co-existing comorbidity and their age.. The aim of this study was to examine the response of the elderly patients to anaemia correction using a locally devised anaemia correction protocol while receiving dialysis.. An incident, non-randomised, cohort observational study in a single centre was used to compare the correction of anaemia in a population of elderly (> or =65 years of age) and young dialysis patients. All incident patients starting peritoneal dialysis and haemodialysis (HD) between January 1998 and December 2000 were selected and treated using a locally devised anaemia correction protocol and observed for at least 1 year. Anaemia correction following adjustments for factors such as age, comorbidity, dialysis type, dialysis access type and predialysis nephrological care was assessed.. 198 patients commenced dialysis with 86 elderly patients (mean age +/- SD 73.7 +/- 4.9 years). The elderly patients had similar periods of predialysis nephrological care as the younger patients. Most patients received HD and required a tunnelled dialysis catheter (TC) as vascular access. Equivalent numbers of elderly patients received peritoneal dialysis. Comorbid scores were greater in the elderly and patient survival was dependent upon these comorbid factors. Following the strict use of TCs, patient survival was similar to those patients commencing HD with arterio-venous fistulae. Anaemia correction in the elderly was similar to the younger patients, with a median haemoglobin of 11.3 g/dL. By 6 months of dialysis, most patients achieved the UK Renal Association anaemia correction standard (haemoglobin above 10 g/dL). The elderly patients maintained significantly higher serum ferritin levels throughout (median 209 microg/L) and required less epoetin alfa or beta (median 91.6 units/kg/wk), indicating that functional iron deficiency in the elderly dialysis patients is less. Intravenous iron sucrose doses were similar in both age groups and iron overload (serum ferritin above 800 microg/L) had been avoided following the use of the intravenous iron protocol.. The study has noted that elderly patients responded to anaemia corrective therapies as well as the younger patients, despite greater levels of comorbidity while requiring less epoetin alfa or beta.

Topics: Aged; Aged, 80 and over; Aging; Anemia; Comorbidity; Epoetin Alfa; Erythropoietin; Ferritins; Geriatrics; Humans; Kidney Failure, Chronic; Middle Aged; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis; Survival Analysis; Treatment Outcome

Darbepoetin alfa is an erythropoiesis-stimulating glycoprotein with up to 3 times longer half-life than recombinant human erythropoietin (rHuEPO) in humans. The aim of this study was to assess the efficacy and safety of darbepoetin alfa given once every other week as treatment of anemia in predialysis patients with chronic renal failure (CRF) previously treated with once-weekly epoetin alfa. A total of 42 CRF patients were included, all of whom had previously been treated with epoetin alfa and showed stable hemoglobin (Hb) levels without dose changes during the last 8 weeks prior to enrolment in this study. All patients received s.c. darbepoetin alfa once every other week at doses calculated from the protein mass equivalence between rHuEPO and darbepoetin alfa. Follow-up lasted for 24 weeks. Dose adjustments were conducted to preserve target Hb levels between 11 and 13 g/dl. Thirty-nine patients completed the 24 weeks of study. Hb levels increased during follow-up [mean values of 0.39 (p < 0.002), 0.58) (p < 0.001), and 0.83 g/dl (p < 0.001) at 8, 16 and 24 weeks, respectively] despite reducing the darbepoetin alfa dose up to 15% at 24 weeks [from 0.192 microg/kg body weight to 0.185, 0.178 and 0.163 at 8, 16, and 24 weeks, respectively (p < 0.001)]. No adverse events related to darbepoetin alfa were reported. In conclusion, these results show s.c. administration of darbepoetin alfa once every other week was superior to weekly epoetin alfa as a maintenance treatment for anemia in predialysis CRF patients, since the former provided higher Hb levels. Moreover, darbepoetin alfa administration was safe in these patients.

Topics: Aged; Anemia; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Humans; Kidney Failure, Chronic; Male; Prospective Studies; Recombinant Proteins

Anaemia is a key component of diabetic nephropathy, but its importance has only recently been recognised. Recombinant human erythropoietin (epoetin) is an established treatment for renal anaemia, and may help to reduce complications associated with diabetic nephropathy, such as cardiovascular disease. The limited experience with the use of epoetin in this patient group prompts the urgent need for clinical data on anaemia correction in early diabetic nephropathy, particularly with regard to benefits on cardiovascular risk reduction. The Anaemia CORrection in Diabetes (ACORD) study will investigate the effects of anaemia correction on cardiac structure and function in patients with early diabetic nephropathy. This 15-month multicentre study will recruit 160 adult patients with diabetes, mild or moderate chronic kidney disease (with creatinine clearance >or=30 ml/min at screening) and moderate anaemia (haemoglobin [Hb], 10.5-13.0 g/dl). Patients will be randomised to one of two groups: the early treatment group will receive subcutaneous epoetin beta (NeoRecormon) at study entry to maintain target Hb levels of 13-15 g/dl, while the control group will reflect current practice and will not receive epoetin therapy until Hb levels decline below 10.5 g/dl. The primary efficacy variable, change in left ventricular mass index, will be evaluated at 15 months following randomisation; secondary efficacy variables will include changes in cardiac structure and function over the study period. The ACORD study should provide valuable information on the benefits of anaemia correction in patients with early diabetic nephropathy. The study will also increase awareness of the importance of treating anaemia associated with diabetes.

Topics: Anemia; Clinical Trials as Topic; Diabetic Nephropathies; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Analysis; Time Factors

Combination therapy with interferon alpha (IFN-alpha) and ribavirin (RBV) or pegylated IFN-alpha (PEG-IFN-alpha)/RBV for chronic hepatitis C virus (HCV) infection often causes anemia, prompting RBV dose reduction/discontinuation. This study assessed whether epoetin alfa could maintain RBV dose, improve quality of life (QOL), and increase hemoglobin (Hb) in anemic HCV-infected patients.. HCV-infected patients (n = 185) on combination therapy who developed anemia (Hb < or = 12 g/dL) were randomized into a U. S. multicenter, placebo-controlled, clinical trial of epoetin alfa, 40,000 U subcutaneously, once weekly vs. matching placebo. The study design used an 8-week, double-blind phase (DBP) followed by an 8-week, open-label phase (OLP), in which placebo patients were crossed over to epoetin alfa.. At the end of the DBP, RBV doses were maintained in 88% of patients receiving epoetin alfa vs. 60% of patients receiving placebo (P < 0.001). Mean QOL scores at the end of the DBP improved significantly on all domains of the Linear Analog Scale Assessment (LASA) and on 7 of the 8 domains of the Short Form-36, version 2 (SF-36v2). Mean Hb increased by 2.2 +/- 1.3 g/dL (epoetin alfa) and by 0.1 +/- 1.0 g/dL (placebo) in the DBP (P < 0.001). Similar results were demonstrated in patients who switched from placebo to epoetin alfa in the OLP. Epoetin alfa was well tolerated; the most common adverse effects were headache and nausea.. Epoetin alfa maintained RBV dose and improved QOL and Hb in anemic HCV-infected patients receiving combination therapy.

Topics: Adult; Aged; Anemia; Antiviral Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Hepatitis C; Humans; Interferon-alpha; Liver; Liver Function Tests; Male; Middle Aged; Quality of Life; Recombinant Proteins; Ribavirin; Viral Load

Numerous prior studies have reported that a substantially higher dose of epoetin is required to maintain haemoglobin (Hb) concentration when patients are switched from a subcutaneous (s.c.) to intravenous (i.v.) route of administration. Many of the reported trials, however, involved patients who did not have adequate serum iron levels. It was hypothesized that patients with adequate iron stores who are switched from one route of administration to the other without a change in dose will experience substantially less change in their Hb concentration.. Haemodialysis patients who were iron replete (ferritin 300-800 microg/L, transferrin saturation (TSAT) 25-50%) participated in a prospective, randomized cross-over trial receiving epoetin for 3 months either by s.c. or i.v. injection followed by a further 3 months of epoetin via the other route. The principal aim was to determine changes in Hb concentration without altering the weekly epoetin dose. The secondary aim was to assess whether the frequency of dosing (once, twice or thrice weekly) influenced the Hb concentration response.. Eighty-one patients (mean age 62 years, 60% male) entered the study and 15 withdrew prior to study completion. Forty-three patients began s.c. epoetin alfa administration (group A) and 38 on i.v. (group B). Median ferritin and TSAT at entry for groups A and B were 409 and 394 microg/L (NS) and 31 and 32% (NS), respectively, which remained within the target range during the study. Median epoetin doses for groups A and B were similar (90 vs 93 IU/kg per week, NS). After 3 months, the mean Hb concentration rose for group A (SC; 118.7-121.9 g/L (P = 0.03)) but it fell for group B (i.v.; 119.1-116.0 g/L (P = 0.019)). Following the change in route of administration, the Hb concentration for group A (i.v.) fell by 5.1% over 3 months (121.9-115.4, P < 0.001) and rose by 2.8% for group B (s.c.) over 3 months (116.0-119.7, P = 0.001). Similar significant changes in the Hb concentration were seen at different dosing frequencies.. Subcutaneous administration of epoetin produces a significant, although slight clinical change in Hb concentration compared with i.v. administration in stable, iron replete, haemodialysis patients. A similar effect appears to prevail regardless of the frequency of injections given.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Cross-Over Studies; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Iron; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

Anemia occurs in approximately 47% of patients with chronic kidney disease (CKD) not on dialysis. Recombinant human erythropoietin (r-HuEPO, epoetin alfa) has been proven safe and effective for anemia treatment in patients with CKD using a three times-weekly regimen. The current study was conducted to evaluate the clinical safety and efficacy of a less frequent dosing regimen (once weekly) in this population.. This prospective, multicenter, open-label, non-randomized study enrolled 1,557 adult anemic (hemoglobin (Hb) < or = 10 g/dl) CKD patients not on dialysis. Epoetin alfa 10,000 U was administered subcutaneously once weekly for 16 weeks. Titration to 20,000 U once weekly at week 5 was permitted if patients had an increase in Hb < 1 g/dl. Safety and efficacy were assessed by changes in health-related quality of life (Linear Analog Scale Assessment (LASA) and Kidney Disease Questionnaire (KDQ)), changes in hematologic parameters and transfusion utilization, and incidence and severity of adverse events.. 1,338 patients were evaluable for efficacy. Mean Hb level increased from 9.1 g/dl at baseline to 11.6 g/dl at study completion (last observed value after baseline) (p < 0.0001). Overall, 89.8% of patients responded to once-weekly dosing, exhibiting an increase in Hb level of > or = 1 g/dl from baseline. The percentage of patients that required transfusion decreased from 11.1% (baseline) to 3.7% (during the study) (p < 0.0001). All quality-of-life parameters improved significantly from baseline (p < 0.0001). Mean LASA scores for energy, activity and overall quality of life increased from baseline to study completion by 27.9 mm (70.5%), 24.5 mm (57.0%) and 22.6 mm (47.4%), respectively. All 5 KDQ domains showed statistically significant improvements (p < 0.0001). Hb change was a strong predictor for all 5 KDQ domains and the overall score (p < 0.0001). Treatment with once-weekly epoetin alfa was well tolerated, similar to that reported with three times-weekly dosing.. Once-weekly epoetin alfa therapy is safe and effective for treating anemia in patients with CKD not on dialysis, and is associated with significant improvements in functional status and quality of life.

Topics: Aged; Analysis of Variance; Anemia; Blood Transfusion; Chronic Disease; Comorbidity; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Prospective Studies; Quality of Life; Recombinant Proteins; Regression Analysis; Treatment Outcome

Catheter-related infection (CRI) is a major cause of morbidity and mortality in patients receiving hemodialysis. Antibiotic locking of these catheters has been shown to increase both the success of systemic antibiotic treatment in line sepsis, and to reduce the incidence of sepsis. We have studied the use of gentamicin locking of catheters (in combination with standard heparin rather than previously reported citrate) to reduce CRI rates. Furthermore, we have investigated the effects of this strategy on epoetin requirements and vascular access function.. Fifty patients were studied. Patients were randomized to catheter-restricted filling with either standard heparin (5000 IU/mL) alone, or gentamicin and heparin (5 mg/mL). Epoetin requirements and hemoglobin response were monitored over the study period.. The gentamicin-locked group suffered only one infective episode (0.3/1000 catheter days) compared to 10 episodes in six patients in the heparin alone group (4/1000 catheter days, P= 0.02). The isolated organisms were equally split between Staphylococcal species and coliforms. There were no statistically significant differences in delivered dialysis dose (Kt/V) or QA between the two groups. Use of antibiotic locking was associated with both a higher mean hemoglobin (10.1 +/-0.14 g/dL vs. 9.2 +/- 0.17 g/dL in the heparin group, P= 0.003) and a lower mean epoetin dose (9000 +/- 734 IU/week vs. 10790 +/-615 IU/week in the heparin group, P= 0.04).. The practice of locking newly inserted tunneled central venous catheters with gentamicin and heparin is an effective strategy to reduce line sepsis rates, and is associated with beneficial effects on epoetin requirements.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Anti-Bacterial Agents; Anticoagulants; Catheterization; Cross Infection; Epoetin Alfa; Erythropoietin; Female; Gentamicins; Hematinics; Heparin; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Sepsis

Epoetin alfa, administered at standard dosages of 10,000-20,000 IU three times weekly or 40,000-60,000 IU once weekly, has been shown to significantly increase hemoglobin (Hb) levels, decrease transfusion requirements, and improve quality-of-life parameters in patients undergoing chemotherapy.Objective. This open-label, nonrandomized, historically controlled study was conducted to evaluate the efficacy and safety of an induction dose of epoetin alfa in patients with moderate or severe anemia who were receiving chemotherapy.. Nineteen patients with solid tumors and Hb levels < 9.0 g/dl were enrolled. The patients received single s.c. injections of epoetin alfa, 40,000 IU, on study days 1, 4, 7, 10, and 13, and were then observed for the following 30 days. Nineteen other cancer patients who had matching characteristics and had received epoetin alfa, 10,000 IU, three times weekly for the 45-day study period, served as historical controls. The primary efficacy variable was change in Hb level from baseline to days 15 (approximately week 2) and 45 (approximately week 6.5). Secondary efficacy variables included the percent response (Hb increase > or = 1 g/dl) and percent major response (Hb increase > or = 2 g/dl) at days 15 and 45, the durations of response and major response after day 45, the proportion of patients transfused within the 45 study days, the changes in Eastern Cooperative Oncology Group performance status score at days 15 and 45, and the ability to maintain the planned chemotherapy dose (dose intensity) over the 45-day study.. Mean increases in Hb level in the epoetin alfa 40,000 IU group were significantly greater than those in the historical control group both at day 15 and at day 45. The increase in Hb level in the control group approximated increases reported with standard 3-times-weekly epoetin alfa at day 15 but was somewhat lower than the increases typically seen by day 45, presumably due to the fact that, in the present study, the epoetin alfa dose was not doubled in initial nonresponders, as is commonly done with standard epoetin alfa treatment. The rates of major response for epoetin alfa 40,000 IU patients (37% at day 15 and 84% at day 45) were higher than those for control patients (16% and 21%, respectively). Also, the transfusion rate was lower and performance status scores were better in the epoetin alfa 40,000 IU patients than in the control patients. In all, 74% of epoetin alfa 40,000 IU patients versus 47% of control patients received 100% of the planned chemotherapy dose. Epoetin alfa was well tolerated in both treatment groups.. Results of this study suggest that epoetin alfa at a dose of 40,000 IU administered five times over 2 weeks may confer even higher response rates than those seen with standard dosing regimens. These encouraging results support further study of the proposed induction dose of epoetin alfa in a larger, randomized, prospectively controlled trial.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Case-Control Studies; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Remission Induction; Treatment Outcome

Non-small cell lung cancer (NSCLC) treatment with new drugs in combination with platinum salts induce anemia G1/2 and G3/4 WHO in about 35 and 10-20% of patients, respectively, with a chemotherapy (CT) dose intensity decrease in 20% of cases. Epoetin alfa, administered at standard dosages has been shown to significantly increase hemoglobin (Hb) levels, decrease transfusion requirements, and improve quality-of-life parameters in patients undergoing chemotherapy.. This open-label, non-randomized study was conducted to evaluate the efficacy and safety of an induction dose of epoetin alfa 40.000 IU in lung cancer patients with moderate or severe anemia who were receiving CT.. Twenty-four patients (8 SCLC and 16 NSCLC) were enrolled in the study to receive single subcutaneous (s.c.) injections of epoetin alfa 40.000 IU on days 1, 4, 7, 10, and 13, followed by standard treatment (10.000 IU t.i.w.) for the further 2 weeks. Nine patients had been previously treated with epoetin alfa 10.000 IU t.i.w. Twenty-two patients were receiving first-line CT and two patients were receiving docetaxel as second-line CT.. After 15 days of treatment, in 21 evaluable patients, Hb was 10.5 +/- 1.3 g/dL (mean +/- S.D.), with a mean increase from baseline of 2.0 g/dL (95%CI: 1.3-2.7). Hb increase was > or =2g/dL in 11 patients, 1-1.9 g/dL in 5 patients, and <1g/dL in 5 patients. After 30 days of treatment, Hb was 11.5 +/- 0.8 g/dL (mean +/- S.D.), with a mean increase from baseline of 2.9 g/dL (95%CI: 2.4-3.4) in 20 evaluable patients. No adverse events possibly related to epoetin alfa treatment were observed.. An induction therapy with epoetin alfa 40.000 IU for 2 weeks followed by standard treatment allows an Hb increase of 2.9 g/dL even in advanced lung cancer patients with a moderate/severe anemia, without RBC transfusion requirements. A randomized study of the proposed induction dose of epoetin alfa 40.000 IU is actually ongoing.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Lung Neoplasms; Male; Middle Aged; Recombinant Proteins; Treatment Outcome

An important clinical question is the relative efficacy of the most common dosages of darbepoetin alfa (Aranesp; Amgen Inc.; Thousand Oaks, CA) 200 microg every 2 weeks (Q2W) and epoetin alfa (Procrit; Ortho Biotech Products, LP; Raritan, NJ) 40,000 U weekly (QW) for the treatment of chemotherapy-induced anemia. We designed three concurrent randomized, open-label, multicenter, identical trials (with the exception of tumor type criteria of breast, gynecologic, or lung cancer) of darbepoetin alfa and epoetin alfa in patients with chemotherapy-induced anemia to validate the Patient Satisfaction Questionnaire for Anemia (PSQ-An) treatment tool and to compare the efficacies and safety profiles of these two agents. In each trial, patients were randomized 1:1 to receive either darbepoetin alfa at a dose of 200 microg Q2W or epoetin alfa at a dose of 40,000 U QW for up to 16 weeks. The PSQ-An was assessed for validity, feasibility, and reliability. Secondary clinical endpoints were analyzed using the primary analysis set. Both individual trial analyses and a protocol-specified combined analysis of data from all three trials were conducted. Overall, 312 patients (157 darbepoetin alfa; 155 epoetin alfa) were randomized and received study drug. Baseline characteristics were similar in both treatment groups in each trial and overall. The PSQ-An was valid, feasible, and reliable. In general, no difference between treatment groups was observed for hemoglobin- and transfusion-based endpoints in each individual trial or in the combined analysis. From exploratory analyses, achievement and maintenance of a hemoglobin target range (11-13 g/dl) were similar in both groups. No differences in safety were observed. With the PSQ-An, formal comparisons of the impact of anemia therapies on patients and caregivers can be made in future prospective studies. Further, darbepoetin alfa (200 microg Q2W) and epoetin alfa (40,000 U QW) appear to achieve comparable clinical and hematologic outcomes.

Topics: Anemia; Antineoplastic Agents; Breast Neoplasms; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Genital Neoplasms, Female; Hematinics; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Quality of Life; Recombinant Proteins; Reproducibility of Results; Surveys and Questionnaires

Anemia and decreased health-related quality of life (HRQL) are common in patients receiving combination therapy of interferon alfa (IFN) and ribavirin (RBV) for chronic hepatitis C virus (HCV) infection. In a randomized, prospective study evaluating the effectiveness of epoetin alfa in maintaining RBV dose, alleviating anemia, and improving HRQL in anemic (Hb < or = 12 g/dL) HCV-infected patients receiving combination therapy, patients receiving epoetin alfa had significant improvements in HRQL compared with placebo. In this study, 185 patients were randomized to 40,000 units of epoetin alfa subcutaneously weekly or placebo for an 8-week double-blind phase (DBP), followed by an 8-week open-label phase during which all patients received epoetin alfa. To further assess the impact of epoetin alfa on HRQL, post hoc analyses were conducted in the same patient population to compare the HRQL of these patients at randomization with norms of other populations, and to determine the critical relationship between hemoglobin (Hb) levels and HRQL. Mean HRQL scores of anemic HCV-infected patients receiving combination therapy at randomization were significantly lower than those of both the general population and patients who had other chronic conditions. Patients receiving epoetin alfa who had the greatest Hb increases from randomization to the end of the DBP also had the largest improvements in HRQL. Hb improvement was an independent predictor of HRQL improvement in these patients. In conclusion, epoetin alfa provided clinically significant HRQL improvement in HCV-infected patients receiving IFN/RBV therapy.

Topics: Adult; Aged; Anemia; Antiviral Agents; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Hepatitis C, Chronic; Humans; Interferon-alpha; Liver Cirrhosis; Male; Middle Aged; Quality of Life; Recombinant Proteins; Ribavirin

This prospective, open-label, multicenter trial evaluated the effects of once-weekly (qw) epoetin alfa on quality of life (QOL) and hemoglobin (Hb) levels in anemic human immunodeficiency virus (HIV)-infected adult receiving antiretroviral therapy. A total of 650 patients with Hb < or = 11 g/dl received epoetin alfa 40,000 U qw subcutaneously, with dose escalation to 60,000 qw if Hb increase was <1 g/dl after 4 weeks. The linear Analog Scale Assessment (LASA) overall QOL score, LASA energy score, and LASA activity score each significantly improved from baseline to final measurement (p < 0.0001 for each parameter). Improvements in the Medical Outcomes Study (MOS)-HIV physical and mental health summary scores were also significant (p < 0.0001), and coincided with Hb increases. Mean Hb increased from baseline to final measurement by 2.5 g/dl (95% CI: 2.3, 2.6 g/dl; p < 0.0001). Objective hematological response rate, defined as a > or = 1 g/dl Hb increase from baseline to week 8, was 86%. Hemoglobin increased significantly in all subgroups of race, zidovudine use, CD4+ cell count, and viral load. Once-weekly epoetin alfa was well tolerated. Once-weekly epoetin alfa is effective in improving QOL and Hb measures.

Topics: Adult; Aged; Anemia; Antiretroviral Therapy, Highly Active; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; HIV Infections; Humans; Male; Middle Aged; Quality of Life; Recombinant Proteins; Treatment Outcome

The communication is summarizing results of study aimed to ascertain the efficacy of treatment with epoetin alpha in patients with different hematological disorders and, at the same time to evaluate the impact of this treatment on quality of their lives. Treatment efficacy in separate patients of the monitored population has been evaluated not only according to hemoglobin level increase, but also according to its effect on erythrocyte products consumption needed to control anemic syndrome. Overall 134 patients with different lymphoproliferative disorders were included in the evaluation. Full-extended monitoring, i.e. at least 3-month treatment with epoetin alpha, was passed by 127 (94.8%) patients. Favorable effect of epoetin alpha administration was most often reported in patients with multiple myeloma (85.7%), Waldenstrom s macroglobulinemia (80%) and chronic lymphatic leukemia (76.7%). Conversely the lowest efficacy was reported in the group of patients with myelodysplastic syndrome. Administration of epoetin alpha within treatment of underlying anemia in numerous hematological disorders represents suitable alternative to the substitution therapy via erythrocyte transfusions. Approximately 75% of monitored patients showed improvement of life quality, in some cases irrespective of results of treatment of their underlying disorder.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematologic Neoplasms; Humans; Male; Quality of Life; Recombinant Proteins; Treatment Outcome

Anemia, highly common among cancer patients, is often an underlying cause of cancer-related fatigue and other quality-of-life (QOL) deficits. Although randomized clinical trials have shown that treatment with epoetin alfa increases hemoglobin levels, reduces fatigue, lessens transfusion requirements, and improves overall QOL, cancer-related anemia and fatigue remain undertreated. This is, in part, because scales and measures of QOL are still relatively unfamiliar to most clinicians and because population-based reference ranges are lacking, thus making clinical trial results difficult to interpret.. To aid in the interpretation of QOL results from clinical trials, we administered the Functional Assessment of Cancer Therapy-Anemia (FACT-An) QOL instrument to a nationally representative sample of 1,400 people using an Internet survey panel in the United States. We then compared the FACT-An data from the Internet survey with the QOL data of a 375-patient randomized, double-blind clinical trial evaluating epoetin alfa versus placebo in anemic cancer patients.. FACT-An, as administered to the survey population, displayed good psychometric properties and was able to discriminate between respondents with histories of specified illnesses, including anemia and cancer, and those without. Comparison of the population norm and clinical trial data showed that treatment with epoetin alfa resulted in clinically meaningful as well as statistically significant improvements in QOL (P <.01).. Reliable population norm data are now available to aid in the interpretation of clinical trial results where the FACT-An questionnaire is administered. In the clinical trial, treatment with epoetin alfa overcame much of the QOL deficit seen in anemic cancer patients compared with the norm population sample.

Topics: Adolescent; Anemia; Blood Transfusion; Double-Blind Method; Epoetin Alfa; Erythropoietin; Fatigue; Health Status Indicators; Hematinics; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Surveys and Questionnaires; Treatment Outcome

Partial correction of renal anaemia with erythropoietin improves quality of life (QoL). We aimed to examine if normalization of haemoglobin with epoetin alfa in pre-dialysis and dialysis patients further improves QoL and is safe.. 416 Scandinavian patients with renal anaemia [pre-dialysis, haemodialysis (HD) and peritoneal dialysis patients] were randomized to reach a normal haemoglobin of 135-160 g/l (n=216) or a subnormal haemoglobin of 90-120 g/l (n=200) with or without epoetin alfa. Study duration was 48-76 weeks. QoL was measured using Kidney Disease Questionnaires in 253 Swedish dialysis patients. Safety was examined in all patients.. QoL improved, measured as a decrease in physical symptoms (P=0.02), fatigue (P=0.05), depression (P=0.01) and frustration (P=0.05) in the Swedish dialysis patients when haemoglobin was normalized. In pre-dialysis patients, diastolic blood pressure was higher in the normal compared with the subnormal haemoglobin group after 48 weeks. However, the progression rate of chronic renal failure was comparable. In the normal haemoglobin group (N-Hb), 51% had at least one serious adverse event compared with 49% in the subnormal haemoglobin group (S-Hb) (P=0.32). The incidence of thrombovascular events and vascular access thrombosis in HD patients did not differ. The mortality rate was 13.4% in the N-Hb group and 13.5% in the S-Hb group (P=0.98). Mortality decreased with increasing mean haemoglobin in both groups.. Normalization of haemoglobin improved QoL in the subgroup of dialysis patients, appears to be safe and can be considered in many patients with end-stage renal disease.

Topics: Aged; Anemia; Antihypertensive Agents; Blood Pressure; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Hospitalization; Humans; Kidney; Male; Middle Aged; Peritoneal Dialysis; Quality of Life; Recombinant Proteins; Renal Dialysis; Safety; Sick Leave; Thromboembolism

Health-related quality of life (HrQOL) assessments are gaining importance as outcome measures in cancer clinical trials. A recently published clinical trial reported statistically significant (P<0.001) increases in haemoglobin (Hb) levels and significantly (P<0.01) increased HrQOL scores following the administration of recombinant human erythropoietin (r-HuEPO, epoetin alfa) versus placebo to anaemic cancer patients who received non-platinum chemotherapy. This study employed five cancer-specific HrQOL instruments. Hb and HrQOL data from this trial were analysed to estimate the minimally important difference (MID) in HrQOL measures that could be interpreted as clinically meaningful, with Hb level selected as the best external standard. Patients were assigned to two groups: improved (Hb increases of >/=1 g/dL) or stable (change in Hb of-1 g/dL to <1 g/dL). The MID was first determined as the difference between the mean changes in HrQOL in the improved group versus the stable group. By this analysis, the differences in HrQOL scores between the epoetin alfa group and the placebo group were clinically important for all Hb-sensitive, cancer-specific HrQOL evaluations. Linear regression analyses performed to provide estimates of the MID for specific values of Hb change confirmed that the differences in HrQOL scores between patient groups were clinically significant. These analyses were repeated using a data set from a separate clinical trial, which further supported the conclusion that observed HrQOL changes demonstrated in the multicentre, double-blind study were clinically important. These methods provide one means for interpreting the clinical relevance of changes in HrQOL evaluated in clinical trials.

Topics: Anemia; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Regression Analysis

The current study was performed to prospectively evaluate the effectiveness, clinical outcomes, and safety of once-weekly (QW) recombinant human erythropoietin (r-HuEPO [epoetin-alpha]) in anemic cancer patients with nonmyeloid malignancies who were receiving radiation therapy (RT) concomitantly or sequentially with chemotherapy (CT).. A total of 777 anemic patients (hemoglobin [Hb] < or = 11 g/dL) were enrolled in this multicenter, open-label, nonrandomized, 16-week study. Patients initially received epoetin-alpha at a dose of 40,000 units (U) subcutaneously QW, escalating to a dose of 60,000 U QW if the Hb increased to < or = 1 g/dL after 4 weeks. Endpoints were changes in hematologic and quality of life (QOL) parameters.. Among the 442 patients evaluable for hematologic response, the mean increase in Hb from baseline to the time of final evaluation was 1.9 +/- 1.8 g/dL (P < 0.05). An increase in Hb of > or = 2 g/dL, in the absence of blood transfusions, occurred in 68.3% of patients (278 of 407 patients) who were on the study for > or = 30 days. The overall response rate (Hb increase > or = 2 g/dL or Hb > or = 12 g/dL in the absence of blood transfusions) was 74.0% (301 of 407 patients). In 359 patients who were evaluable for QOL assessment, epoetin-alpha therapy was found to significantly (P < 0.05) improve mean Linear Analog Scale Assessment (LASA) scores for energy level, ability to perform daily activities, and overall QOL from baseline to the time of final evaluation. QW epoetin-alpha therapy was found to be well tolerated.. Treatment with QW epoetin-alpha was found to increase Hb levels, decrease transfusion requirements, and improve functional status and QOL in anemic patients with nonmyeloid malignancies who were receiving RT concomitantly or sequentially with CT. Clinical benefits and the safety profile of QW epoetin-alpha in this setting appear to be similar to those observed in anemic cancer patients receiving CT.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Quality of Life; Radiotherapy; Recombinant Proteins

Membrane biocompatibility has long been thought to be relevant to hemodialysis outcomes and, possibly, renal anemia.. We performed a randomized, controlled, single-center study comparing the consequences on renal anemia of 2 dialyzers of equivalent performance, but different composition, during 7 months. Two hundred eleven patients of an unselected dialysis population of 235 patients gave informed consent to undergo random assignment to either group A (SF170E; modified cellulose triacetate/midflux membrane; Nipro, Osaka, Japan) or group B (HF80LS; polysulfone/high-flux membrane; Fresenius, Bad Homburg, Germany). Anemia management was identical in both treatment groups and followed strict clinical protocols managed by computer algorithms. Dialysis adequacy, hemoglobin (Hb) level, ferritin level, percentage of red blood cell hypochromicity, C-reactive protein (CRP) level, and intravenous iron and epoetin doses were monitored monthly.. One hundred seventy-seven patients completed the 7-month study. Equilibrated Kt/V increased in both groups. Hb outcome improved overall, but did not differ between the 2 study groups. Epoetin dose was not significantly different after 7 months compared with baseline in either group. Hb level, epoetin dose, iron status, CRP level, dialysis Kt/V, and residual renal function did not differ between the 2 groups. A slight but significant negative correlation was identified between dialysis Kt/V and Hb level in the population as a whole (Spearman's correlation, -0.16; P = 0.04).. No significant epoetin-sparing effect was identified through the use of the high-flux polysulfone HF80LS membrane over the modified cellulose triacetate SF170E membrane. Although not a primary outcome for this study, there was a suggestion of benefit of improved Hb level, without increased need for epoetin, through increasing delivered dialysis dose.

Topics: Adult; Aged; Anemia; C-Reactive Protein; Cellulose; Epoetin Alfa; Erythrocytes; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Membranes, Artificial; Middle Aged; Parathyroid Hormone; Phosphorus; Polymers; Potassium; Recombinant Proteins; Renal Dialysis; Sulfones

Anemia has been reported in approximately 40%-70% of patients with hematologic malignancies, with severity depending on the type and stage of disease and whether the patient has received myelosuppressive chemotherapy. Growing evidence supports the role of epoetin alfa in correcting anemia and improving quality of life (QOL) in patients with hematologic malignancies. Clinical practice guidelines recommend the use of epoetin alfa in patients with cancer-related anemia (including patients with hematologic malignancies) and hemoglobin levels < or =10 g/dL. Epoetin alfa treatment is optional for patients with cancer-related anemia and hemoglobin levels>10 g/dL and <12 g/dL, depending on clinical circumstances. A prospective, open-label, randomized trial evaluating hematologic response, transfusion use, and QOL after immediate or delayed epoetin alfa treatment in mildly anemic patients (hemoglobin< or =12 g/dL) undergoing chemotherapy for chronic lymphocytic leukemia, multiple myeloma, or lymphoma was recently completed. Study objectives included determining any correlation between changes in hemoglobin level and QOL and assessing any correlation between QOL measures and health care resource use. Interim results suggest that epoetin alfa treatment in patients with hematologic cancers and hemoglobin< or =12 g/dL who are receiving chemotherapy increases hemoglobin, functional capacity, well-being, work and productivity, and health resource use. Further evaluation of alternative epoetin alfa dosing schedules and use of epoetin alfa in treating anemia in patients with specific hematologic malignancies is ongoing.

Topics: Anemia; Clinical Trials as Topic; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Hematologic Neoplasms; Hemoglobins; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Linear Models; Multiple Myeloma; Myelodysplastic Syndromes; Quality of Life; Random Allocation; Recombinant Proteins

We are presenting 20 patients with hepatitis C, who developed anemia on interferon alpha-2b/ribavirin treatment and were treated with recombinant human c alpha. Median age was 43 years (range 25-72). Four patients received previous treatment. Interferon-alpha-2b was given at six million units three times a week to 10 patients and at three million units three times a week to five patients. PEG-interferon-alpha-2b (80-120 mug/week) was given to five patients. The dose of ribavirin was 800-1200 mg/day (19 patients) and 200 mg/day (one patient with renal failure). Duration of an interferon/ribavirin treatment was 6-12 months. Baseline median hemoglobin was 13.3 g/dl (range 12.2-15.8); median hemoglobin nadir: 9.8 g/dl (range 8.4-11.2). On erythropoietin, the hemoglobin increased to median 11.7 g/dl (range 9.6-12.8). The ribavirin dose had been decreased to 800 mg in four patients, to 600 mg in four patients, to 400 mg in one patient. Thirteen patients responded to interferon/ribavirin treatment, six patients (all genotype 1) did not. Of the 13 initial responders 11 had sustained response, one still under treatment and two patients relapsed. In conclusion, in our patients with chronic hepatitis C treated with interferon/ribavirin combination therapy, erythropoietin was beneficial in the treatment of ribavirin-induced anemia.

Topics: Adenosine Triphosphate; Anemia; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Glutathione; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Recombinant Proteins; Reticulocyte Count; Ribavirin

In a multinational trial of anaemic patients with cancer receiving nonplatinum-containing chemotherapy, epoetin-alfa effectively increased haemoglobin levels, reduced red blood cell transfusion requirements, and improved QOL. Although the study was not designed or powered to evaluate survival, a survival trend was noted favouring epoetin-alfa compared with placebo (median survival 17 vs 11 months [p = 0.126]).. To determine the incremental cost utility of epoetin-alfa versus placebo in anaemic patients with stage IV breast cancer from a UK National Health Service perspective.. Patient data regarding transfusions, epoetin-alfa usage, chemotherapy treatment cycles, and adverse events were recorded, with survival follow-up for 12-36 months post-study. Stage IV breast cancer therapy costs were collected by surveying UK oncologists, and utilities for associated health states were from published sources. Costs were in British pounds and year 2000 values. Costs and benefits were jointly determined for the stage IV breast cancer subgroup (n = 55). Incremental cost-utility ratios (ICURs) were calculated assuming a 6% annual discount rate for costs and a 1.5% annual discount rate for benefits. Bootstrap simulations (10,000 iterations) were conducted to account for uncertainty, and sensitivity analyses were conducted to establish robustness.. The ICUR for epoetin-alfa treatment was pounds 8,851 per QALY, with a 99% probability of a positive net benefit in QALYs (net benefit = 0.4805 years of perfect life) and a 94% probability of being acceptable using a threshold ICUR of pounds 30,000/QALY. The main cost drivers distinguishing epoetin-alfa from placebo were the costs of drug and patient care due to increased survival.. The available data suggest a high probability of favourable cost-utility outcomes with epoetin-alfa treatment for anaemia in patients with stage IV breast cancer receiving nonplatinum-containing chemotherapy. Additional studies are warranted.

Topics: Adult; Anemia; Antineoplastic Agents; Breast Neoplasms; Cost-Benefit Analysis; Double-Blind Method; Drug Administration Schedule; Endpoint Determination; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Subcutaneous; Neoplasm Staging; Quality of Life; Recombinant Proteins; Survival Analysis; Time Factors; Treatment Outcome

Patients with anemia undergoing elective joint replacement are often excluded from preoperative autologous donation (PAD). The purpose of this study was to compare the efficacy of preoperative erythropoietin (epoetin alpha) as an adjuvant treatment to PAD versus preoperative erythropoietin alfa alone in patients with mild anemia undergoing major orthopedic surgery.. The study enrolled 75 patients scheduled for total joint arthropalsty of the hip or knee or spinal surgery and with a hemoglobin (Hb) concentration between 10 and 13 g/dL. Group 1 patients were assigned to receive weekly doses of subcutaneous epoetin alpha (40,000 IU) 21, 14, and 7 days before surgery and to participate in the PAD program; group 2 patients were excluded from the PAD program and received 2 doses of epoetin alpha every week over the same period.. Group 1 (n = 39) and group 2 (n = 36) were similar with respect to patient characteristics, biological parameters, and surgical procedures, In group 1, mean preoperative Hb rose fom 12.5 g/dL to 12.8 g/dL, patients received a mean 5.1 doses of epoetin alpha, and they gave a mean 1.9 units of autologus blood and 1 received allogenic blood. In group 30.7% received transfusions of autologous blood and 1 received allogenic blood. In group 2, preoperative Hb increased from 11.7 g/dL to 13.5 g/dL, patients received 3.8 doses of epoetin alpha, and 3 were transfused with allogenic blood (P > 0.05).. Epoetin alpha alone and erythropoietin as a adjuvant to a PAD program are equally effective in reducing allogenic transfusion during hip and knee arthroplasty and spinal column surgery of up to 3 spaces.

Topics: Aged; Aged, 80 and over; Anemia; Blood Transfusion; Blood Transfusion, Autologous; Cohort Studies; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Orthopedic Procedures; Preoperative Care; Recombinant Proteins

Anemia is prevalent in HIV-positive patients despite lower doses of zidovudine used in highly active antiretroviral therapy. Previously, epoetin alfa has been administered 3 times weekly (TIW). We compared the hematologic and quality of life (QOL) effects and tolerability of the more convenient once-weekly (QW) regimen with TIW epoetin alfa in anemic HIV-positive patients.. Two hundred eighty-five anemic (hemoglobin [Hb] <12 g/dL) HIV-positive adults receiving stable antiretroviral therapy were enrolled in this 16-week, randomized, multicenter study. Enrolled patients were randomized to receive epoetin alfa doses of 40,000 to 60,000 U QW or 100 to 300 U/kg TIW.. Two hundred seventy-two patients were evaluable for efficacy. Both epoetin alfa dosing schedules produced significant Hb level increases by week 2 (mean Hb increase of 1.3 g/dL [QW] and 1.0 g/dL [TIW]; P < 0.0001) that continued to increase until week 8 and were maintained until study completion, with no significant difference between treatment groups at final Hb measurement (mean Hb increase of 2.9 g/dL [QW] and 2.5 g/dL [TIW]). All QOL parameters improved significantly (P < 0.05) from baseline by week 8 in both groups, with no significant differences between groups at week 16. Both dosing schedules were well tolerated.. QW dosing of epoetin alfa is as effective as TIW dosing in increasing Hb levels, which was associated with improved QOL in anemic HIV-positive patients. QW dosing should also offer added convenience for patients and caregivers.

Topics: Adult; Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; HIV Infections; HIV-1; Humans; Male; Prospective Studies; Quality of Life; Recombinant Proteins

The aim of this study was to determine the efficacy of epoetin alfa in alleviating anemia and minimizing ribavirin (RBV) dose reductions in patients with chronic hepatitis C virus (HCV) infection receiving combination RBV/interferon alfa (IFN) therapy.. HCV-infected patients who had Hb levels of 12 g/dl or less during the first 24 wk of combination RBV/IFN therapy (n=64) were randomized to treatment with epoetin alfa (40,000 units) s.c. q.w. or to standard of care (SOC) for anemia management (RBV dose reduction or discontinuation, transfusions). Primary and secondary efficacy endpoints were changes in Hb level and RBV dosage, respectively, from baseline to week 16 of epoetin alfa therapy. Based on intent-to-treat analysis, the mean changes from baseline Hb levels at week 16 were +2.8 g/dl for epoetin alfa versus +0.4 g/dl for SOC (p<0.0001), and the mean changes in RBV dosage were -34 mg/day for epoetin alfa versus -146 mg/day (p=0.060) for SOC. The mean Hb level at week 16 in the epoetin alfa group (13.8 g/dl) was significantly (p<0.0001) higher than that of the SOC group (11.4 g/dl). At week 4 and subsequently, significantly more patients in the epoetin alfa group did not have RBV dosage reductions (p<0.011). At study end, 83% of epoetin alfa-treated patients maintained RBV dosages of at least 800 mg/day, compared with 54% of patients receiving SOC (p=0.022). Epoetin alfa was well tolerated.. In anemic HCV-infected patients treated with RBV/IFN, epoetin alfa increases Hb levels and maintains RBV dosing. Based on these results, epoetin alfa seems to be promising in the treatment of HCV treatment-related anemia. Further research is warranted to determine the potential impact on outcomes, including quality of life and sustained viral response rate.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Anemia; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon-alpha; Male; Middle Aged; Probability; Recombinant Proteins; Reference Values; Ribavirin; Treatment Outcome

Quality of life (QOL) endpoints from a randomized, placebo-controlled trial of anemic cancer patients treated with nonplatinum-containing chemotherapy who received epoetin alfa or placebo were subjected to a sensitivity analysis. Three QOL instruments were used: the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Cancer Linear Analog Scale (CLAS), and the Medical Outcomes Study Short Form-36 (SF-36). The seven primary endpoints chosen a priori for analysis were: the Functional Assessment of Cancer Therapy-General (FACT-G) Total, FACT-An fatigue subscale, CLAS energy, CLAS daily activities, CLAS overall QOL, and the SF-36 physical and mental component summary scales. Lower QOL scores were reported for patients who discontinued early, suggesting a nonrandom dropout process. Significant correlations (ranging from 0.37 to 0.77) between individual rates of change and the time to early termination of therapy or death supported this conclusion. Estimates of within-treatment-arm QOL change over time are more conservative with the missing not at random (MNAR) assumption as compared with the more optimistic estimates with the assumption that missing QOL data are missing at random (MAR). However, the between-treatment-arm comparisons were consistent across analyses, demonstrating statistically significant differences in favor of the epoetin alfa arm for four of the seven outcome measures.

Topics: Aged; Anemia; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Recombinant Proteins; Sensitivity and Specificity; Surveys and Questionnaires; Treatment Outcome

Anemia, a commonly occurring morbidity in patients with cancer, often leads to diminished quality of life (QOL). Numerous clinical trials have shown that epoetin alfa treatment improves hematologic and QOL variables in cancer patients. The clinical trial analysis reported here was performed to assess response to epoetin alfa in patients with hematologic malignancies. Cancer patients with anemia undergoing non-platinum-based chemotherapy who were enrolled in a multinational, randomized (2:1), double-blind, placebo-controlled trial were prospectively stratified by tumor type (hematologic, solid). Efficacy endpoints included proportion of patients transfused after day 28; change in hemoglobin (Hb) level from baseline to last assessment; proportion of treatment responders (increase in Hb > or =2 g/dl unrelated to transfusion) and correctors (patients whose Hb levels reached > or =12 g/dl during the study); and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study, and survival for the full study cohort was estimated using Kaplan-Meier techniques. Efficacy analyses of hematologic and QOL variables, as well as Kaplan-Meier estimates of survival, were performed post hoc for the hematologic tumor stratum. Among patients with hematologic malignancies, the mean increase in Hb levels was greater with epoetin alfa than with placebo treatment (2.2 vs. 0.3 g/dl). Transfusion requirements were lower in patients who received epoetin alfa versus placebo (25.2 vs. 43.1%), and the proportion of responders and correctors was higher with epoetin alfa than with placebo (75.2 vs. 16.7% and 72.6 vs. 14.8%, respectively). Patients who received epoetin alfa had improved QOL while patients who received placebo had decreased QOL. These results are similar to those seen in the full study cohort, where differences between epoetin alfa and placebo were significant (P<0.05) for all five primary cancer- and anemia-specific QOL domains evaluated. Although the study was not powered for survival, Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa in both the full study cohort and the hematologic subgroup. Epoetin alfa treatment was well tolerated. Epoetin alfa therapy increased Hb levels, reduced transfusion requirements, and improved QOL in patients with anemia undergoing non-platinum chemotherapy for hematologic malignancies.

Topics: Adult; Anemia; Blood Transfusion; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematologic Neoplasms; Hemoglobins; Humans; Male; Middle Aged; Placebos; Quality of Life; Recombinant Proteins; Survival Analysis

To evaluate the efficacy of perioperative recombinant human erythropoietin (r-HuEPO, epoetin alfa) in stimulating hematopoiesis and reducing allogeneic blood transfusion requirements in major head and neck cancer surgery.. Double-blinded, placebo-controlled, randomized, prospective clinical trial.. Fifty-eight patients undergoing surgical resection of head and neck tumors at the University of Iowa hospitals completed this study. Patients were required to have a pre-study hemoglobin >/=10.0 g/dL and

Topics: Adult; Aged; Aged, 80 and over; Anemia; Blood Loss, Surgical; Blood Transfusion; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Head and Neck Neoplasms; Hematinics; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Recombinant Proteins

The efficacy and safety of epoetin alfa in ameliorating cancer- or chemotherapy-related anemia and reducing red blood cell (RBC) transfusion requirements have been demonstrated in numerous trials in adult patients. However, limited information is available about recombinant human erythropoietin (rHuEPO, epoetin alfa) as a treatment option in pediatric cancer patients.. To gain more information about the efficacy and safety of epoetin alfa in the treatment of chemotherapy-induced anemia in children with solid tumors receiving either platinum- or nonplatinum-containing chemotherapy, an 8-week randomized trial was conducted. Epoetin alfa 150 IU/kg was given 3 times a week for 8 weeks to 17 patients; 17 control patients received standard of care.. Transfusions, administered if the hemoglobin (Hb) level dropped to below 6 g/dL, were necessary for only one patient in the epoetin alfa group, as compared with eight patients in the control group (change in Hb from 8.5-10.21 g/dL in the epoetin alfa group vs. 8.48-8.41 g/dL in the control group).. The data from this study suggest that this dosing regimen of epoetin alfa is effective and safe in pediatric cancer patients with chemotherapy-related anemia. Further studies with epoetin alfa in more children with different chemotherapy regimens are needed.

Topics: Adolescent; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Child; Child, Preschool; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Infant; Injections, Subcutaneous; Male; Neoplasms; Recombinant Proteins; Treatment Outcome

Combination chemotherapy is often used for long periods in children with solid malignancies, leading to anemia and necessitating intervention with red blood cell (RBC) transfusions. Transfusions, however, are associated with a variety of adverse events and risks. Recombinant human erythropoietin (rHuEPO, epoetin alfa) has been shown to reduce the need for transfusions and to ameliorate the symptoms of anemia in adults, but few studies have been conducted thus far in pediatric patients.. Thirty-seven children with solid tumors receiving treatment with platinum- or nonplatinum-based chemotherapy were treated with epoetin alfa and supplemental iron in a single-center, open-label, 28-week, case-control study.. Epoetin alfa significantly reduced the need for RBC (P = 0.007) and platelet (P = 0.01) transfusions, and prolonged the time to first RBC transfusion (P = 0.0004) as compared to the control group. Moreover, epoetin alfa was effective in maintaining mean hemoglobin levels during the course of the study, whereas they declined below baseline after week 9 in the control group.. Epoetin alfa is effective and safe in reducing transfusion requirements and maintaining adequate hemoglobin levels in children with solid tumors undergoing combination chemotherapy.

Topics: Adolescent; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Child; Child, Preschool; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Infant; Injections, Intravenous; Injections, Subcutaneous; Male; Neoplasms; Recombinant Proteins; Treatment Outcome

Hemoglobin increases have been associated with quality of life (QOL) improvements in anemic cancer patients treated with epoetin alfa, but intervention generally has been reserved for symptomatic anemia or hemoglobin < 10 g/dL. Relationships among hemoglobin, functional status, and patient reported QOL have not been well characterized.. Data from two open-label, community-based trials of epoetin alfa therapy that enrolled 4382 anemic cancer patients undergoing chemotherapy were used to evaluate the relationship between hemoglobin changes and QOL changes. The authors measured QOL using the Linear Analog Scale Assessment (LASA) and the more detailed, disease-specific Functional Assessment of Cancer Therapy-Anemia (FACT-An) instrument. Analyses were performed to determine the incremental change in QOL associated with hemoglobin increases (1 g/dL increments).. Cross-sectional analyses showed a nonlinear relationship and significant positive correlation between high hemoglobin levels and high LASA and FACT-An scores (r = 0.25 and 0.29, respectively, P < 0.01). Patients with hemoglobin increases of > or = 2 g/dL reported statistically significant improvements in five FACT-An items selected a priori specifically to reflect functional capacity. An incremental analysis used regression methods to identify the longitudinal relationship between incremental changes in hemoglobin and QOL scores. This relationship was found to be nonlinear, with the maximum QOL gain occurring at a hemoglobin level of 12 g/dL (range, 11-13 g/dL). Patients with low baseline QOL scores and longer time periods between baseline and final QOL assessments experienced significantly (P < 0.05) greater increases in overall QOL. Progressive disease at baseline, change in disease status from baseline to end of study, and increase in self-reported pain or nausea all had significant (P < 0.05) negative effects on QOL scores.. A direct relationship exists between hemoglobin increases during epoetin alfa therapy and corresponding QOL improvements in cancer patients receiving chemotherapy across the clinically relevant hemoglobin range of 8-14 g/dL. These data suggest that the maximal incremental gain in QOL occurs when hemoglobin is in the range of 11-13 g/dL.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Quality of Life; Recombinant Proteins

The objectives of this study were to assess the safety and efficacy of darbepoetin alfa (Aranesp) administered every 2 weeks in anemic patients with solid tumors receiving chemotherapy. This was an open-label, randomized, active-controlled, multicenter dose-finding study evaluating a range of every-2-week darbepoetin alfa doses. The active control arm received epoetin alfa (Epogen, Procrit) at 40,000 U weekly with a dose increase to 60,000 U weekly for subjects with an inadequate response. The lowest clinically effective doses of darbepoetin alfa in this study were 3.0 and 5.0 microg/kg every 2 weeks, with no additional benefit observed at higher doses. The percentage of patients who achieved a hematopoietic response in the 3.0- and 5.0-microg/kg groups was 66% (95% confidence interval [CI] = 46%-86%) and 84% (95% CI = 67%-100%), respectively, compared with 63% (95% CI = 46%-81%) in the epoetin alfa group. Darbepoetin alfa administered at a dose of 3.0 microg/kg every 2 weeks is safe and effective for treating anemia in patients with solid tumors on chemotherapy, and is comparable to epoetin alfa. A dose increase to 5.0 microg/kg of darbepoetin alfa administered every 2 weeks may be appropriate in patients with an inadequate initial response.

Topics: Anemia; Breast Neoplasms; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Gastrointestinal Neoplasms; Genital Neoplasms, Female; Genital Neoplasms, Male; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Recombinant Proteins; Treatment Outcome

The response to epoetin-alpha treatment is hard to predict in cancer patients receiving chemotherapy.. One hundred and seventeen patients were enrolled in this observational study. They had a hemoglobin (Hb) level less than or equal to 10.5 g/dL, were receiving platinum chemotherapy with three cycles pending, and they did not have an iron deficiency or hemolysis. Epoetin-alpha was administered subcutaneously three times a week at a dose of 150 IU/kg. Ninety patients were examined.. Response was defined as an increase in Hb of at least 2 g/dL during the treatment period. The response rate was 63.3%. The following data were compared between responders and nonresponders at the onset of treatment and after 2 and 4 weeks of epoetin therapy: Hb, reticulocytes, serum iron, ferritin, transferrin, transferrin saturation index, and endogenous erythropoietin levels. At baseline, these variables were similar for responders and nonresponders; after 2 weeks, responders showed higher Hb (P = 0.001) and transferrin levels (P = 0.042) and reticulocyte counts (P = 0.003); after 4 weeks, only the Hb level showed a significant difference (P < 0.0005). Changes from baseline in Hb level after 2 and 4 weeks correlated significantly (P < 0.01) with response. The change in Hb level at Week 4 was the best predictor. A change in Hb level of less than 0.5 g/dL was associated with a lack of response (predictive power, 71%); a change in Hb greater than or equal to 0.5 g/dL was associated with response (predictive power, 89%).. Response to epoetin-alpha treatment in cancer patients receiving platinum chemotherapy can be predicted from changes in Hb level after 4 weeks of therapy.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Cisplatin; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Recombinant Proteins; Treatment Outcome

Cancer-related anaemia is associated with a wide spectrum of symptoms that can negatively affect quality of life. Because epoetin alfa has demonstrated efficacy in correcting cancer-related anaemia, the impact of this treatment on quality of life was evaluated in a multinational, randomised, double-blind, placebo-controlled trial in 375 anaemic cancer patients receiving non-platinum-based chemotherapy. The cancer-specific measures of quality of life included the general scale (FACT-G Total) and fatigue subscale (FACT-An Fatigue subscale) of the Functional Assessment of Cancer Therapy-Anaemia and the Cancer Linear Analogue Scales measuring energy, ability to do daily activities, and overall quality of life. These measures were also used to examine the relationship between haemoglobin levels and quality of life. Both univariate and multiple linear regression analyses of quality of life data were performed. Results of the univariate analysis have been reported previously. The a priori-planned multiple linear regression analysis, which accounted for the effects of disease progression and several other possibly confounding variables on quality of life, showed a significant advantage for epoetin alfa over placebo for the five scales (all, P<0.05), and confirmed the results of the univariate analysis. For cancer-specific measures, significant correlations were demonstrated between baseline haemoglobin and quality of life (r, range: 0.14-0.26, all P<0.05) and between change in haemoglobin and change in quality of life (r, range: 0.26-0.34, all P<0.01). These findings provide evidence that increasing haemoglobin levels by epoetin alfa administration can significantly improve cancer patients' quality of life.

Topics: Activities of Daily Living; Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Survival Rate; Treatment Outcome

Topics: Activities of Daily Living; Adolescent; Anemia; Antineoplastic Agents; Blood Transfusion; Double-Blind Method; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Treatment Outcome

The objective of the study was to evaluate and compare the safety and effectiveness of epoetin omega (produced in baby hamster kidney cells) and epoetin alfa (produced in Chinese hamster ovary cells) in sustaining the correction of anemia in maintenance hemodialysis patients. The study, a prospective and controlled crossover, was completed in 38 stable patients treated with both epoetins for 24 weeks. Group A (17 patients) started with epoetin omega, and Group B (21 patients) started with epoetin alfa. After 24 weeks, a 4 week crossover (wash out) was made: Group A was switched to epoetin alfa and group B to epoetin omega for the next test period of 24 weeks. Both epoetins were administered subcutaneously after each dialysis. Doses were adjusted with the aim of maintaining a target hemoglobin level between 10 and 12 g/dl (hematocrit 30% to 35%). The mean weekly dose of epoetin omega/kg body weight (BW) was 67 +/- 43 U. The mean weekly dose of epoetin alfa/kg BW was 86 +/- 53 U. The average of all mean values of hemoglobin (Hb) during treatment with epoetin omega was 11.4 +/- 0.7 g/dl (hematocrit 34 +/- 2%), and during treatment with epoetin alfa was 11.3 +/- 0.7 g/dl (hematocrit 33 +/- 2%) (not significant). Thromboses of vascular access occurred in 3 patients during an epoetin omega treatment and in 3 patients during epoetin alfa treatment. At the site of injection, only 1 patient described a mild pain when treated with epoetin omega and only 6 patients when treated with epoetin alfa. In conclusion, both epoetin omega and epoetin alfa were effective in correcting the anemia of all studied patients. However, lower doses of epoetin omega were needed to maintain the same target hemoglobin level. No serious side effects with either epoetin were noted. The authors believe that additional comparisons of different epoetin preparations should be performed and will provide better insight into their biological activity and clinical responsiveness.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Cross-Over Studies; Epoetin Alfa; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Treatment Outcome

In a single-center, case-control study the authors evaluated the efficacy and safety of epoetin alfa in pediatric cancer patients receiving platinum- or nonplatinum-based chemotherapy. Thirty-seven patients with solid tumors received epoetin alfa 3 times weekly at a dose of 150 IU/kg (hemoglobin [Hb] > or = 12 g/dL and < or = 16 g/dL) or 300 IU/kg (Hb) < 12 g/dL) for 28 weeks. Data from treated patients were compared to data from 37 untreated control patients. Significant between-group differences in favor of the epoetin alfa-treated Patients were observed in overall red blood cell transfusion requirements (p = .007) and overall platelet transfusion requirements (p = .010). Additionally, significant between-group differences favoring epoetin alfa were seen by Kaplan-Meier plots, estimating mean time to first red blood cell transfusion (p = .0004). Mean Hb (g/dL) was maintained at baseline levels in the epoetin alfa group for most of the course of the study. No drug-related adverse events were seen in epoetin alfa-treated patients.

Topics: Adolescent; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Case-Control Studies; Child; Child, Preschool; Drug Interactions; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Infant; Male; Neoplasms; Platinum Compounds; Recombinant Proteins; Therapeutic Equivalency; Time Factors

Data from two large, community-based clinical trials that evaluated the efficacy of epoetin alfa in anemic cancer patients receiving chemotherapy were retrospectively analyzed to determine if clinical outcomes were different depending on whether chemotherapy was platinum- or nonplatinum-based.. Patients received epoetin alfa 150-300 IU/kg (Glaspy: Study 1; n = 2,342) or 10,000-20,000 IU (Demetri: Study 2; n = 2,370) s.c. three times each week for 4 months. Efficacy end points were changes in transfusion requirements, hemoglobin (Hb) levels, and quality of life (QOL). A total of 4,298 out of 4,712 patients (platinum-based, n = 1,601; nonplatinum-based, n = 2,697), who both received chemotherapy and had available data, were eligible for this retrospective analysis.. Baseline characteristics across groups were comparable with few exceptions, which were anticipated in view of the characteristics of the two different chemotherapy types. Decreases in transfusion requirements after 2, 3, and 4 months were significant, regardless of chemotherapy type. Mean increases in Hb level from baseline to final evaluation ranged from 1.6 g/dl to 2.0 g/dl across study groups and were significant, regardless of chemotherapy type. QOL, as measured by the Linear Analog Scale Assessment (LASA), improved significantly by 20%-43%, regardless of chemotherapy type, and improvements were associated with increases in Hb. Epoetin alfa was well tolerated in both studies, regardless of chemotherapy type.. Treatment of anemic cancer patients with epoetin alfa results in significant reduction in transfusion requirements, increase in Hb levels, and improvements in QOL, regardless of whether the chemotherapy is platinum- or nonplatinum-based.

Topics: Anemia; Blood Transfusion; Disease Progression; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hematologic Neoplasms; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Platinum; Predictive Value of Tests; Prognosis; Quality of Life; Recombinant Proteins; Retrospective Studies; Sensitivity and Specificity; Time Factors; Treatment Outcome

A controlled clinical trial was conducted to evaluate the use of epoetin alfa in cachectic patients with solid tumors who were not receiving chemotherapy to determine if increasing hemoglobin (Hb) resulted in increased exercise capacity, metabolism, and energy efficiency during a maximum work load. The randomized, prospective study included 108 patients who received oral indomethacin 50 mg twice daily (n = 58; control group), or oral indomethacin 50 mg twice daily with epoetin alfa 4,000 to 10,000 IU by subcutaneous injection 3 times weekly (n = 50; study group). Patients randomized to the study group received epoetin alfa only when Hb decreased below 12.8 g/dL for men and 12.0 g/dL for women. Mean Hb levels in the study group were significantly (P <.0001) improved overall compared with the control group, with significant differences seen between groups after 2 to 4 months (P <.003), 6 to 8 months (P <.01), and 10 to 30 months (P <.01). Mean inflammatory variables including serum albumin, erythrocyte sedimentation rate, and C-reactive protein were significantly (P <.02) changed in the study group compared with the control group (ie, the control group had more inflammation). Significantly lower mean body weight (P <.05) and resting energy expenditure (P <.007) were recorded for patients in the control group versus the study group. The study group showed significantly greater mean exercise capacity (P <.0001), mean oxygen uptake (P <.01), mean CO(2) production (P <.009), and respiration (P <.03). These results demonstrate that early use of epoetin alfa prevents anemia in patients with progressive cancer who are not receiving chemotherapy. Normalization of Hb levels resulted in improved whole-body metabolism and energy efficiency, which is associated with greater exercise capacity and better daily quality of life.

Topics: Aged; Anemia; Anti-Inflammatory Agents, Non-Steroidal; Cachexia; Cyclooxygenase Inhibitors; Energy Metabolism; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Indomethacin; Male; Middle Aged; Neoplasms; Physical Exertion; Prospective Studies; Quality of Life; Recombinant Proteins

A prospective open-label study was designed to evaluate the safety, efficacy, and impact on quality of life of recombinant human erythropoietin (rHuEPO, epoetin alfa) therapy for cancer-related anemia. Of the 401 patients enrolled at 34 centers from across Canada, a cohort of 183 patients did not receive chemotherapy during the 16-week study period. All patients received epoetin alfa 150 IU/kg subcutaneously 3 times per week. The dose was increased to 300 IU/kg if the hemoglobin level did not increase by at least 1.0 g/dL after 4 weeks. Epoetin alfa therapy significantly increased hemoglobin levels and reduced transfusion requirements. Moreover, epoetin alfa provided statistically significant and clinically meaningful improvements in quality of life as measured by the Functional Assessment of Cancer Therapy-Anemia and Linear Analog Scale Assessment (also known as Cancer Linear Analog Scale). Increases in hemoglobin were correlated significantly with improvements in quality of life as well as Eastern Cooperative Oncology Group performance status. Treatment with epoetin alfa was well tolerated. These results demonstrate that epoetin alfa therapy is effective and safe in cancer patients with anemia, regardless of whether they are or are not receiving chemotherapy.

Topics: Aged; Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Sickness Impact Profile

Darbepoetin alfa (Aranesp; Amgen, Thousand Oaks, CA) is a new erythropoiesis-stimulating protein with a threefold longer terminal half-life than recombinant human erythropoietin (epoetin) in patients with chronic kidney disease (CKD). The purpose of this randomized, double-blind, noninferiority study is to determine whether darbepoetin alfa is as effective as epoetin for the treatment of anemia in hemodialysis patients when administered at a reduced dosing frequency.. Patients receiving epoetin therapy were randomized to continue epoetin administered intravenously (IV) three times weekly (n = 338) or change to darbepoetin alfa administered IV once weekly (n = 169). The dose of darbepoetin alfa or epoetin was individually titrated to maintain hemoglobin concentrations within -1.0 to +1.5 g/dL (-10 to +15 g/L) of patients' baseline values and within a range of 9.0 to 13.0 g/dL (90 to 130 g/L) for up to 28 weeks (20-week dose-titration period followed by an 8-week evaluation period). The primary end point was change in hemoglobin level between baseline and the evaluation period (weeks 21 to 28).. Mean changes in hemoglobin levels from baseline to the evaluation period were 0.24 +/- 0.10 (SE) g/dL (2.4 +/- 1.0 g/L) in the darbepoetin alfa group and 0.11 +/- 0.07 g/dL (1.1 +/- 0.7 g/L) in the epoetin group, a difference of 0.13 g/dL (95% confidence interval [CI], -0.08 +/- 0.33 [1.3 g/L; 95% CI, -0.8 to 3.3]). This difference was not statistically significant or clinically relevant despite the reduced frequency of darbepoetin alfa administration. The safety profile of darbepoetin alfa was similar to that of epoetin, and no antibody formation to either treatment was detected.. These results show that darbepoetin alfa maintains hemoglobin concentrations as effectively and safely as epoetin in patients with CKD, but with a reduced dosing frequency.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Canada; Darbepoetin alfa; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Humans; Injections, Intravenous; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Treatment Outcome; United States

Effects of epoetin alfa on transfusions, haemoglobin (Hb) and quality of life (QOL) were evaluated in a placebo-controlled study of 145 patients with multiple myeloma and anaemia (Hb < 11 g/dl). During the 12-week, double-blind phase, patients received 150 IU/kg epoetin alfa or a matching volume of placebo subcutaneously three times weekly; the dose (or volume) was doubled at week 4 if Hb response was inadequate. Patients completing this phase could enter the subsequent optional 12-week phase of open-label epoetin alfa treatment. During double-blind treatment, epoetin alfa significantly decreased the incidence of transfusion compared with placebo (28% vs. 47%, P = 0.017), regardless of patients' transfusion history, and increased mean Hb (1.8 g/dl vs. 0.0 g/dl, P < 0.001). Univariate analysis showed significant (P

Topics: Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Lipoxygenase Inhibitors; Male; Middle Aged; Multiple Myeloma; Quality of Life; Recombinant Proteins

This randomized, double-blind, placebo-controlled clinical trial assessed the effects of epoetin alfa on transfusion requirements, hematopoietic parameters, quality of life (QOL), and safety in anemic cancer patients receiving nonplatinum chemotherapy. The study also explored a possible relationship between increased hemoglobin and survival.. Three hundred seventy-five patients with solid or nonmyeloid hematologic malignancies and hemoglobin levels < or = 10.5 g/dL, or greater than 10.5 g/dL but < or = 12.0 g/dL after a hemoglobin decrease of > or = 1.5 g/dL per cycle since starting chemotherapy, were randomized 2:1 to epoetin alfa 150 to 300 IU/kg (n = 251) or placebo (n = 124) three times per week subcutaneously for 12 to 24 weeks. The primary end point was proportion of patients transfused; secondary end points were change in hemoglobin and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study.. Epoetin alfa, compared with placebo, significantly decreased transfusion requirements (P =.0057) and increased hemoglobin (P <.001). Improvement of all primary cancer- and anemia-specific QOL domains, including energy level, ability to do daily activities, and fatigue, was significantly (P <.01) greater for epoetin alfa versus placebo patients. Although the study was not powered for survival as an end point, Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa (P =.13, log-rank test), and Cox regression analysis showed an estimated hazards ratio of 1.309 (P =.052) favoring epoetin alfa. Adverse events were comparable between groups.. Epoetin alfa safely and effectively ameliorates anemia and significantly improves QOL in cancer patients receiving nonplatinum chemotherapy. Encouraging results regarding increased survival warrant another trial designed to confirm these findings.

Topics: Activities of Daily Living; Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Transfusion; Double-Blind Method; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Recombinant Proteins; Survival Analysis; Treatment Outcome

To prospectively evaluate the effectiveness, safety, and clinical benefits of once-weekly epoetin alfa therapy as an adjunct to chemotherapy in anemic cancer patients.. A total of 3,012 patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this multicenter, open-label, nonrandomized study conducted in 600 United States community-based practices. Patients received epoetin alfa 40,000 U once weekly, which could be increased to 60,000 U once weekly after 4 weeks dependent on hemoglobin response. Treatment was continued for a maximum of 16 weeks.. Among the 2,964 patients assessable for efficacy, epoetin alfa therapy resulted in significant increases in hemoglobin levels, decreases in transfusion requirements, and improvements in functional status and fatigue as assessed by the linear analog scale assessment (energy level, ability to perform daily activities, and overall quality of life) and the anemia subscale of the Functional Assessment of Cancer Therapy-Anemia questionnaire. Improvements in quality-of-life parameters correlated significantly (P <.001) with increased hemoglobin levels. The direct relationship between hemoglobin and quality-of-life improvement was sustained during the 16-week study period, which is similar to findings of large community-based trials of three-times-weekly dosing. Once-weekly epoetin alfa was well tolerated, with most adverse events attributed to the underlying disease or concomitant chemotherapy.. The results from this large, prospective, community-based trial suggest that once-weekly epoetin alfa therapy increases hemoglobin levels, decreases transfusion requirements, and improves quality of life in patients with cancer and anemia who undergo concomitant chemotherapy. Based on the results of this study, the clinical benefits and the adverse event profile of once-weekly epoetin alfa therapy in community-based practice are similar to those observed in the historical experience with the three-times-weekly dosage schedule.

Topics: Activities of Daily Living; Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Transfusion; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Treatment Outcome

To compare the pharmacokinetics, pharmacodynamics, and tolerance of epoetin alfa administered subcutaneously (s.c.) once weekly (q.w.) and three times weekly (t.i.w.).. An open-label, randomized, parallel-design study was conducted in 36 healthy adults with hemoglobin (Hb) levels of 11.7 14.0 g/dl for women and 13.0-14.8 g/dl for men. Subjects were randomized to epoetin alfa 150 IU/kg s.c. t.i.w. or 40,000 IU s.c. q.w. for 4 weeks. Serum erythropoietin concentrations were measured using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetic parameters [peak serum concentration (Cmax), mean predose trough concentration (Cmin), time to Cmax (tmax), clearance after s.c. administration (CL/F), area under the plasma concentration time curve (AUC), and terminal elimination half-life (t 1/2)] were calculated using model-independent methods. Mean changes from baseline and AUC of percentage reticulocytes, Hb, and total red blood cell (RBC) concentrations over the 1-month study period were calculated.. The Cmax values for serum epoetin alfa q.w. were six times and AUC(0-168) values three times that of the t.i.w. regimen. Time profiles of changes in percentage reticulocytes, Hb, and total RBC over 1 month were similar between regimens. The rate of increase in Hb was similar for the two groups, and both groups exhibited a 3.1-g/dl increase in mean Hb levels from baseline through day 29. Changes in ferritin levels were generally similar between groups and reflected expected use of iron stores for Hb production. Epoetin alfa administered t.i.w. or q.w. was well tolerated and no serious adverse events occurred.. The pharmacodynamic responses were equivalent between groups despite expected differences in total erythropoietin exposure. These results indicate that the epoetin alfa 150 IU/kg t.i.w. and 40,000 IU q.w. regimens can be considered clinically equivalent.

Topics: Adolescent; Adult; Anemia; Area Under Curve; Biological Availability; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Epoetin Alfa; Erythrocyte Count; Erythropoietin; Female; Half-Life; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Male; Recombinant Proteins; Reticulocyte Count

To evaluate efficacy, safety, and quality of life (QOL) changes with epoetin alfa therapy for anemia in patients with nonmyeloid malignancies.. Anemic cancer patients were enrolled onto this prospective, open-label study from 34 centers across Canada. The trial had two cohorts: patients who were and were not receiving chemotherapy during the 16-week study. All patients initially received epoetin alfa 150 IU/kg subcutaneously three times per week. The dose was doubled after 4 weeks for patients who did not experience sufficient response.. Of the 183 patients enrolled in the nonchemotherapy cohort, statistically significant and clinically relevant improvements in QOL were observed with epoetin alfa therapy using both the FACT-An questionnaire and linear analog scale assessment. Hemoglobin levels increased significantly (P <.001; mean increase 2.5 g/dL from baseline to end of study) and these increases were positively correlated with improved QOL and change in Eastern Cooperative Oncology Group (ECOG) scores. There was a significant reduction in the percentage of patients who required blood transfusions. The 218 patients in the chemotherapy cohort also experienced significant improvements in QOL, decreased transfusion use, and increased hemoglobin levels that correlated with QOL improvements and change in ECOG scores. Epoetin alfa was well-tolerated in both cohorts.. Epoetin alfa administered to patients with cancer-related anemia for up to 16 weeks resulted in significantly improved QOL, increased hemoglobin levels, and decreased transfusion use. These benefits were observed in cancer patients who were not receiving chemotherapy as well as those who were.

Topics: Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Health Status Indicators; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins

This randomized, placebo-controlled trial was designed to assess the efficacy and safety of therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (epoetin alfa) in anemic, neutropenic patients with myelodysplastic syndrome. Sixty-six patients were enrolled according to the following French-American-British classification: refractory anemia (20), refractory anemia with excess blasts (35), refractory anemia with ringed sideroblasts (9), and refractory anemia with excess blasts in transformation (2). Patients were stratified by their serum erythropoietin levels (less than or equal to 500 mU/mL, n = 37; greater than 500 mU/mL, n = 29) and randomized, in a 2:1 ratio, to either GM-CSF (0.3-5.0 microg/kg.d) + epoetin alfa (150 IU/kg 3 times/wk) or GM-CSF (0.3-5.0 microg/kg.d) + placebo (3 times/wk). The mean neutrophil count rose from 948 to 3831 during treatment with GM-CSF +/- epoetin alfa. Hemoglobin response (increase greater than or equal to 2 g/dL, unrelated to transfusion) occurred in 4 of 45 (9%) patients in the GM-CSF + epoetin alfa group compared with 1 of 21 (5%) patients with GM-CSF + placebo group (P = NS). Percentages of patients in the epoetin alfa and the placebo groups requiring transfusions of red blood cells were 60% and 92%, respectively, for the low-endogenous erythropoietin patients and 95% and 89% for the high-endogenous erythropoietin patients (P = NS). Similarly, the average numbers of units of red blood cells transfused during the 12-week study in the epoetin alfa and the placebo groups were 5.9 and 9.5, respectively, in the low-endogenous erythropoietin patients and 9.7 and 8.6 in the high-endogenous erythropoietin patients (P = NS). GM-CSF +/- epoetin alfa had no effect on mean platelet count. Treatment was well tolerated in most patients, though 10 withdrew from the study for reasons related predominantly to GM-CSF toxicity. (Blood. 2000;95:1175-1179)

Topics: Anemia; Blood Transfusion; Double-Blind Method; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Neutropenia; Placebos; Recombinant Proteins

Transient ST-segment depression measured on ambulatory ECG monitors has been described as representing silent ischemia. Patients who demonstrate silent ischemia have been reported to show increased mortality compared to patients without silent ischemia. We undertook this study to determine if the correction of anemia in End Stage Renal Disease (ESRD) patients from (+/- = standard deviation) 30 +/- 3 to 42 +/- 3 with the use of Epoietin alfa would result in decreased silent ischemia in patients with clinically evident ischemic heart disease or congestive heart failure.. Thirty one ESRD patients with congestive heart failure or patients with clinically-evident ischemic heart disease were randomized into one of two arms. Patients in Group A had their hematocrit increased with the use of slowly escalating doses of Epoietin alfa to 42 +/- 3% and patients in Group B were maintained with a hematocrit of 30 +/- 3% throughout the course of the study. All patients had a 24 hour Holter monitor recording at baseline and at 28 weeks after randomization (when they had reached their target hematocrit). Significant silent ischemia was considered to be present if patients demonstrated at least 60 seconds of > or = 1 mm ST segment depression.. Fifteen patients were randomized to Group A and 16 patients were randomized to Group B. The mean hematocrit increased in group A from 29.1 +/- 2.4% to 40.8 +/- 5.2% after 30 weeks. The mean hematocrit in Group B remained stable at 30 +/- 3% throughout the course of the study. Ten patients demonstrated silent ischemia at baseline. At follow up patients in group A demonstrated a mean of 1.7 +/- 4.9 minutes of ischemia compared to 1.1 +/- 3.4 minutes in group B. These were not significantly different. A similar number of patients in group A and Group B required adjustments in their anti-anginal medication during the course of the study.. It is possible to increase hematocrit to near normal levels in hemodialysis with the administration of exogenous Epoietin alfa. The increase in hematocrit form 30 +/- 3% to 42 +/- 3% is not associated with a change in the level of silent ischemia these patients demonstrate.

Topics: Anemia; Electrocardiography; Electrocardiography, Ambulatory; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Hematinics; Hematocrit; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Ischemia; Prognosis; Recombinant Proteins; Renal Dialysis

Angiotensin-converting enzyme (ACE) inhibitors may exacerbate anemia in patients with chronic renal failure, as well as in dialysis patients. To better answer this question, a prospective, crossover study was conducted to evaluate the effect of ACE inhibitors on recombinant human erythropoietin (rHuEPO) requirements in hemodialysis patients. Patients administered an ACE inhibitor when entering the study remained on this drug for the initial 4 months and were then switched to another antihypertensive agent for 4 more months. Patients not initially administered an ACE inhibitor were switched to lisinopril at 4 months. rHuEPO doses were adjusted using a sliding scale based on weekly laboratory hematocrit values. The inclusion criteria were met by 51 patients undergoing dialysis. Demographics were as follows: 61% were women, 64% were black, 46% had diabetes, average age was 53.2 +/- 13.3 years, and time on hemodialysis was 38.0 +/- 44.5 months. Thirty-three patients completed the study. Hematocrit averaged 32.7% +/- 1.9% while on ACE inhibitor therapy and 33.1% +/- 2.1% off ACE inhibitor therapy (P = 0.217). There was no difference in rHuEPO dose per treatment during each period (3,500 +/- 1,549 U on ACE inhibitor therapy versus 3,312 +/- 1,492 U off ACE inhibitor therapy; P = 0.300). No significant differences were found in degree of blood pressure control or various clinical and laboratory parameters that might be associated with rHuEPO resistance between the two periods. Similarly, no differences were found in hospitalization days, duration of infections, or transfusion requirements. These findings suggest that ACE inhibitors do not contribute to rHuEPO resistance in hemodialysis patients.

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Blood Transfusion; Cross-Over Studies; Diabetes Complications; Drug Resistance; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hematocrit; Hospitalization; Humans; Infections; Kidney Failure, Chronic; Lisinopril; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Time Factors

Since the earliest reports of the use of Epoetin alfa in hemodialysis patients, it has been described that Epoetin alfa may exacerbate preexisting hypertension or induce hypertension in End Stage Renal Disease (ESRD) patients not previously hypertensive. We undertook this study to determine if the correction of anemia in ESRD patients with cardiac disease from a hematocrit of 30+/-3% to 42+/-3% with the use of Epoetin alfa would result in increased blood pressure. This study was a substudy of the "Normal hematocrit Study".. Thirty-one patients were randomized into one of two arms. Patients in Group A had their hematocrit increased with the use of slowly escalating doses of Epoetin alfa to 42+/-3% and patients in Group B were maintained with a hematocrit of 30+/-3% throughout the course of the study. All patients had their blood pressure recorded with a 24 hour ambulatory BP device at study entry and at 28 weeks following randomization when they had achieved their target hematocrit. Pre-dialysis systolic and diastolic BP was also recorded.. The mean hematocrit increased in Group A from 29.1+/-2.4% to 40.8+/-5.2% after 30 weeks. The hematocrit in Group B remained stable at 30+/-3% throughout the course of the study. There was no difference in mean daytime, mean nighttime or 24 hour systolic or diastolic blood pressure between Groups A and B at either baseline or follow-up. Neither was there a difference in mean pre-dialysis systolic or diastolic BP between Groups A or B at baseline or Follow-up. Four patients in Group A and 4 patients in Group B required an increase in their antihypertensive medication during the course of the study.. It is possible to increase hematocrit to normal levels in hemodialysis with the administration of Epoetin alfa. The increase in hematocrit from 30+/-3% to 42+/-3% is not associated with increased blood pressure.

Topics: Adult; Aged; Anemia; Blood Pressure Monitoring, Ambulatory; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hematocrit; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Ischemia; Recombinant Proteins; Reference Values; Renal Dialysis; Treatment Outcome

To evaluate the effect of epoetin alfa on the quality of life (QOL) of HIV-infected patients in the community setting, 221 anaemic (haemoglobin < or = 11 g/dl) HIV-positive patients from community-based treatment centres and physicians' offices were treated with epoetin alfa (100-300 units/kg subcutaneously 3 times a week) in a 4-month, open-label, non-randomized, phase IV trial. Epoetin alfa therapy significantly (P<0.01) increased and maintained haemoglobin levels (mean increase=2.5 g/dl; n=207); the improvement in haemoglobin levels was independent of changes in CD4+ cell counts. Transfusion requirements were also significantly reduced from 20% to 5% of patients (P<0.01). Mean total QOL score measured by the Functional Assessment of HIV Infection (FAHI) scale and Physical Well-Being subscale score improved significantly (P<0.05). QOL improvements associated with increases in haemoglobin were independent of changes in CD4+ counts and baseline anaemia severity. Adverse events observed during epoetin alfa therapy were consistent with HIV disease and not likely due to the drug. Epoetin alfa therapy should be considered a treatment option for HIV-infected patients with mild-to-moderate anaemia.

Topics: Adult; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; HIV Infections; Humans; Male; Quality of Life; Recombinant Proteins

A multicenter, randomized, open-label, parallel-group study was conducted to compare the safety and efficacy of perioperative recombinant human erythropoietin (Epoetin alfa) with the safety and efficacy of preoperative autologous donation (PAD) in total joint arthroplasty. A total of 490 patients scheduled for total joint (i.e., hip or knee) surgery and having hemoglobin (Hb) levels > or = 11 to < or = 13 g/dL were randomized to receive weekly doses of subcutaneous Epoetin alfa on preoperative Days -21, -14, and -7, and on the day of surgery, or to participate in a PAD program. The mean baseline Hb level in both groups was 12.3+/-0.6 g/dL, increasing to 13.8 g/dL in the Epoetin alfa-treated group and decreasing to 11.1 g/dL in the PAD group before or on the day of surgery. In the PAD group, 156/219 (71.2%) patients were transfused with autologous blood, and 42/219 (19.2%) patients were transfused with allogeneic blood. A smaller proportion, 27/209 (12.9%) patients, in the Epoetin alfa-treated group were transfused with allogeneic blood (P = .078 compared with the PAD group). Moreover, patients in the PAD group received a total of 325 units of blood (79 allogeneic units and 246 autologous units) compared with patients in the Epoetin alfa group who received a total of 54 units of blood. The mean postoperative Hb level was 11.0 g/dL in the Epoetin alfa-treated group and 9.2 g/dL in the PAD group. Compared with the PAD arm, mean Hb levels measured preoperatively, postoperatively on Day 1, and at discharge visits were significantly greater in the Epoetin alfa-treated arm (P < .0001 ).

Topics: Age Factors; Anemia; Arthroplasty, Replacement; Blood Loss, Surgical; Blood Transfusion; Blood Transfusion, Autologous; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Postoperative Complications; Prospective Studies; Recombinant Proteins; Sex Factors

To determine the effects of different haemoglobin (Hb) levels on exercise performance and associated electrolyte changes, a prospective, randomized, double-blinded crossover study was completed in 14 haemodialysis patients.. Performance and changes in arterial [K+] and lactate were compared at rest and during a maximal incremental cycling exercise at a Hb concentration ([Hb]) of 10 g/dl ([Hb]10) and 14 g/dl ([Hb]14) following an initial baseline test (Hb: 8.3 +/- 0.2 g/dl, mean +/- SEM). Ages ranged from 23 to 65 years and patients were divided into younger (age 23-45 years, n = 9) and older (aged 55-65 years, n = 5) groups.. Peak work rate and VO2 peak were higher at [Hb]14 than at [Hb]10. 145 +/- 9 vs 134 +/- 9 W, mu +/- SEM, P < 0.01, and 1.90 +/- 0.11 vs 1.61 +/- 0.11 l/min, P < 0.01, respectively. Improvements were demonstrated in both younger and older groups at the higher target [Hb], with an improved aerobic performance evident particularly in younger patients. However, performance remained below that predicted for comparable sedentary controls. Resting plasma [K+] was raised at both [Hb]10 and [Hb]14 compared with baseline (P < 0.01) although the change in [K+] from rest to peak exercise (delta[K+]) was similar at each level. The delta[K+] per unit work performed (used as a marker of K+ regulation) was, however, inversely related to the [Hb] (baseline: 80 +/- 12 micromol/l/kJ vs [Hb]10, 61 +/- 8, P < 0.01, vs [Hb]14. 49 +/- 7, P < 0.05). Exercise induced a significant but similar rise in lactate concentration at both target [Hb] (P < 0.001), which remained markedly elevated for at least 10 min after exercise in both younger and older groups.. These data demonstrate that a physiological [Hb] improves, but does not normalize, exercise performance in end-stage renal failure. Both younger and older patients appear to benefit similarly from the enhanced oxygen transport. Impaired K+ regulation is apparently related to [Hb] and could well contribute to the observed limitations in performance.

Topics: Adult; Aged; Anemia; Blood Volume; Cross-Over Studies; Double-Blind Method; Epoetin Alfa; Erythropoietin; Exercise; Exercise Test; Hemoglobins; Humans; Kidney Failure, Chronic; Middle Aged; Plasma Volume; Potassium; Prospective Studies; Recombinant Proteins; Renal Dialysis

Anaemia commonly occurs in cancer patients receiving chemotherapy, often necessitating blood transfusion. This multicentre study was designed to evaluate the efficacy and safety of epoetin alpha in preventing the decline in haemoglobin (Hb) level, and to determine whether the transfusion requirement could be reduced, in patients receiving 4-6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer (SCLC). A total of 130 non-anaemic SCLC patients were randomized to receive no additional treatment (n = 44), epoetin alpha 150 IU kg(-1) subcutaneously (s.c.) three times a week (n = 42) or 300 IU kg(-1) s.c. three times a week (n = 44). Reductions in epoetin alpha dosage were made during the study if Hb level increased to >15 g dl(-1). The mean weekly dosage was 335 and 612 IU kg(-1), respectively, in the two active treatment groups. Significantly fewer (P < 0.05) epoetin alpha-treated patients experienced anaemia (Hb < 10 g dl(-1)) during the course of chemotherapy (300 IU kg(-1), 39%; 150 IU kg(-1), 48%; untreated, 66%). This was reflected in the significantly lower number of treated patients transfused [300 IU kg(-1), 20% (P< 0.001); 150 IU kg(-1), 45% (P< 0.05); untreated, 59%]. Epoetin alpha was well-tolerated, and there was no evidence of sustained, clinically significant, hypertension. In summary, epoetin alpha is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Cisplatin; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Quality of Life; Recombinant Proteins

Patients may complain of pain at the injection site after subcutaneous (s.c.) administration of erythropoietin (EPO). Local pain due to s.c. EPO into the thigh was evaluated in 60 hemodialysis patients in a double-blind, placebo-controlled study. Identical volumes and concentrations (2000 IU in 0.5 ml) of phosphate-buffered epoetin-alpha (EPO-alpha ph), citrate-buffered epoetin-alpha (EPO-alpha ci) and epoetin-beta (EPO-beta) were compared to 0.5 ml of 0.9% saline (SAL), used as placebo. The patients received the 4 injections at the same occasion. For pain evaluation, a verbal scale ranging from no pain (0) to extremely painful (5) and a 10 cm ungraduated visual analogue score (VAS) (0 = no pain, 10 = maximal pain) were used. Treatment acceptance was assessed (yes/no) and expressed as a percentage of the population. Ranking of the preparations from 1 to 4 according to increasing local discomfort was performed. Median verbal pain scores and interquartile ranges were 1.0 (0-2) for SAL, 0.0 (0-2) for EPO-beta, 1.5 (0-3) for EPO-alpha ph (p < or = 0.05 vs SAL and EPO-beta) and 3.0 (2-4) for EPO-alpha ci (p < or = 0.001 vs EPO-alpha ph). VAS was 0.9 (0.5-2.5) for SAL, 0.9 (0.4-2.4) for EPO-beta, 2.7 (0.8-5.7) for EPO-alpha ph (p < or = 0.001 vs SAL and EPO-beta) and 4.2 (1.7-6.4) for EPO-alpha ci (p < or = 0.001 vs EPO-alpha ph). Treatment acceptance was 73% for SAL, 78% for EPO-beta, 60% for EPO-alpha ph (p < or = 0.05 vs EPO-beta) and 32% for EPO-alpha ci (p < or = 0.05 vs EPO-alpha ph). Ranking was 2 (1-3) for SAL, 2 (1-2) for EPO-beta, 3 (1-4) for EPO-alpha ph (p < or = 0.05 vs SAL and EPO-beta) and 4 (3-4) for EPO-alpha ci (p < or = 0.05 vs SAL and EPO-beta) and 4 (3-4) for EPO-alpha ci (p < or = 0.001 vs EPO-alpha ph). In conclusion, s.c. EPO-alpha ph is better accepted than s.c. EPO-alpha ci. However, s.c. EPO-beta is less painful.

Topics: Aged; Anemia; Buffers; Citrates; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Humans; Injections, Subcutaneous; Male; Pain; Pain Measurement; Patient Acceptance of Health Care; Phosphates; Recombinant Proteins; Renal Dialysis

To identify and treat a unique form of anemia in patients with long-term IDDM.. Patients with IDDM, unexplained symptomatic anemia, and serum creatinine levels of < 177 mumol/l (2.0 mg/dl) were treated with epoetin alfa (Procrit, Ortho Biotech, Raritan, NJ), 50 U/kg three times weekly, subcutaneously, to reach a target hematocrit of 38-40%. Baseline serum erythropoietin titers were measured before drug therapy.. Six patients were treated with epoetin alfa. Median age of the group was 74 years, with IDDM being diagnosed for a median of > 20 years. All patients had symptoms of anemia with a median hematocrit of 28.9% (range 27-31). Compared with iron deficiency control patients, the group had a limited erythropoietin (EPO) response to the degree of anemia. All patients showed increases in hematocrit, median peak of 40.9%, with median time-to-peak response of 12 weeks. Baseline symptoms of anemia resolved in all patients. No adverse effects were noted during the treatment period.. There is a unique form of anemia in patients with long-term IDDM and clinically normal renal function who respond to low-dose epoetin alfa therapy. The rapid response to therapy and depressed baseline erythropoietin titers suggest the anemia is due to a lack of endogenous EPO release.

Topics: Aged; Aged, 80 and over; Anemia; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Glycated Hemoglobin; Hematinics; Hematocrit; Humans; Male; Middle Aged; Potassium; Recombinant Proteins; Treatment Outcome

Patients with cancer have inappropriately low levels of endogenous erythropoietin for the degree of anemia and further suppression of erythropoiesis results from chemotherapy. Patients with lung cancer, in particular, require a high frequency of transfusions, as they are unable to tolerate the symptoms of anemia due to their underlying pulmonary disease and, often, their age. Data from phase I and II trials indicated that epoetin alfa could increase hemoglobin concentration and reduce transfusion requirements. The beneficial response was dose dependent. These findings were confirmed in a series of three double-blind, placebo-controlled, multicenter phase III trials. Clinical trial evidence indicates that 150 IU/kg epoetin alfa three times weekly effectively treats anemia and decreases transfusion requirements in most cancer patients after the first month of chemotherapy. Furthermore, epoetin alfa will reduce the degree of anemia and markedly reduce the need for transfusions, thereby preventing anemia in patients undergoing multiple cycles of platinum-based combination chemotherapy. Epoetin alfa is well tolerated and shows marked activity in preventing anemia and reducing blood transfusion requirements in patients undergoing cyclic chemotherapy.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Anemia is common in patients infected with the human immunodeficiency virus (HIV). The etiology is often multifactorial and may include the HIV infection itself, opportunistic infections, cancer, medications (particularly zidovudine and sulfa-containing drugs), or anemia of chronic disease. Epoetin alfa therapy may play a supportive role in some HIV-infected patients by increasing hemoglobin, decreasing fatigue, and reducing the need for exposure to red blood cell transfusions. A large, placebo-controlled trial in the United States for anemic patients with the acquired immunodeficiency syndrome taking zidovudine demonstrated a statistically significant improvement in hematocrit in patients treated with epoetin alfa compared with placebo. Transfusion requirements decreased in epoetin alfa-treated patients over a 3-month period compared with placebo with a trend toward improvement in quality of life. Epoetin alfa was effective, however, only in patients whose pretreatment erythropoietin levels were less than 500 mU/mL. These advantages of epoetin alfa treatment may become especially important as HIV becomes more of a chronic disease, with the concern that red blood cell transfusion may accelerate progression of HIV.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Blood Transfusion; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins

Anemia is a frequent complication of multiple myeloma, becoming chronic in patients who are resistant to chemotherapy. This randomized, parallel, controlled multicenter study (71 patients receiving concomitant chemotherapy) evaluated the efficacy and safety of epoetin alfa in improving anemia and eliminating the need for transfusions in multiple myeloma patients refractory to conventional first- or second-line chemotherapy. Forty patients were treated with subcutaneous epoetin alfa (150 IU/kg per dose, increasing to 300 IU/kg per dose, every 3 weeks) for 6 months, and 31 entered a control group. The epoetin alfa group had a significantly (P < or = 0.001) greater percentage of patients (75% vs. 21%) with increases in hemoglobin levels and/or reduced transfusion requirements. In 44 non pre-transfused patients (20 controls, 24 in the epoetin alfa group), the mean increase in hemoglobin was significantly (P < or = 0.0001) greater in the epoetin alfa group (+2.1 vs. -0.2 g/dl). Increases in hematocrit and red blood cells were also significantly (P < or = 0.0001) greater in epoetin alfa-treated patients, with corresponding reductions in transfusion requirement. In the 27 pre-transfused patients (11 controls, 16 in the epoetin alfa group), there was a trend towards reduced transfusional need in epoetin alfa-treated patients. Thus, in patients with multiple myeloma refractory to chemotherapy epoetin alfa is a well-tolerated treatment which improves anemia in non pre-transfused patients and appears to reduce transfusion need in those previously transfused.

Topics: Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Humans; Karnofsky Performance Status; Male; Middle Aged; Multiple Myeloma; Recombinant Proteins

Several studies have suggested that if recombinant human erythropoietin (epoetin) is administered subcutaneously rather than intravenously, a lower dose may be sufficient to maintain the hematocrit at a given level.. In a randomized, unblinded trial conducted at 24 hemodialysis units at Veterans Affairs medical centers, we assigned 208 patients who were receiving long-term hemodialysis and epoetin therapy to treatment with either subcutaneous or intravenous epoetin. The dose was initially reduced until the hematocrit was below 30 percent and then was gradually increased to a level that would maintain the hematocrit in the range of 30 to 33 percent for 26 weeks. We compared the average doses in the 26-week maintenance phase and the discomfort associated with the two routes of administration.. For the 107 patients treated by the subcutaneous route, the average weekly dose of epoetin during the maintenance phase was 32 percent less than that for the 101 patients treated by the intravenous route (mean [+/-SD], 95.1+/-75.0 vs. 140.3+/-88.5 U per kilogram of body weight per week; P<0.001). Only one patient in the subcutaneous-therapy group withdrew from the study because of pain at the injection site, and 86 percent rated the pain associated with subcutaneous administration as ranging from absent to mild.. In patients receiving hemodialysis, subcutaneous administration of epoetin can maintain the hematocrit in a desired target range, with an average weekly dose of epoetin that is lower than with intravenous administration.

Topics: Algorithms; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Humans; Infusions, Intravenous; Injections, Subcutaneous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Pain; Recombinant Proteins; Renal Dialysis

In patients with end-stage renal disease, anemia develops as a result of erythropoietin deficiency, and recombinant human erythropoietin (epoetin) is prescribed to correct the anemia partially. We examined the risks and benefits of normalizing the hematocrit in patients with cardiac disease who were undergoing hemodialysis.. We studied 1233 patients with clinical evidence of congestive heart failure or ischemic heart disease who were undergoing hemodialysis: 618 patients were assigned to receive increasing doses of epoetin to achieve and maintain a hematocrit of 42 percent, and 615 were assigned to receive doses of epoetin sufficient to maintain a hematocrit of 30 percent throughout the study. The median duration of treatment was 14 months. The primary end point was the length of time to death or a first nonfatal myocardial infarction.. After 29 months, there were 183 deaths and 19 first nonfatal myocardial infarctions among the patients in the normal-hematocrit group and 150 deaths and 14 nonfatal myocardial infarctions among those in the low-hematocrit group (risk ratio for the normal-hematocrit group as compared with the low-hematocrit group, 1.3; 95 percent confidence interval, 0.9 to 1.9). Although the difference in event-free survival between the two groups did not reach the prespecified statistical stopping boundary, the study was halted. The causes of death in the two groups were similar. The mortality rates decreased with increasing hematocrit values in both groups. The patients in the normal-hematocrit group had a decline in the adequacy of dialysis and received intravenous iron dextran more often than those in the low-hematocrit group.. In patients with clinically evident congestive heart failure or ischemic heart disease who are receiving hemodialysis, administration of epoetin to raise their hematocrit to 42 percent is not recommended.

Topics: Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Prospective Studies; Recombinant Proteins; Renal Dialysis

The cost of managing anemia with prophylactic epoetin alfa therapy versus blood transfusions in breast cancer patients receiving combination chemotherapy was studied. A retrospective study of anemia in breast cancer patients treated with four cycles of cyclophosphamide and doxorubicin with fluorouracil (CAF) or without fluorouracil (CA) was conducted. For each cycle of chemotherapy, patients were assessed for fatigue, subsequent blood transfusions administered, and potential response to and adverse effects of blood transfusions. Transfusions were given at the prescriber's discretion rather than in accordance with standard guidelines. The lowest hemoglobin concentration and hematocrit of each patient per cycle were reported. Data on these patients, along with data from published studies of prophylactic use of epoetin alfa, were used in a decision analysis of the costs associated with using epoetin alfa versus red blood cell transfusions to manage anemia. The charts of 50 patients were reviewed. In the study group, the percentage of patients with anemia and the frequency of fatigue rose with each chemotherapy cycle. In general, blood transfusions were not used. The cost of using epoetin alfa prophylactically for all four cycles was estimated at $6483 per patient for the literature-based group versus $169 for the study group. The cost of managing anemia in breast cancer patients was substantially lower when blood transfusions were used than when epoetin alfa was given prophylactically throughout four cycles of therapy with CAF or CA; the absence of standard guidelines for transfusion might have exaggerated the difference in costs.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Decision Trees; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Fatigue; Female; Hematinics; Humans; MEDLINE; Recombinant Proteins; Retrospective Studies

Anemia, one of the most common complications of cancer chemotherapy, has been managed with red blood cell (RBC) transfusions. As an alternative, the agent epoetin alfa has the potential to reduce the transfusion requirements of patients receiving cancer chemotherapy. To estimate the value that cancer patients place on the drug, an economic analysis using the concept of willingness to pay (WTP) was conducted.. The method of WTP was used within the framework of a classical cost-benefit analysis to estimate the net cost or benefit of administering prophylactic epoetin alfa to cancer patients. This estimate included the direct cost of epoetin alfa administration and savings secondary to reduced RBC transfusions. A cohort of 100 cancer patients who received or were scheduled to receive cisplatin or noncisplatin chemotherapy (50 per group) were then interviewed to measure the maximum WTP (net benefit) that they experienced with epoetin alfa.. Regarding the benefits they would experience after 3 months of epoetin alfa administration, patients receiving cisplatin and noncisplatin therapy stated that they would be willing to pay an average of 587 U.S. dollars (U.S.$587) (95%CI: $300-$875) and U.S.$613 (95%CI: $324-$902), respectively. These benefits were then subtracted from the total cost of the drug when administered to patients receiving cisplatin (U.S.$3530) and noncisplatin (U.S.$3653) therapy. This produced a net incremental treatment cost of U.S.$2943 (95%CI: $2655-$3230) and U.S.$3039 (95%CI: $2750-$3328) for the respective treatment groups.. The results of the current study suggest that the routine administration of epoetin alfa to cancer patients receiving myelosuppressive chemotherapy is a highly resource-intensive treatment policy with modest benefit to patients. Additional research is required to identify high risk patient subgroups who would benefit most from the drug. [See editorial on pages 2427-9, this issue.]

Topics: Anemia; Antineoplastic Agents; Cisplatin; Cost-Benefit Analysis; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Health Services Needs and Demand; Hematinics; Humans; Income; Life Expectancy; Male; Middle Aged; Multivariate Analysis; Neoplasms; Prescription Fees; Recombinant Proteins; Sensitivity and Specificity; Socioeconomic Factors

Untreated anemia is common in cancer patients. Previous studies have demonstrated that both the existence of cancer and treatment with chemotherapy can suppress the normal endogenous erythropoietic response to anemia, making some cancer patients transfusion cadidates. In placebo-controlled phase III studies, administration of recombinant human erythropoietin (epoetin alfa) increased hemoglobin (Hb) levels and decreased transfusion requirements in patients undergoing cancer chemotherapy. In these studies, an increase in self-perceived energy level, functional status, and overall quality of life (QOL) was noted in the subset of patients in whom hematocrit levels increased by > or = 6%. To examine more closely the relationship between epoetin alfa therapy and QOL issues in patients undergoing chemotherapy, we conducted an open-label phase IV study involving 2,030 patients treated at 570 community cancer centers in the United States. Patients initially received epoetin alfa 150 U/kg subcutaneously (s.c.) three times per week for 4 months; if response was judged inadequate, the dosage was increased after 8 weeks to 300 U/kg s.c. three times per week. Hb levels and transfusion requirements were monitored monthly. Before and after the study, each patient completed a linear analog self-assessment scale designed to measure energy level, daily activity, and overall QOL. During epoetin alfa therapy, there was a progressive and significant increase (P < .001) in Hb concentrations. Significantly fewer (P < .001) patients were transfused and fewer transfusions were administered per patient per month after the first month of epoetin alfa therapy. Fifty-eight percent of the patients who required a transfusion during the first month of epoetin alfa therapy did not require a transfusion during the subsequent 3 months of the study. The entire patient population demonstrated a significant increase in mean scores for energy level, daily activity, and overall QOL. The magnitude of the increase in these scores correlated with the magnitude of the increase in Hb concentration. Statistically significant improvement in energy scores, daily activity, and overall QOL (P < .05) were observed, regardless of tumor response. These observations require confirmation on placebo-controlled trials, but the implications for oncology practice are important. They suggest that in cancer patients undergoing chemotherapy, the tradition of leaving anemia untreated may compromise patients' ability t

Topics: Administration, Cutaneous; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Neoplasms; Quality of Life; Recombinant Proteins

Two previous short-term studies (12 weeks and up to 16 weeks) that used androgens to supplement recombinant human erythropoietin (rHuEPO) for the treatment of the anemia associated with end-stage renal disease showed divergent results. Both studies were limited by their brief duration, since the hematopoietic effect of androgens does not peak until 5 months. Therefore, we conducted a 6-month, prospective, randomized trial comparing low-dose rHuEPO alone and in combination with androgens for the treatment of the anemia of end-stage renal failure. Nineteen anemic chronic hemodialysis patients were randomized into two groups. Group A (n = 10) received 1,500 U rHuEPO intravenously three times a week for 26 weeks. Group B (n = 9) received the same dose of rHuEPO plus nandrolone decanoate 100 mg intramuscularly weekly. Baseline transferrin saturation, serum ferritin, intact serum parathyroid hormone, plasma aluminum, and hematocrit levels were not significantly different between the groups. At study completion, both groups showed a significant increase in mean hematocrit compared with baseline (group A: 24.8% +/- 1.4% to 28.3% +/- 2.8%, P = 0.003; group B: 25.1% +/- 1.5% to 33.2% +/- 4.5%, P = 0.001). The increase in hematocrit in the rHuEPO plus androgen-treated group was statistically greater than in the rHuEPO-alone group (8.2% +/- 4.4% v 3.5% +/- 2.8%; P = 0.012). With the exception of mild discomfort at the injection site, there were no significant side effects from nandrolone. We conclude that the combination of low-dose rHuEPO and nandrolone decanoate is effective treatment for the anemia of end-stage renal failure.

Topics: Anabolic Agents; Anemia; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nandrolone; Nandrolone Decanoate; Prospective Studies; Recombinant Proteins; Renal Dialysis; Time Factors

Current evidence suggests that epoetin alpha administration is well tolerated and effective in the management of anemia of cancer and cancer chemotherapy. An open-label, multinational, non-comparative study was conducted in 215 cancer patients with anemia secondary to chemotherapy with platinum- or non-platinum-based combinations. Epoetin alpha was administered s.c. (150 IU/kg three times/week) for a planned period of 16 weeks. The response rate of epoetin alpha, defined as an increase in hemoglobin level of 2 g/dl or more from baseline, was 67%. The rate of response was not related to the chemotherapy regimen administered (platinum or non-platinum based). The percentage of patients transfused and the transfusion rate during epoetin alpha treatment were reduced. Transfusional need was eliminated in 64 (75%) of the 85 patients transfused before the study start, after 1 month of therapy. Quality of life, assessed using a visual analog scale, improved markedly in patients who experienced a hematological response. These patients also experienced a statistically significant (p < 0.0001) improvement in mean WHO performance score. These findings indicate that epoetin alpha is a well tolerated and effective agent which increases hemoglobin concentration and reduces transfusion requirements in anemic cancer patients receiving chemotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Carboplatin; Cisplatin; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins

The ability of epoetin alfa to increase hematopoiesis in a dose-dependent manner when administered by the intravenous (i.v.) or subcutaneous (s.c.) route has been demonstrated in pharmacokinetic studies in healthy volunteers. Epoetin alfa may therefore be a useful adjunct to autologous blood (AB) donation. By facilitating AB donation, the use of allogeneic blood could be reduced. In patients scheduled to undergo orthopedic surgery, i.v. administration of epoetin alfa 600 IU/kg twice weekly for 3 weeks prior to surgery (in conjunction with oral iron supplementation) significantly increased the number of AB units and total red blood cell (RBC) volume donated and increased the number of patients able to donate > or = 4 AB units. However, there was no difference between epoetin alfa and placebo groups with respect to allogeneic blood exposure.

Topics: Anemia; Blood Transfusion, Autologous; Epoetin Alfa; Erythropoiesis; Erythropoietin; Ferrous Compounds; Hematocrit; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Orthopedics; Premedication; Recombinant Proteins

Predonation of autologous blood (AB) represents an attractive alternative to allogeneic blood transfusion in patients scheduled for elective orthopedic surgery. However, anemic patients may not be able to donate sufficient AB prior to surgery, thus increasing the risk of exposure to allogeneic blood. This group of patients may benefit from the administration of epoetin alfa to facilitate AB donation. A recent multicenter, double-blind, placebo-controlled study in 204 patients with a low hematocrit (Hct; < or = 39%) scheduled for orthopedic surgery demonstrated that the intravenous administration of epoetin alfa (600 IU/kg twice weekly for 3 weeks) significantly increased the number of AB units predeposited and the percentage of patients able to donate > or = 4 AB units. Furthermore, epoetin alfa attenuated the decrease in Hct associated with AB donation and significantly (P = .027) reduced allogeneic blood exposure in these patients.

Topics: Anemia; Blood Transfusion; Blood Transfusion, Autologous; Double-Blind Method; Elective Surgical Procedures; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferrous Compounds; Hematocrit; Humans; Male; Orthopedics; Premedication; Recombinant Proteins; Treatment Outcome

In patients scheduled for major orthopedic surgery, the presence of anemia can preclude the donation of sufficient autologous blood (AB) to meet transfusion requirements. Although a number of studies have investigated the use of epoetin alfa (in conjunction with parenteral iron supplementation) to facilitate AB donation and reduce exposure to allogeneic blood in this patient population, the optimum treatment regimen and route of administration has yet to be defined. In rheumatoid arthritis (RA) patients with a low predonation hematocrit (Hct; < or = 39%), intravenous (i.v.) treatment with epoetin alfa 300 IU/kg twice weekly for 3 weeks was the optimum dosage for facilitation of AB donation and minimization of the decrease in Hct prior to elective orthopedic surgery. However, the subcutaneous (s.c.) route of epoetin alfa administration may allow lower dosages of epoetin alfa to be used. Indeed, epoetin alfa 100 IU/kg s.c. twice weekly for 3 weeks (in conjunction with a single i.v. bolus of 200 IU/ kg at the first s.c. dose) was as effective as 300 IU/kg i.v. administered according to the same schedule. The number of AB units collected, total red blood cell (RBC) volume donated, and peak proportion of reticulocytes were similar regardless of the route of administration. Both treatment groups were associated with a significant reduction in allogeneic blood exposure compared with historical controls. Findings consistent to all of these studies were that epoetin alfa was well tolerated, and that i.v. iron supplementation was necessary to maximize its beneficial effects.

Topics: Anemia; Arthritis, Rheumatoid; Blood Transfusion; Blood Transfusion, Autologous; Dose-Response Relationship, Drug; Double-Blind Method; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematocrit; Humans; Injections, Intravenous; Injections, Subcutaneous; Orthopedics; Premedication; Recombinant Proteins; Treatment Outcome

A low predonation hematocrit (Hct) can preclude the collection of sufficient autologous blood (AB) to meet the transfusion requirements of patients scheduled for orthopedic surgery. Subcutaneous (s.c.) administration of epoetin alfa, in conjunction with intravenous (i.v.) iron supplementation, has proved effective for the facilitation of AB donation by such patients. Compared with untreated controls and patients treated with i.v. iron alone, epoetin alfa 50 to 150 IU/kg SC plus i.v. iron twice weekly for 3 weeks prior to surgery significantly increased total red blood cell (RBC) production (P < .01) and the volume of RBCs donated (P < .05). Epoetin alfa was particularly effective in females and patients with a predicted blood volume (PBV) less than 5 L. Treatment with epoetin alfa led to an increase (albeit nonsignificant) in the number of AB units predonated compared with i.v. iron alone. However, in patients with a PBV less than 5 L, a substantially greater percentage of epoetin alfa-treated patients donated > or = 4 AB units (80% v 30%). Allogeneic blood requirements were reduced, albeit not significantly (P = .051), in patients treated with epoetin alfa. However, in comparison with untreated controls, there was a significant reduction in the mean volume of allogeneic blood transfused per transfused patient in the epoetin alfa groups. The optimum s.c. dose of epoetin alfa in patients with a low predonation Hct scheduled for orthopedic surgery appears to be between 100 and 150 IU/kg twice weekly for 3 weeks.

Topics: Anemia; Blood Transfusion; Blood Transfusion, Autologous; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematocrit; Humans; Male; Orthopedics; Premedication; Recombinant Proteins; Reticulocyte Count; Sex Characteristics; Treatment Outcome

The development of anemia is one factor that can limit the donation of sufficient autologous blood (AB) to meet a patient's expected blood requirements following elective orthopedic surgery. Two clinical studies have been conducted in nonanemic patients to investigate the use of epoetin alfa as an adjuvant to AB predonation to facilitate AB procurement and minimize the development of anemia. Both studies demonstrated that patients with a normal hematocrit (Hct) can donate > or = 3 units of AB prior to surgery. However, treatment with epoetin alfa minimized the decrease in Hct associated with AB donation. While there was a trend toward a reduction in allogeneic blood exposure in patients treated with epoetin alfa, the difference relative to placebo was not significant. This observation may be explained by a limited requirement for blood in this patient population that was met by predonation of 3 AB units. Thus, the use of epoetin alfa as an adjunct to AB predonation is likely to be of most benefit in patients with a normal Hct scheduled for surgical procedures where the expected blood requirements exceed 3 units. In addition, epoetin alfa may enable patients with a low Hct, low body weight, or low predicted blood volume to participate in or to complete an AB donation program, thus reducing the possibility of exposure to allogeneic blood.

Topics: Anemia; Blood Transfusion; Blood Transfusion, Autologous; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematocrit; Hemoglobins; Humans; Iron; Orthopedics; Premedication; Recombinant Proteins; Treatment Outcome

Patients undergoing cancer surgery frequently require blood, and the transfusion of allogeneic blood in these patients has been controversially linked to an increased risk of tumor recurrence. This patient population may therefore benefit from preoperative autologous blood donation (ABD) with or without epoetin alfa therapy, although the precise impact of autologous blood transfusion has not been fully explored. In some trials, preoperative ABD reduced allogeneic blood exposure by 50% in patients undergoing surgery for cancer resection, while, in another study, perioperative treatment with epoetin alfa significantly increased hematocrit (Hct) levels preoperatively and led to a reduction in postoperative allogeneic blood exposure. A combination of epoetin alfa and preoperative ABD seems a reasonable approach to reducing allogeneic blood exposure in patients undergoing cancer surgery.

Topics: Anemia; Blood Transfusion; Blood Transfusion, Autologous; Colorectal Neoplasms; Disease-Free Survival; Epoetin Alfa; Erythropoiesis; Erythropoietin; Gastrointestinal Neoplasms; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Premedication; Prospective Studies; Recombinant Proteins; Survival Rate; Transfusion Reaction; Treatment Outcome

Several strategies have been investigated as a means of reducing allogeneic blood requirements in patients undergoing surgery, including the perioperative administration of epoetin alfa. In a multicenter, double-blind, placebo-controlled study in 208 patients undergoing elective hip replacement surgery, subcutaneous administration of epoetin alfa (300 IU/kg daily) for 14 or 9 days perioperatively (commencing 10 and 5 days preoperatively, respectively) significantly reduced the incidence of primary outcome events (any allogeneic blood transfusion or a postoperative hemoglobin [Hb] level < 8.0 g/dL) compared with placebo (P = .003). Furthermore, the transfusion requirements of epoetin alfa-treated patients were significantly lower than those of patients treated with placebo (P = .007). Preoperative and postoperative Hb levels and reticulocyte counts were higher in epoetin alfa-treated patients compared with placebo. Epoetin alfa was well tolerated, and the incidence of deep vein thrombosis (DVT) was not different from that observed in placebo recipients. Thus, perioperative administration of epoetin alfa reduces the allogeneic blood requirements of patients undergoing elective hip replacement surgery and is of particular benefit in the subgroup of patients whose baseline Hb levels are less than 13.5 g/dL.

Topics: Anemia; Blood Transfusion; Dose-Response Relationship, Drug; Double-Blind Method; Elective Surgical Procedures; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hemoglobins; Hip Prosthesis; Humans; Injections, Subcutaneous; Premedication; Recombinant Proteins; Reticulocyte Count; Treatment Outcome

In order to avoid exposure to allogeneic blood, perisurgical administration of epoetin alfa has been proposed as an alternative to autologous blood (AB) predonation in patients who are unable or unwilling to donate AB prior to elective surgery. The efficacy of perisurgical epoetin alfa to reduce allogeneic blood exposure was investigated in a randomized, double-blind, placebo-controlled study in 200 patients unable to participate in an AB predonation program who were scheduled for orthopedic surgery with expected blood loss > or = 2 units. Epoetin alfa (100 IU/kg or 300 IU/kg) was administered daily by subcutaneous (s.c.) injection, commencing 10 days preoperatively and continuing until day 4 postoperatively (15 doses in total). All patients received oral iron supplementation. Patients treated with epoetin alfa required significantly fewer (P < .001) allogeneic transfusion compared with placebo, and this effect of epoetin alfa was particularly evident in the subgroup of patients with baseline hemoglobin (Hb) levels of more than 10 to < or = 13 g/dL. In terms of the reduction in allogeneic blood exposure, no significant difference was evident between epoetin alfa regimens. Epoetin alfa was well tolerated. Although 15 s.c. doses of epoetin alfa 100 IU/kg appears to be the optimum dosage regimen in patients scheduled for orthopedic surgery, a presurgical simulation study in 24 healthy volunteers suggested that two s.c. doses of epoetin alfa 600 IU/kg in 10 days prior to expected surgery may be a suitable regimen for further study. However, the optimum timing of epoetin alfa administration in relation to surgery remains to be established. A finding consistent to all studies is that adequate iron supplementation (most probably in parenteral form) is necessary to optimize the erythropoietic response to epoetin alfa in the surgical setting.

Topics: Anemia; Blood Transfusion; Dose-Response Relationship, Drug; Double-Blind Method; Elective Surgical Procedures; Epoetin Alfa; Erythropoiesis; Erythropoietin; Ferrous Compounds; Humans; Injections, Subcutaneous; Orthopedics; Premedication; Recombinant Proteins; Transferrin; Treatment Outcome

We sought to determine the rate and extent of iron utilization after administration of intravenous iron dextran and to compare the efficacy of iron dextran preparations of differing molecular weight. We randomized patients to receive either a 500-mg dose of iron dextran molecular weight (MW) 267,000 (group A) or iron dextran MW 96,000 (group B) administered in five sequential 100-mg doses, and examined indices of iron status before and at weekly intervals up to 4 weeks later. Although mean iron utilization was greater in the nine group A patients (46.7% +/- 21.3%) than in the 11 group B patients (31.7% +/- 26.6%), the difference was not statistically significant (P = 0.19). Iron utilization in both groups was substantially incomplete. Changes in serum ferritin and hemoglobin did not differ between the treatments (P = 0.49 and P = 0.34, respectively). We conclude that iron utilization after iron dextran administration is substantial within the first week after completing a course of therapy, associated with stable iron indices after the first 2 weeks, and incomplete for at least the first 4 weeks. Degree of iron utilization appears independent of molecular weight within the range we examined.

Topics: Anemia; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Injections, Intravenous; Iron; Iron Deficiencies; Iron-Dextran Complex; Male; Middle Aged; Molecular Weight; Prospective Studies; Recombinant Proteins; Renal Dialysis; Transferrin

Neonates with Rhesus hemolytic disease can present with anemia beyond 1 wk of age due to bone marrow suppression and low erythropoietin secretion. Erythropoietin stimulating agents (ESA) were tried to manage anemia in these neonates. Darbepoetin alfa (DA) is a long-acting ESA used to treat anemia in premature neonates and in children with chronic kidney disease or on cancer chemotherapy. The authors present their experience of using DA to treat late-onset hyporegenerative anemia in 3 neonates with Rhesus isoimmunization. Darbepoetin alfa 4 mcg/kg was given subcutaneously at a 1-2-wk interval to target hemoglobin of 10-12 g/dL. No adverse effects were observed, and the treated infants had a reduced need for the packed red blood cell transfusions.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythroblastosis, Fetal; Erythropoietin; Female; Hematinics; Hemoglobins; Humans

This study was undertaken to evaluate the long-term clinical efficacy of epoetin alfa and darbepoetin alfa in patients with myelodysplastic syndrome (MDS) in a real-life setting.. A total of 204 patients with low-risk or intermediate-1-risk MDS who received epoetin alfa or darbepoetin alfa were included. Hemoglobin levels and transfusion needs were recorded before treatment and at 12 months, 24 months, 36 months, and 48 months of treatment.. At the 36-month (p=0.025) and 48-month (p=0.022) visits, epoetin alfa yielded significantly higher hemoglobin levels compared to darbepoetin alfa. Transfusion needs were also significantly lower with epoetin alfa compared to darbepoetin alfa at 24 months (p=0.012) and in the low-risk group compared to the intermediate-risk group at 24 months (p=0.018), 36 months (p=0.025), and 48 months (p<0.001). Treatment response rates at the 24-month, 36-month, and 48-month visits in the epoetin alfa (43.0%, 33.6%, and 27.1%), darbepoetin alfa (29.9%, 22.7%, and 16.5%), low-risk (39.3%, 30.0%, and 26.0%), and intermediate-risk (29.6%, 24.1%, and 11.1%) groups were lower than those obtained at 12 months, and the values differed significantly for the 36-month and 48-month visits with values ranging from p<0.05 to p<0.001.. This real-life long-term ESA extension study investigated the clinical efficacy of epoetin alfa and darbepoetin alfa for up to 48 months, revealing that treatment efficacy reached a plateau starting from the 24. Myelodisplastik sendromlu (MDS) hastalarda epoetin alfa ve darbepoetin alfa tedavisinin gerçek yaşam ortamında uzun-dönem klinik etkinliğini değerlendirmek.. Bu çalışmaya düşük veya orta-1 risk grubu MDS tanısı ile epoetin alfa veya darbepoetin alfa tedavisi almış 204 hasta dahil edildi. Hemoglobin düzeyleri ve transfüzyon gereksinimi, tedaviden önce ve tedavinin 12., 24., 36. ve 48. aylarında değerlendirildi.. Epoetin alfa, darbepoetin alfa ile kıyaslandığında, 36. ay (p=0,025) ve 48. aylarda (p=0,022) anlamlı şekilde daha yüksek hemoglobin düzeylerini sağladı. Transfüzyon gereksinimi 24. ayda (p=0,012) epoetin alfa grubunda darbepoetin alfa grubuna göre, 24. ay (p=0,018), 36. ay (p=0,025) ve 48. aylarda (p<0,001) ise düşük risk grubunda orta risk grubuna göre anlamlı şekilde daha düşük olarak bulundu. Tedavi yanıt oranları 24. ay, 36. ay ve 48. aylarda epoetin alfa (%43,0, %33,6 ve %27,1), darbepoetin alfa (%29,9, %22,7 ve %16,5), düşük risk (%39,3, %30,0 ve %26,0) ve orta risk (%29,6, %24,1 ve %11,1) gruplarında 12. ay yanıt oranlarına göre daha düşük olup, 36. ve 48. aylarda bu değişim istatistiksel olarak anlamlı idi (p<0,05 ile <0,001 arası).. Epoetin alfa ve darbepoetin alfanın 48 aylık klinik etkililiğinin değerlendirildiği bu gerçek-yaşam uzun-dönem ESA çalışmasında, tedavi etkililiğinin tedavinin 24. ayından başlayarak plato evresine eriştiği ve devamında tedavi yanıt oranlarında, tedavi tipi, risk durumu veya cinsiyetten bağımsız olarak süregiden bir düşüşün gerçekleştiği saptandı. Bununla birlikte, epoetin tedavisi alan grupta darbepoetin ile tedavi edilen gruba göre ve düşük risk grubu hastalarda orta risk grubu hastalara göre, hemoglobin düzeyleri anlamlı şekilde daha yüksek olup, transfüzyon gereksiniminde de belirgin azalma olduğu tespit edildi.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Hemoglobins; Humans; Myelodysplastic Syndromes; Recombinant Proteins

Epoetin has been used to treat patients with renal anemia since 1988. -Anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA) has been associated with epoetin usage, and a PRCA incidence of 4.5 per 10,000 patient-years was observed for epoetin-α (Eprex) in 2002. The PASCO II study (post-authorization safety cohort observation of Retacrit and Silapo (epoetin-ζ) administered subcutaneously for the treatment of renal anemia) followed 6,346 patients (4,501 Retacrit (group R); 1,845 Silapo (group S)) for up to 3 years of subcutaneous treatment with the biosimilar epoetin-ζ. One PRCA in 1 (0.02%) patient in group R who tested positive for neutralizing antibodies was reported. Overall, 527 adverse events of special interest (AESI) including PRCA occurred in 418 (6.60%) patients, lack of efficacy occurred in 34 (0.54%), and thromboembolic events in 389 (6.14%) patients. 41 adverse drug reactions other than AESIs were reported in 28 (0.44%) patients. The exposure-adjusted incident rate of PRCA was 0.84 per 10,000 patient-years. This real-world study showed that among patients with renal anemia receiving subcutaneous administration of the biosimilar product epoetin-ζ, the incidence rate of PRCA was substantially below the risk observed in 2002 for Eprex and that there was no immunogenicity concern or other new safety concern.

Topics: Anemia; Biosimilar Pharmaceuticals; Chronic Disease; Epoetin Alfa; Hematinics; Humans; Kidney Diseases; Recombinant Proteins; Red-Cell Aplasia, Pure

Anemia in patients with chronic kidney disease (p-CKDs) may initiate or exacerbate left ventricular hypertrophy (LVH). This study aimed to determine whether treatment using long-acting erythropoietin-stimulating agents (L-ESAs) is independently associated with LVH during the pre-dialysis to maintenance dialysis period in p-CKDs.. Physical and laboratory examinations were performed 120 days before initiating dialysis in p-CKDs (baseline). To evaluate the left ventricular mass index (LVMI) after starting dialysis, the mean hemoglobin (Hb) was defined as the average at the start of dialysis and 6 months after starting dialysis. Changes in the LVMI were observed in three groups according to mean Hb levels (Hb < 10.1, 10.1 < Hb < 11.0, and Hb > 11.0 g/dL for Groups 1, 2, and 3, respectively). LVMI was evaluated using echocardiography at the pre-dialysis, initiation, and maintenance dialysis periods.. A lower LVMI at dialysis initiation and an improvement in LVMI were detected in the highest tertile group of mean Hb (11.0 g/dl). Consequently, in the high Hb group (Hb level > 11.0 g/dl), LVMI remained low from dialysis initiation until after 6 months.The relationship between Hb and LVMI was not significant; however, a constant correlation with β ≥ 0.4 in the absolute value was maintained.. L-ESAs may correlate with Hb and LVMI after administration, independent of the baseline LVMI and Hb values. These findings have therapeutic implications in the treatment strategies for p-CKDs during the pre-dialysis to maintenance dialysis period.

Topics: Anemia; Dialysis; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Longitudinal Studies; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies

This study was conducted to evaluate whether the efficacy and safety profile of recombinant human erythropoietin (rhEPO) manufactured by Daewoong Pharmaceutical Co., Ltd was similar to biological products approved by the drug safety regulatory authority.. It was an open-label, randomized, comparative, parallel, multi-center study in hemodialysis patients with anemia. The reference product at an individualized dose 3 times a week was given in 4-8 weeks of titration period and hemoglobin (Hb) level was controlled to reach the range of 10-12 g/dL. Then, the subjects were randomly administered with reference or test product with the same dose regimen. The primary endpoints were to demonstrate the Hb level change between baseline and evaluation period in both treatment groups, while the secondary endpoints were the mean change in weekly dosage per kg body weight and the instability rate of Hb level during maintenance and evaluation period. The safety was evaluated based on the adverse events incidence.. There was no statistical difference in the change of Hb between test and reference (0.14 g/dL and 0.75 g/dL respectively, with p>0.05), also for the mean changes of weekly dosage between groups (1091.40 IU and 570.15 IU respectively, with p>0.05). The instability rate of Hb in both test and reference was not statistically significantly different as well (26 and 15% respectively, with p>0.05).. This study proves that the efficacy indicated by the change instability of Hb and safety indicated by adverse event incidence of Epodion and the reference product on chronic kidney disease were similar.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Insufficiency, Chronic; Treatment Outcome

This cohort study was designed to explore whether roxadustat or erythropoietin could affect thyroid function in patients with renal anemia.. The study involved 110 patients with renal anemia. Thyroid profile and baseline investigations were carried out for each patient. The patients were divided into two groups: 60 patients taking erythropoietin served as the control group (rHuEPO group) and 50 patients using roxadustat served as the experimental group (roxadustat group).. The results indicated that there were no significant differences in serum total thyroxine (TT4), total triiodothyronine (TT3), free triiodothyronine (FT3), free thyroxine (FT4) or thyroid stimulating hormone (TSH) between the two groups at baseline. After treatment, TSH, FT3, and FT4 were significantly lower in the roxadustat group than in the rHuEPO group (. Roxadustat may lead to a higher risk of thyroid dysfunction, including low TSH, FT3 and FT4, than rHuEPO in patients with renal anemia.

Topics: Anemia; Chronic Disease; Cohort Studies; Epoetin Alfa; Erythropoietin; Humans; Kidney Diseases; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Pure red cell aplasia (PRCA) associated with erythropoiesis-stimulating agents (ESAs), which were first reported in 1998, usually occurs with subcutaneous administration of epoetin alfa (Eprex

Topics: Anemia; Antibodies; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Polyethylene Glycols; Prednisolone; Recombinant Proteins; Red-Cell Aplasia, Pure

The aim of the study was to evaluate in real-life conditions the effectiveness and safety of a biosimilar of epoetin alfa (Retacrit®) in chemotherapy-induced anemia and the impact of iron supplementation.. This was a longitudinal, observational, prospective study of 12-16 weeks conducted in 195 French centers. The primary endpoint was the achievement of target Hb (with an increase of Hb ≥1 g/dL) or an increase of Hb ≥2 g/dL, in the absence of transfusion in the previous 3 weeks.. 2,076 patients (women, 50.6%; mean age, 67.0 years) with malignant diseases (solid tumors, 79.8%; lymphomas, 12.7%; multiple myeloma, 6.6%) were analyzed. A total of 655 patients received oral iron (40.5%), intravenous iron (58.9%), or both (0.6%). At inclusion, 10.0% and 18.2% of patients without and with iron supplementation had serum ferritin <100 μg/L, respectively. Transferrin saturation (TSAT) ≤20% was more frequent in patients with supplementation (76.6%) than without supplementation (33.9%). The mean weekly doses of epoetin alfa biosimilar and planned duration of treatment were comparable regardless of iron supplementation. The primary endpoint was achieved in 70.5% and 70.2% of patients without and with iron supplementation, respectively. Three (0.1%) serious thromboembolic events related to treatment with epoetin alfa biosimilar were reported.. Epoetin alfa biosimilar was effective and well tolerated for treating chemotherapy-induced anemia. Patients in subgroup with iron supplementation had lower TSAT at inclusion compared to subgroup without supplementation. Comparable mean Hb levels were achieved in both subgroups. The rate of patients with iron supplementation through the intravenous route was however insufficient.

Topics: Aged; Anemia; Antineoplastic Agents; Biosimilar Pharmaceuticals; Dietary Supplements; Epoetin Alfa; Female; Ferritins; Hematinics; Humans; Iron; Neoplasms; Prospective Studies; Recombinant Proteins; Transferrins

In 2011, the Centers for Medicare & Medicaid Services implemented bundling of all services for patients receiving dialysis, including erythropoietin-stimulating agents use, and the Food and Drug Administration recommended conservative erythropoietin-stimulating agent dosing.. This retrospective cohort study investigated anemia care and clinical outcomes before and after the Centers for Medicare & Medicaid Services bundled payment and the revised Food and Drug Administration-recommended erythropoietin-stimulating agent labeling for Medicare-insured adults receiving hemodialysis using data from the United States Renal Data System from January 1, 2006 to December 31, 2016. Clinical outcomes included major adverse cardiovascular event (stroke, acute myocardial infarction, and all-cause mortality), cardiovascular mortality, and heart failure. Measurements were compared between prepolicy (2006-2010) and postpolicy (2012-2016) implementation using interrupted time series and Cox proportional hazards regression models.. The Medicare reimbursement policy and Food and Drug Administration-recommended erythropoietin-stimulating agent dosing changes were associated with lower erythropoietin-stimulating agent use and lower hemoglobin levels. These changes in anemia care were associated with lower risks of major adverse cardiovascular event, stroke, mortality, and heart failure but higher risk of acute myocardial infarction among adults receiving hemodialysis.

Topics: Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Heart Failure; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Medicare; Myocardial Infarction; Policy; Renal Dialysis; Retrospective Studies; Stroke; United States

Anemia due to chronic kidney disease (CKD) is often associated with decreased erythropoietin (EPO) levels in the blood. Treatments available are improving blood iron levels and administration of exogenous EPO (rhEPO). This study aims to assess the safety and immunogenicity of Epodion, a biosimilar rhEPO product, in haemodialysis patients with CKD-associated anaemia in three Indonesian hospitals.. This prospective, open label, single arm, and multicenter study enrolled patients with anemia associated with CKD under hemodialysis treatment. Patient eligibility was assessed within the 4-week screening period. Blood samples for determination of erythropoietin antibody (Anti-Drug Antibody) were taken at week-0, 24, and 52 using a validated and highly sensitive bridging ELISA method. Evaluation of Neutralizing Antibody (NAb) was carried out to confirm the impact of the antibody to pharmacological activity (e.g., antibody-mediated PRCA) when the ADA detection of patients was positive after screening and confirmatory assay.. Results from all tested patients show that Epodion could maintain hemoglobin and hematocrit levels. ADA detection using ELISA assay yielded negative results for all plasma samples of week-24 and week-52, so the evaluation of NAb was not carried out. No adverse events were considered relevant to tested product.. This study proves no immunogenic effect of Epodion on stimulating immune system's antibodies in Indonesian patients with CKD-associated anemia.

Topics: Anemia; Antibodies, Neutralizing; Biosimilar Pharmaceuticals; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Iron; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic

Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, increases hemoglobin by stimulating erythropoietin synthesis and improving iron availability through facilitation of iron uptake and/or release from stores. In this exploratory analysis, we assessed the effect of roxadustat treatment on laboratory parameters related to iron metabolism in patients with anemia of chronic kidney disease (CKD).. Data were pooled from pivotal, randomized, phase 3 roxadustat trials: three placebo-controlled, double-blind trials in nondialysis-dependent (NDD) CKD and three open-label, active-comparator (epoetin alfa) trials in dialysis-dependent (DD) CKD. In this exploratory analysis, mean changes from baseline in hemoglobin, iron parameters, and hepcidin, and intravenous (iv) iron use were evaluated. Pooled results in NDD CKD and DD CKD patients are reported.. Overall, 4277 patients with NDD CKD and 3890 patients with DD CKD were evaluated. Hemoglobin increases with roxadustat treatment were accompanied by increases in serum iron and total iron-binding capacity (TIBC) and decreases in serum ferritin and hepcidin from baseline through week 52. With epoetin alfa, the hemoglobin increase was accompanied by decreases in serum ferritin and hepcidin, but serum iron decreased, and there was no change in TIBC. With placebo, there were no changes in hemoglobin, iron parameters, or hepcidin. During treatment, iv iron use was reduced with roxadustat versus placebo and epoetin alfa.. In patients with NDD CKD and DD CKD, roxadustat treatment is associated with increases in serum iron and TIBC, accompanied by reduced hepcidin and indicative of improved iron kinetics. Patients treated with roxadustat achieved target hemoglobin levels with less iv iron use versus comparators. Practitioners treating patients with anemia of CKD with roxadustat should consider its unique effects when interpreting iron parameters.

Topics: Anemia; Clinical Trials, Phase III as Topic; Epoetin Alfa; Erythropoietin; Ferritins; Glycine; Hemoglobins; Hepcidins; Humans; Iron; Isoquinolines; Prolyl-Hydroxylase Inhibitors; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic

Erythropoiesis-stimulating agents (ESAs) are effective drugs to correct and maintain haemoglobin (Hb) levels, however, their use at doses to reach high Hb targets has been associated with an increased risk of cardiovascular adverse events, mortality and cancer. Presently used ESAs have a common mechanism of action but different pharmacokinetic and pharmacodynamic characteristics. Accordingly, the mode of activation of the erythropoietin (EPO) receptor can exert marked differences in downstream events. It is unknown whether the various ESA molecules have different efficacy/safety profiles. The relative mortality and morbidity risks associated with the use of different types of ESAs remains poorly evaluated. Recently an observational study and a randomized clinical trial provided conflicting results regarding this matter. However, these two studies displayed several differences in patient characteristics and ESA molecules used. More importantly, by definition, randomized clinical trials avoid bias by indication and suffer less from confounding factors. Therefore they bring a higher degree of evidence. The scenario becomes even more complex when considering the new class of ESAs, called prolyl-hydroxylase domain (PHD) inhibitors. They are oral drugs that mimic exposure to hypoxia and stabilize hypoxia-inducible factor α. They profoundly differ from presently used ESAs, as they have multiple targets of action, including the stimulation of endogenous EPO synthesis, direct mobilization/absorption of iron and a higher reduction of hepcidin. Accordingly, they have the potential to be more effective in inflamed patients with functional iron deficiency, i.e. the setting of patients who are at higher risk of cardiovascular events and mortality in response to present ESA use. As for ESAs, individual PHD inhibitors differ in molecular structure and degree of selectivity for the three main PHD isoforms; their efficacy and safety profiles may therefore be different from that of presently available ESAs.

Topics: Anemia; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Humans; Observational Studies as Topic; Prolyl-Hydroxylase Inhibitors; Randomized Controlled Trials as Topic

Erythroid stimulating agents (ESAs) have pleiotropic effects, and in animal and human studies those exposed to high erythropoietin had lower blood glucose.. To determine the association between ESA and glucose in anemia-treated patients with myelodysplastic syndromes (MDS) or multiple myeloma (MM).. Patients' glucose levels were compared while on to while off ESA, and all served as their own controls. To test the association between ESA and blood glucose, we employed a linear mixed model, accounting for variability in the number of measurements for each patient.. Charts of 20 patients were reviewed. Mean age was 77 ± 9.8 years (range 50-91). Thirteen patients had MDS, and 8 had MM (1 with both). Glucose (mean ± standard error of the mean) was 116.38 ± 5.21 mg/dL without ESA, as opposed to 105.64 ± 5.11 mg/dL with ESA (p < 0.0001). The 3 diabetic and 5 steroid-treated patients also demonstrated reduced glucose by approximately 19 mg/dL with ESA (p = 0.003 and p = 0.0001, respectively). There was no difference in collective hemoglobin levels between the 2 groups.. ESA treatment for anemia is associated with lower blood glucose in hematologic patients. In those who also have diabetes mellitus, ESA might contribute to glucose control, and even to hypoglycemia. Glucose monitoring is thus advised. Further studies with both diabetic and nondiabetic patients are needed to clarify this association and underlying mechanisms.

Topics: Aged; Aged, 80 and over; Anemia; Blood Glucose; Darbepoetin alfa; Epoetin Alfa; Female; Humans; Male; Middle Aged; Multiple Myeloma; Myelodysplastic Syndromes

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Network Meta-Analysis; Prolyl-Hydroxylase Inhibitors; Renal Dialysis; Renal Insufficiency, Chronic

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Network Meta-Analysis; Prolyl-Hydroxylase Inhibitors; Renal Dialysis; Renal Insufficiency, Chronic

Risk evaluation and mitigation strategy (REMS) programs are intended to improve safe use of US Food and Drug Administration-approved drugs. However, controversy exists over whether they consistently accomplish this goal.. We aimed to assess how initiation of the erythropoiesis stimulating agents (ESAs) darbepoetin alfa and epoetin alfa changed following implementation and enforcement (following a 1-year post-implementation grace period) of a prominent REMS program warning physicians against use in cancer patients with hemoglobin above 10 g/dL.. Using claims data from a large US commercial insurance company, we conducted interrupted time-series analyses of darbepoetin alfa and epoetin alfa initiation among adult cancer patients in the 12 months before REMS program implementation, after REMS program implementation, and after REMS program enforcement. We also evaluated differences in inappropriate initiation (hemoglobin tests all above 10 g/dL in the prior month) between the periods.. In total, we identified 3456 darbepoetin alfa initiators and 2632 epoetin alfa initiators. Over the study period, the monthly number of initiators per 100,000 patients with cancer fell from 119 to 32 for darbepoetin alfa and from 82 to 34 for epoetin alfa. However, non-significant post-REMS program implementation level and slope changes per 100,000 adult patients with cancer were observed for darbepoetin alfa (level 0.03 [95% confidence interval (CI) -14.98 to 15.05]; slope 1.94 [95% CI -0.22 to 4.10]) and epoetin alfa (level -4.10 [95% CI -16.85 to 8.65]; slope -0.52 [95% CI -2.35 to 1.32]). Non-significant post-REMS program enforcement level and slope changes were also seen for both drugs (darbepoetin alfa level 1.58 [95% CI -0.58 to 3.74, slope -0.28 [95% CI -15.29 to 14.73]; epoetin alfa level 1.58 (95% CI -0.26 to 3.42], slope 5.74 [95% CI -7.01 to 18.49]). Finally, non-significant changes in inappropriate darbepoetin alfa (60% vs. 53% vs. 57%, p = 0.68) and epoetin alfa (53% vs. 53% vs. 46%, p = 0.41) initiation were observed between the three study periods.. REMS program implementation and enforcement were not associated with significant changes in ESA initiation, adding to concerns over the degree to which certain REMS programs enhance patient safety.

Topics: Adult; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Risk Evaluation and Mitigation

Variation in de-adoption of ineffective or unsafe treatments is not well-understood. We examined de-adoption of erythropoiesis-stimulating agents (ESA) in anemia treatment among patients with chronic kidney disease (CKD) following new clinical evidence of harm and ineffectiveness (the TREAT trial) and the FDA's revision of its safety warning.. We used a segmented regression approach to estimate changes in use of epoetin alfa (EPO) and darbepoetin alfa (DPO) in the commercial, Medicare Advantage (MA) and Medicare fee-for-service (FFS) populations. We also examined how changes in both trends and levels of use were associated with physicians' characteristics.. Use of DPO and EPO declined over the study period. There were no consistent changes in DPO trend across insurance groups, but the level of DPO use decreased right after the FDA revision in all groups. The decline in EPO use trend was faster after the TREAT trial for all groups. Nephrologists were largely more responsive to evidence than primary care physicians. Differences by physician's gender, and age were not consistent across insurance populations and types of ESA.. Physician specialty has a dominant role in prescribing decision, and that specializations with higher use of treatment (nephrologists) were more responsive to new evidence of unsafety and ineffectiveness.

Topics: Anemia; Darbepoetin alfa; Diffusion of Innovation; Epoetin Alfa; Hematinics; Humans; Practice Guidelines as Topic; Practice Patterns, Physicians'; Regression Analysis; Renal Insufficiency, Chronic; Safety-Based Drug Withdrawals; United States; United States Food and Drug Administration

Pre-operative anaemia treatment has been associated with reduced morbidity in joint arthroplasty. This study examined the impact of a surgical prescription of epoetin (EPO) in contemporary total hip arthroplasty (THA).. We conducted a comparative study in a series of 1402 primary THAs performed in patients all having a pre-operative haemoglobin (Hb) level documented four to eight  weeks before THA surgery. In group A (647 hips), one subcutaneous injection of 40,000 IU EPO once a week for four weeks was prescribed at the discretion of anaesthetist during the pre-operative visit in patients with pre-operative Hb between 10 and 13 g/dl. In group S comprising the remaining 755 hips, an amended EPO therapy including two  injections of 20,000 to 40,000 IU was prescribed by the surgeon in patients with Hb less than 12 g/dl deemed at high risks to be transfused following THA. Primary study endpoint was the bleeding index (BI).. EPO therapy was delivered in 43 patients (6.7%) in group A and in 26 patients (3.4%) in group S (p = 0.006). The mean total dose of EPO administrated was 115,349 IU in group A versus 75,200 IU in group S (p < 0.001). The mean BI were 2.7 ± 1.0 in group A and 2.8 ± 1.0 g/dl in group S (p = 0.375). No patient was blood-transfused up to post-operative day seven in group S versus five patients in group A (p = 0.021).. The amended protocol does not lead to increased peri-operative bleeding. Advances in intra-operative methods to reduce the bleeding allow changing indications of EPO in patients undergoing THA with a low level of Hb.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anemia; Arthroplasty, Replacement, Hip; Blood Transfusion; Epoetin Alfa; Female; Hematinics; Humans; Injections, Subcutaneous; Iron Compounds; Joint Diseases; Male; Middle Aged; Prospective Studies

Switching between different erythropoiesis-stimulating agents (ESAs) during the first year of therapy is frequent (15-20%), much more so toward reference products than biosimilars. The objectives of this study were to investigate the frequency and identify the potential predictors of switching between biosimilar and originator ESAs during the first year of treatment in patients with chronic kidney disease (CKD), or chemotherapy-related anemia from six large Italian geographic areas in the years 2009-2015.. A retrospective cohort study was conducted using six Italian regional claims databases (≥ 13 million inhabitants) during 2009-2015. Among incident epoetin users, the frequency of single, multiple, and backward switch during the first year of treatment was evaluated. Using frailty Cox models, potential predictors of first switch were identified. All analyses were stratified by the main indications for use.. Among 102,240 incident epoetin users, 15,853 (15.5%) switched to another epoetin during the first year of therapy; only 18% of these switched to biosimilars. Single switch was more common (62.2% of the switchers) than multiple (23.5%) or backward switch (14.3%). In cancer, the cumulative number of transfusions and iron preparations dispensed, as well as hyperparathyroidism, were predictors of switching. In CKD, the cumulative number of transfusions, number of vitamin A/D preparations dispensed, and CKD severity increased the probability of switching.. Switching between ESAs was frequent in both CKD and cancer patients. The number of cumulative transfusions and severity of disease seemed to affect the switch.

Topics: Aged; Anemia; Biosimilar Pharmaceuticals; Cohort Studies; Databases, Factual; Epoetin Alfa; Erythropoiesis; Female; Hematinics; Humans; Italy; Male; Neoplasms; Proportional Hazards Models; Renal Insufficiency, Chronic; Retrospective Studies

A multicenter cohort study.The DialysisNet was previously developed for the management of hemodialysis (HD) patients based on the American Society for Testing and Materials Continuity of Care Records by metadata transformation. DialysisNet is a dialysis patient management program created by using the personal health record care platform to overcome the problems of registry studies, in real-time.Here, we aimed to investigate the pattern of treatment for renal anemia in HD patients using DialysisNet.We performed a multicenter cohort study among HD patients who were treated at one of the three Korean university-affiliated hospitals from January 2016 to December 2016. Subjects were divided into 4 hemoglobin variability groups by quartiles. The variable anemia treatment pattern was reviewed. To determine renal anemia treatment patterns, we automatically collected information on the practice of anemia treatment patterns such as erythropoietin stimulating agent (ESA) doses and administration frequencies, and targeted hemoglobin maintenance rate. Individual hemoglobin variabilities were expressed as (standard deviations)/(√(n/[n-1]).The records of 159 patients were analyzed (Hospital A: 35, Hospital B: 21, Hospital C: 103). Mean patients' age was 65.6 ± 12.8 years, and 61.6% were men. Overall, hemoglobin level was 10.5[7.43;13.93] g/dL. 158 (99.3%) patients were using ESA; and overall, the epoetin alfa dose was 33,000[4000;136,800] U per week. Hemoglobin levels (P = .206) and epoetin alfa doses were similar (P = .924) for patients with different hemoglobin variabilities. The hemoglobin target maintenance rate was lower in the highest hemoglobin variability group than in the lowest variability group (P = .045).In this study, detailed information on the actual anemia treatment patterns were obtained using the DialysisNet. We expect that DialysisNet will simplify and improve the renal anemia management for both dialysis patients and health care providers.

Topics: Aged; Anemia; Databases, Factual; Dose-Response Relationship, Drug; Electronic Health Records; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Renal Dialysis; United States

Shortened red blood cell (RBC) lifespan is one of the major factors contributing to anemia in end-stage renal disease (ESRD) patients and should be taken into account in anemia management protocols. In this study, we aimed to estimate RBC lifespan and the source of between-subject variability in ESRD patients. The resulting individual parameters (empirical Bayes estimates) were used to predict hemoglobin concentrations 2 weeks in advance. The reticulocyte-based estimation of RBC lifespan (REBEL) and the population modeling of RBC count data were used. A total of 120 blood samples collected biweekly over 10 weeks in 24 patients receiving maintenance doses of recombinant human erythropoietin (rHuEPO) subcutaneously were included in this analysis. Typical RBC lifespan was estimated to be 63.3 days. RBC lifespan was found to increase with erythroferrone, a recently identified hormone participating in iron metabolism. Approximately, a 10% increase in plasma erythroferrone was associated with a 5% increase in RBC lifespan. In addition, RBC lifespan was 18.7% shorter in females compared with males. Out of 24 subjects, 16 had hemoglobin concentrations predicted within 95% prediction intervals. The median absolute prediction error was 15.9% (interquartile range, 9.5 to 24.7%). We demonstrated that REBEL coupled with the population modeling technique can be used effectively to estimate RBC lifespan. Then, individual parameters can be used to predict future hemoglobin concentrations in ESRD patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Biomarkers; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peptide Hormones; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Reticulocyte Count; Reticulocytes; Time Factors; Treatment Outcome; Young Adult

The ability to control dosage regimens of erythropoiesis-stimulating agents (ESAs) to maintain a desired hemoglobin (HGB) target is still elusive. We utilized a Bayesian approach and informative priors to characterize HGB profiles, using simulated drug concentrations, in patients with end-stage renal disease receiving maintenance doses of epoetin alfa. We also demonstrated an adaptive Bayesian method, applied to individual patients, to improve the accuracy of HGB predictions over time. The results showed that sparse HGB data from daily clinical practice were characterized successfully. The adaptive Bayesian method effectively improved the accuracy of HGB predictions by updating the individual model with new data accounting for within-subject changes over time. The Bayesian approach presented leverages existing knowledge of the model parameters and has a potential utility in clinical practice to individualize dosage regimens of epoetin alfa and ESAs to achieve target HGB. Further studies are warranted to develop an application for practical use.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Anemia; Bayes Theorem; Dose-Response Relationship, Drug; Drug Development; Drug Discovery; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Retrospective Studies

Despite the evolution of blood management protocols, total knee arthroplasty (TKA) occasionally requires allogeneic blood transfusion. This poses a particular challenge for Jehovah's Witnesses (JW) who believe that the Bible strictly prohibits the use of blood products. The aim of this study was to compare JW and a matched-control cohort of non-JW candidates undergoing TKA to assess the safety using modern blood management protocols. Fifty-five JW patients (63 knees) who underwent TKA at our institution between 2005 and 2017 were matched to 63 non-JW patients (63 knees). Patient demographics, intraoperative details, and postoperative complications including in-hospital complications, revisions, and 90-day readmissions were collected and compared between the groups. Additionally, subgroup analysis was performed comparing JW patients who were administered tranexamic acid (TXA) between the two groups. Baseline demographics did not vary significantly between the study cohorts. The mean follow-up was 3.1 years in both the JW and non-JW cohorts. Postoperative complications, including in-hospital complications (7.9 vs. 4.8%;

Topics: Aged; Aged, 80 and over; Anemia; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Blood Transfusion; Epoetin Alfa; Female; Folic Acid; Hematinics; Hemoglobins; Hemostasis, Surgical; Humans; Iron Compounds; Jehovah's Witnesses; Male; Middle Aged; Postoperative Hemorrhage; Preoperative Care; Retrospective Studies; Tranexamic Acid; Treatment Outcome

Intravenous iron and erythropoiesis-stimulating agents are used to manage anemia in chronic hemodialysis patients. The interchangeability between intravenous iron sucrose preparations is still debated. We evaluated how cost and effectiveness were impacted when chronic hemodialysis patients were switched from an original iron sucrose product to an iron sucrose similar preparation.. A single center sequential observational retrospective study was conducted at a French hospital. The same patients were followed during two 24-week periods (iron sucrose in period P1; and iron sucrose similar in period P2). Anemia-related treatment costs were assessed in P1 and P2 from a hospital perspective. Sensitivity analyses were performed to assess the robustness of the results.. Our study included 109 patients (105 analyzed patients and 4 patients with missing data). The mean hemoglobin level was not different between P1 and P2 (p = 0.92). The mean differential cost per patient was + €13.90 (P2 - P1). The factors with the biggest impact on this result were the prices of epoetin alfa and iron sucrose.. This cost minimization analysis suggests that for chronic hemodialysis patients, iron sucrose and iron sucrose similar have the same efficacy and that using iron sucrose similar was more expensive in 66.7% of iterations.

Topics: Administration, Intravenous; Aged; Anemia; Costs and Cost Analysis; Drug Costs; Epoetin Alfa; Female; Ferric Oxide, Saccharated; France; Hematinics; Humans; Male; Middle Aged; Renal Dialysis; Retrospective Studies

Anemia management with erythropoiesis stimulating agents is a challenging task in hemodialysis patients since their response to treatment varies highly. In general, it is difficult to achieve and maintain the predefined hemoglobin (Hgb) target levels in clinical practice. The aim of this study is to develop a fully personalizable controller scheme to stabilize Hgb levels within a narrow target window while keeping drug doses low to mitigate side effects. First in-silico results of this framework are presented in this paper. Based on a model of erythropoiesis we formulate a non-linear model predictive control (NMPC) algorithm for the individualized optimization of epoetin alfa (EPO) doses. Previous to this work, model parameters were estimated for individual patients using clinical data. The optimal control problem is formulated for a continuous drug administration. This is currently a hypothetical form of drug administration for EPO as it would require a programmable EPO pump similar to insulin pumps used to treat patients with diabetes mellitus. In each step of the NMPC method the open-loop problem is solved with a projected quasi-Newton method. The controller is successfully tested in-silico on several patient parameter sets. An appropriate control is feasible in the tested patients under the assumption that the controlled quantity is measured regularly and that continuous EPO administration is adjusted on a daily, weekly or monthly basis. Further, the controller satisfactorily handles the following challenging problems in simulations: bleedings, missed administrations and dosing errors.

Topics: Anemia; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Computer-Assisted; Epoetin Alfa; Erythropoiesis; Hematinics; Hemoglobins; Humans; Infusion Pumps; Models, Biological; Nonlinear Dynamics; Renal Dialysis

Topics: Anemia; Cross-Sectional Studies; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Health Personnel; Hematinics; Humans; Male; Panama; Polyethylene Glycols; Renal Dialysis; Renal Insufficiency, Chronic; Time Factors

Real-world data on the comparative effectiveness and safety of switching among different epoetins (including originators and biosimilars) are limited. In light of current debate about interchangeability, prescribers, some patient groups and decision makers are calling for additional post-marketing evidence on the clinical effects of switching between originator and biosimilar epoetins in chronic kidney disease (CKD) patients.. The objective of this study was to evaluate the effectiveness and safety of switching versus non-switching and of switching from originator/biosimilar epoetin alpha (ESA α) to any other epoetin in CKD patients.. An observational, record-linkage, multi-database, retrospective cohort study was carried out in four Italian geographical areas. All subjects with at least one ESA α dispensing between 1 January 2009 and 31 December 2015 were retrieved. Switching was defined as any transition between originator/biosimilar ESA α to any other epoetin in a series of two consecutive prescriptions up to 2 years. Switchers were matched 1:1 with non-switchers by baseline propensity score and by duration of ESA α treatment. Switchers and non-switchers were followed up from switching date to a maximum of 1 year. Lack of effectiveness and safety of switching versus non-switching were evaluated through Cox regression models (hazard ratio [HR], 95% confidence interval [CI]). A direct comparison between the two switcher categories (switchers from originator/biosimilar ESA α to any other epoetin) was also performed.. Overall, 14,400 incident users of ESA α for anaemia due to CKD (61.4% originator, 38.6% biosimilar) were available for analysis. During the follow-up, we found no differences on effectiveness (HR 1.02, 95% CI 0.79-1.31 originators; HR 1.16, 95% CI 0.75-1.79 biosimilars) and safety outcomes (HR 1.08, 95% CI 0.77-1.50 originators; HR 1.20, 95% CI 0.66-2.21 biosimilars) between switchers and non-switchers of ESA α. Cumulative probabilities of recording an adverse event, either in terms of lack of effectiveness or safety issue, were the same for two switching categories CONCLUSIONS: In this large-scale Italian observational multi-database study, switching versus non-switching as well as switching from biosimilar/originator ESA α to any other epoetin in CKD patients is not associated with any effectiveness and safety outcomes.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Biosimilar Pharmaceuticals; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Humans; Italy; Male; Medical Record Linkage; Middle Aged; Product Surveillance, Postmarketing; Propensity Score; Renal Insufficiency, Chronic; Retrospective Studies; Treatment Outcome

Epoetin biosimilars are an alternative to originator erythropoietic agents in the treatment of chemotherapy-induced anaemia; however, their effects in patients with lymphoproliferative disorders remain unclear. This analysis examined the response of patients with lymphoproliferative disorders experiencing chemotherapy-induced anaemia to 4- or 8-week treatment with the biosimilar epoetin alpha. Treatment was initiated at first occurrence of haemoglobin (Hb) < 10 g/dL during chemotherapy and was stopped when Hb was >11 g/dL, when chemotherapy was completed, or in case of transfusion dependency. Response to epoetin alpha was defined as an increase in Hb of >1 g/dL or as an Hb > 11 g/dL. Stability was defined as change in Hb of ±1 g/dL, and no response was indicated by a decrease in Hb of >1 g/dL or acquired transfusion dependence. Overall, 65 patients were enrolled (median age 69 years; 47.7% ≥ 70 years old). Mean Hb levels at the initiation of epoetin alpha was 9.3 ± 0.5 g/dL. Mean Hb levels reached 10.7 ± 1.4 and 10.6 ± 1.5 g/dL at weeks 4 and 8, respectively, in patients on first-line chemotherapy and 11.4 ± 1.6 and 9.7 ± 1.3 g/dL in those on a second- or higher-line regimen. Overall, 70.8% of patients responded, 26.1% had stable Hb, and 3.1% did not respond. Delays or interruption of any chemotherapy cycle due to anaemia occurred in 18 patients. The biosimilar epoetin alpha was well tolerated and allowed patients with non-Hodgkin lymphoma or chronic lymphoproliferative disorders to continue their course of chemotherapy by effectively increasing and maintaining adequate concentrations of Hb.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Retrospective Studies; Young Adult

To compare the effectiveness of dynamic anemia management strategies by applying the parametric g-formula to electronic health records.. Patients with end-stage renal disease from the US Renal Data System who had congestive heart failure or ischemic heart disease and were undergoing hemodialysis in outpatient dialysis facilities between 2006 and 2010.. We explicitly emulated a target trial of three ‎erythropoietin dosing strategies (aimed at achieving a low, middle, or high hematocrit) and estimated the observational analog of the per-protocol effect.. Of 156,945 eligible patients, 41,970 died during the 18-month follow-up. Compared to the low-hematocrit strategy, the estimated risk of death was 4.6 (95% CI 4.4-4.9) percentage points higher under the high-hematocrit strategy and 1.8 (95% CI 1.7-1.9) percentage points higher under the mid-hematocrit strategy. The corresponding risk differences for a composite outcome of death and myocardial infarction were similar.. An explicit emulation of a target trial using electronic health records, combined with the parametric g-formula, allowed comparison of real-world dynamic strategies that have not been compared in randomized trials.

Topics: Anemia; Dose-Response Relationship, Drug; Electronic Health Records; Epoetin Alfa; Heart Failure; Hematocrit; Humans; Kidney Failure, Chronic; Myocardial Ischemia; Outcome and Process Assessment, Health Care; Randomized Controlled Trials as Topic; Renal Dialysis; Research Design

To assess real-world effectiveness and safety of intravenous (IV) HX575, a biosimilar epoetin-α, in hemodialysis (HD) patients.. This prospective, observational, pharmacoepidemiological study of adult HD patients treated with IV HX575 for renal anemia for up to 24 months was conducted in 114 centers in 10 European countries. Of 2,086 enrolled subjects (safety sample), 2,023 had ≥ 1 follow-up visit (effectiveness sample).. Most (59.3%) patients were male, median age was 68 years. At enrollment, most (82.5%) had been treated with an erythropoiesis-stimulating agent, and 73.0% had adequate iron stores. At baseline, mean (± standard deviation) baseline hemoglobin (Hb) was 11.09 (± 1.14) g/dL and HX575 dose 106.5 (± 78.7) international units (IU)/kg/week; at month 24, Hb was 11.25 (± 1.19) g/dL and HX575 dose 113.0 (± 102.5) IU/kg/week. Variations in mean HX575 dose and Hb over the study were not statistically significant. As to safety, 140 patients (6.7%) experienced ≥ 1 adverse event; of these, 19 events (16 patients; 0.8%) were related to HX575 treatment, 148 (108 patients; 5.2%) were reported as serious, including 12 events in 11 patients (0.5%) stated to be related. No cases of anti-epoetin antibodies or pure red cell aplasia were reported.. MONITOR-CKD5 confirmed the real-world effectiveness and safety profile of IV biosimilar HX575. HD patients treated for up to 24 months showed stable dosing patterns and Hb outcomes. The safety profile of HX575 is likewise comparable to reference epoetin-α.
.

Topics: Aged; Anemia; Biosimilar Pharmaceuticals; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Prospective Studies; Renal Dialysis

The aim of this multicenter prospective study was to evaluate efficacy and safety of biosimilar erythropoiesis-stimulating agents (ESAs) vs originator, based on data from clinical practice in patients with chronic kidney disease (CKD).. We collected data of the patients with diagnosis of CKD on conservative treatment from nine Italian structures. Patients were enrolled applying different exclusion criteria, and various individual parameters were registered at the beginning for descriptive analysis. Patients were treated with epoetin alfa, beta, and darbepoetin as originator and epoetin zeta as biosimilar. Hemoglobin levels have been analyzed at baseline and after 3, 6, and 12 months. Descriptive statistics were used to analyze the results.. At baseline, 47 patients were in the biosimilar group and 57 in the originator; the basal level of hemoglobin was similar between the groups (mean Hb 9.4 and 9.3 g/dL, respectively). Median age, weight, and comorbidities were almost comparable. After 3 months, 44 patients remained in the biosimilar group and 48 in the originator; hemoglobin increase was significantly greater in patients treated with biosimilar [absolute increase 1.6 vs 1.0 g/dL, p < 0.001]. After 6 and 12 months, number of patients fall furthermore. Hemoglobin levels increased more in the biosimilar group after 6 months (2.1 vs 1.1 g/dL, p < 0.001) and 12 months (2.0 vs 1.0 g/dL, p < 0.001).. Biosimilar ESAs have similar risk/benefit profile compared to originators. Our data are in agreement with relevant scientific literature and, on the other hand, they are in contrast with common thought that considers biosimilar less efficacious and less safe than originators.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Biosimilar Pharmaceuticals; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Recombinant Proteins; Renal Insufficiency, Chronic; Risk Assessment; Treatment Outcome

Iron plays vital roles in the human body including enzymatic processes, oxygen-transport via hemoglobin and immune response. Iron metabolism is characterized by ~95% recycling and minor replenishment through diet. Anemia of chronic kidney disease (CKD) is characterized by a lack of synthesis of erythropoietin leading to reduced red blood cell (RBC) formation and aberrant iron recycling. Treatment of CKD anemia aims to normalize RBC count and serum hemoglobin. Clinically, the various fluxes of iron transport and accumulation are not measured so that changes during disease (e.g., CKD) and treatment are unknown. Unwanted iron accumulation in patients is known to lead to adverse effects. Current whole-body models lack the mechanistic details of iron transport related to RBC maturation, transferrin (Tf and TfR) dynamics and assume passive iron efflux from macrophages. Hence, they are not predictive of whole-body iron dynamics and cannot be used to design individualized patient treatment. For prediction, we developed a mechanistic, multi-scale computational model of whole-body iron metabolism incorporating four compartments containing major pools of iron and RBC generation process. The model accounts for multiple forms of iron in vivo, mechanisms involved in iron uptake and release and their regulation. Furthermore, the model is interfaced with drug pharmacokinetics to allow simulation of treatment dynamics. We calibrated our model with experimental and clinical data from peer-reviewed literature to reliably simulate CKD anemia and the effects of current treatment involving combination of epoietin-alpha and iron dextran. This in silico whole-body model of iron metabolism predicts that a year of treatment can potentially lead to 90% downregulation of ferroportin (FPN) levels, 15-fold increase in iron stores with only a 20% increase in iron flux from the reticulo-endothelial system (RES). Model simulations quantified unmeasured iron fluxes, previously unknown effects of treatment on FPN-level and iron stores in the RES. This mechanistic whole-body model can be the basis for future studies that incorporate iron metabolism together with related clinical experiments. Such an approach could pave the way for development of effective personalized treatment of CKD anemia.

Topics: Anemia; Biological Transport, Active; Bone Marrow; Cation Transport Proteins; Computational Biology; Epoetin Alfa; Erythrocytes; Erythropoietin; Hepcidins; Humans; Iron; Iron-Dextran Complex; Liver; Models, Biological; Mononuclear Phagocyte System; Renal Insufficiency, Chronic; Transferrin

Anemia is an inevitable complication of hemodialysis, and the primary cause is erythropoietin deficiency. After diagnosis, treatment begins with an erythropoiesis-stimulating agent (ESA). However, some patients remain anemic even after receiving this medication. This study aimed to investigate the factors associated with resistance to recombinant human erythropoietin therapy with epoetin alfa (αEPO). We performed a prospective, longitudinal study of hemodialysis patients receiving treatment with αEPO at our reference hospital from July 2015 to June 2016. Clinical data was collected, and the response to αEPO treatment was evaluated using the erythropoietin resistance index (ERI). The ERI was defined as the weekly weight-adjusted αEPO dose (U/kg per week)/hemoglobin level (g/dL). A longitudinal linear regression model was fitted with random effects to verify the relationships between clinical and laboratory data and ERI. We enrolled 99 patients (average age, 45.7 (±17.6) years; male, 51.5%; 86.8% with hypertension). The ERI showed a significant positive association with serum ferritin and C-reactive protein, percentage interdialytic weight gain, and continuous usage of angiotensin receptor blocker (ARB) hypertension medication. The ERI was negatively associated with serum iron and albumin, age, urea reduction ratio, and body mass index. Our findings indicate that resistance to αEPO was related to a low serum iron reserve, an inflammatory state, poor nutritional status, and continuous usage of ARBs.

Topics: Adult; Anemia; Body Mass Index; Drug Resistance; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Iron; Linear Models; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Reference Values; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Time Factors; Treatment Outcome

The US Food and Drug Administration (FDA) has approved epoetin and darbepoetin for chemotherapy-induced anemia (CIA). Approved epoetin and darbepoetin dosing schedules were three times per week and weekly, respectively, although off-label, less frequent scheduling was common. In 2004, 2007, and 2008, a US Food and Drug Administration Advisory Committees warned of risks associated with erythropoiesis-stimulating agents. During this period, lawsuits alleging illegal darbepoetin marketing practices have concluded, resulting in $1.1 billion in fines and settlements and one criminal conviction. No prior study, to our knowledge, has reported on the use of darbepoetin versus epoetin for CIA.. We evaluated the dosing, utilization, and costs of erythropoiesis-stimulating agents among 3,761 South Carolina Medicaid patients with CIA.. Epoetin and darbepoetin utilization rates were 22% and 28% in 2003, 10% and 33% in 2007, and 3% and 7% in 2010, respectively. Mean per-patient per-administration epoetin and darbepoetin doses were 40,983 IU and 191 µg, respectively, in 2003 and 47,753 IU and 369 µg, respectively, in 2010. Mean monthly patient costs for epoetin and darbepoetin were $1,030 and $981, respectively, in 2003 and $932 and $1,352, respectively, in 2010. Epoetin use decreased steadily between 2002 and 2010; darbepoetin use increased steadily between 2003 and 2007 and then decreased steadily thereafter. Per-patient dosing of darbepoetin, but not epoetin, increased steadily between 2003 and 2010, and monthly per-patient epoetin costs decreased 3% while the per-patients costs of darbepoetin increased 30% between 2003 and 2010.. To our knowledge, our findings are the first data reporting on epoetin versus darbepoetin use for CIA and support recently concluded lawsuits involving allegations of illegal marketing practices of the manufacturer of darbepoetin.

Topics: Adolescent; Adult; Anemia; Antineoplastic Agents; Breast Neoplasms; Colorectal Neoplasms; Darbepoetin alfa; Drug Utilization; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Logistic Models; Lung Neoplasms; Male; Medicaid; Middle Aged; Recombinant Proteins; South Carolina; United States; Young Adult

Topics: Aged; Anemia; Biomarkers; Drug Resistance; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Hyperparathyroidism; Kidney Failure, Chronic; Parathyroid Hormone; Parathyroidectomy; Renal Dialysis; Severity of Illness Index; Treatment Outcome

Several treatment modalities exist for the treatment of perioperative anemia. We determined the effect of oral iron supplementation on preoperative anemia, and the use of blood-conserving interventions before total hip arthroplasty (THA) and total knee arthroplasty (TKA).. A total of 3435 total joint arthroplasties (1461 THAs and 1974 TKAs) were analyzed during 2 phases of a blood conservation program. The first phase used erythropoietin alfa (EPO) or intravenous (IV) iron for patients at risk for perioperative anemia. The second phase included these interventions, as well as preoperative iron supplementation. The effect on preoperative hemoglobin (Hb) and serum ferritin, as well as EPO and IV iron utilization, was determined.. Oral iron therapy increased preoperative Hb level by 6 g/L (P < .001) and 7 g/L (P < .001) in the hip and knee cohorts, respectively. Serum ferritin level rose by 80 μg/L (P < .001) and 52 μg/L (P < .001) in the hip and knee cohorts, respectively. The number of patients with an Hb level <130 g/L was significantly reduced (P < .001 for both cohorts), as were patients with serum ferritin levels <35 μg/L (P = .002 for hip and P < .001 for knee cohorts). Utilization of EPO reduced from 16% to 6% (P < .001) and 18% to 6% (P < .001) in the hip and knee cohorts, respectively. Utilization of IV iron reduced from 4% to 2% (P = .05) and 5% to 2% (P < .001) in the hip and knee cohorts, respectively.. Oral iron therapy reduced the burden of perioperative anemia and reduced utilization of other blood-conserving therapies before THA and TKA. Future research should delineate the cost-effectiveness of oral iron therapy.

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Anemia; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Transfusion; Bloodless Medical and Surgical Procedures; Cost-Benefit Analysis; Dietary Supplements; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Iron; Joint Diseases; Male; Middle Aged; Preoperative Care

Hypothesizing that statins may be useful as adjuvant treatment for renal anemia, we examined the association between statin prescription (Rx) and erythropoiesis-stimulating agent (ESA) hyporesponsiveness in Japanese hemodialysis (HD) patients prescribed ESAs.. We examined 3,602 patients in 60 HD facilities dialyzed 3 times/week for ≥4 months from the Japan Dialysis Outcomes and Practice Patterns Study phases 3-5 (2005-2015). Statin Rx was reported at the end of a 4-month interval (baseline) for each patient. ESA hyporesponsiveness in the subsequent 4 months was then defined as a binary indicator (mean hemoglobin [Hgb] level <10 g/dL and mean ESA dose >6,000 units/week) and separately as the ESA resistance index (ERI; mean ESA dose/[dry weight × mean Hgb]). We used adjusted logistic and linear regressions to evaluate the associations between statin Rx and ESA hyporesponsiveness.. At baseline, 16.2% of patients reported statin Rx; 12.8% were classified as having ESA hyporesponsiveness during 4 months of follow-up. Compared to patients without statin Rx, patients with statin Rx had lower odds of ESA hyporesponsiveness (OR 0.87; 95% CI 0.66-1.15). Similarly, the ERI was lower for those with statin Rx than without (ratio of means, 0.94; 95% CI 0.89-0.99) after adjustment for possible confounders.. Our results suggest that statins may slightly reduce ESA hyporesponsiveness in HD patients. However, any causal inference is limited by the observational study design and unmeasured compliance with statin Rx.

Topics: Aged; Anemia; Cardiovascular Diseases; Chemotherapy, Adjuvant; Drug Resistance; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Random Allocation; Renal Dialysis; Treatment Outcome

To assess the safety and immunogenicity of subcutaneous (SC) HX575 (epoetin-α) in dialysis- and nondialysis-dependent adult patients with chronic kidney disease (CKD).. Open-label, single-arm, multicenter study in patients (n = 416) from Germany, Italy, Poland, Romania, Russia, Turkey, and Ukraine.. Mean (standard deviation (SD)) age was 52.3 (15.8) years, all patients were Caucasian, and similar proportions were male/female. 250 patients (60.1%) were erythropoiesis-stimulating agent (ESA)-naïve, and 166 (39.9%) were receiving ESA maintenance therapy at study start; mean (SD) on-study treatment duration with HX575 was 43.4 (15.8) weeks and 45.3 (13.7) weeks, respectively. Binding antierythropoietin (EPO) antibodies were detected by radioimmunoprecipitation (RIP) assay in 7 patients (1.7%; incidence 0.019); 5 of these were ESA-naïve at study entry. No patient developed neutralizing antibodies as determined in a cell-based epoetin neutralizing assay. Of the 7 patients with a positive binding anti-EPO RIP assay, 4 tested negative at later time points while continuing HX575 treatment. Three patients had low titers of anti-EPO antibodies at the last study assessment. There were no clinical signs of immunogenicity or hypersensitivity.. SC HX575 was effective for correcting and maintaining correction of anemia, and the mean weekly dose remained stable over time.
.

Topics: Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Europe; Female; Hematinics; Humans; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

In the general population, haemoglobin (Hb) concentration is higher in men than in women. However, target Hb levels in dialysis patients are set constant regardless of the patient's sex. The aim of this study was to evaluate Hb concentration and the use of erythropoiesis-stimulating agents (ESA) in peritoneal dialysis (PD) patients taking gender and dialysis adequacy into account.. The study comprised two parts. The first was a cross-sectional analysis of Hb and ESA in 2180 prevalent PD patients. The second included 88 incident PD patients, followed for 36 months. During this time, the major parameters recorded at 12-month intervals included: Hb concentration, weekly ESA, total, renal, and peritoneal Kt/V. Erythropoietin resistance index (ERI) was calculated as the ratio between ESA dose and achieved Hb.. In prevalent PD patients, Hb concentration was significantly lower in women, (11.2 ± 1.4 vs. 11.5 ± 1.6 g/dl; p < 0.001), despite higher doses of ESA (2691 ± 1821 vs. 2344 ± 1422; p = 0.001). Hb concentrations were related to dialysis adequacy in both cohorts. However, despite significantly higher Kt/V, women were characterized by a lower Hb level. In incident patients, this association was present throughout the observation period, while the ESA dose in women was significantly higher at every time point. In multiple regression analysis, gender was an independent determinant of ERI (b = 0.34; p < 0.05).. Despite higher dialysis adequacy, Hb concentration in women treated with PD is significantly lower, and the ability to correct it impaired, as compared to men.

Topics: Aged; Anemia; Cross-Sectional Studies; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Prognosis; Registries; Retrospective Studies; Risk Assessment; Sex Factors; Treatment Outcome

Exogenous replacement of erythropoietin (EPO) by recombinant human EPO has been considered a standard of care for the treatment of anemia in patients with chronic kidney disease for more than 20 years. Genetically engineered biologic proteins derived from human, animal, or microorganism sources are a major area of growth in modern medical care, accounting for one-third of new drug approvals in the past decade. Despite benefit to patients, the use of biologics comes at a significant cost, representing one of the fastest growing segments of strained healthcare budgets around the world.. Biosimilars, or biologic drugs that are designed to be highly similar to approved reference biologic drugs, have been available in Europe for more than 10 years with no unusual or unexpected effects compared to their reference biologics whose patents have expired. Given the success of the biosimilar approval pathway pioneered in Europe, it has served as a global reference for other regulatory authorities to establish and implement biosimilar licensure frameworks, including the United States (US), the largest pharmaceutical market in the world. Given 10 of the top 25 drugs sold in 2014 were biologics, and considering the rising costs of healthcare, biosimilars have the potential to become a significant part of the US market. Key Messages: For the nephrology community, the recent patent expiries for epoetin alfa (Epogen®, Amgen and Procrit®, Johnson & Johnson) have created the opportunity to develop biosimilar EPOs. And while no biosimilar in this therapeutic class is approved in the US, there are proposed biosimilars in development.

Topics: Anemia; Animals; Biosimilar Pharmaceuticals; Commerce; Drug Approval; Drug Industry; Epoetin Alfa; Erythropoiesis; Erythropoietin; Europe; Hematinics; History, 20th Century; History, 21st Century; Humans; Kidney; Kidney Diseases; Nephrology; Patient Safety; Recombinant Proteins; Renal Insufficiency, Chronic; United States

Anaemia is a complication reported in up to 70% of the multiple myeloma patients (MM), with remarkable clinical, cognitive and socio-relational consequences. Anaemia relates to the course of MM, normalizing in patients during remission and reappearing in relapsing/non-responding patients. In a pilot study with 31 patients with MM and transfusion-dependent anaemia, we evaluated the effects of Binocrit (biosimilar epoetin alfa) on transfusions, haemoglobin levels, mental status (mini-mental state evaluation) and the patients' social-relational functioning and quality of life (QoL). Within a 12-week interval, patients received 40.000 U Binocrit once a week. Binocrit significantly decreased the incidence of transfusion, regardless of the patients' transfusion history, and significantly increased haemoglobin levels (before-and-after-treatment median haemoglobin values = 8.20 vs. 9.40 g/dl, respectively; Wilcoxon Z test, p < .001). A comparatively greater increment in haemoglobin levels among patients who responded to first vs. additional lines of chemotherapy was also observed. Importantly, we additionally found moderate-to-strong positive associations between increments in haemoglobin levels and corresponding increments both in psychological well-being and QoL (FACT-An scores) and the patients' cognitive status (mini-mental state evaluation scores). After statistically controlling for possible concurrent benefits of anti-myeloma therapy, increments in haemoglobin levels clearly predicted both increments in socio-relational FACT-An scores (Spearman's rho = 0.60, p < .001) and in cognitive functioning scores (Spearman's rho = 0.49, p < .006). Binocrit thus appears as an effective, well-tolerated agent for the management of myeloma anaemia, whose documented benefits include amelioration of anaemia, reduction in transfusion, and improvements in the patients' social-relational functioning and cognitive well-being.

Topics: Aged; Aged, 80 and over; Anemia; Biosimilar Pharmaceuticals; Blood Transfusion; Cognition; Epoetin Alfa; Female; Hemoglobins; Humans; Male; Multiple Myeloma; Pilot Projects; Quality of Life; Treatment Outcome

To evaluate the benefit/risk profile of epoetin α biosimilar with the erythropoiesis-stimulating agents (ESAs) originators when administered to naïve patients from clinical practice.. Population-based observational cohort study.. All residents in the Lazio Region, Italy, with chronic kidney disease (CKD) or cancer retrieved from the Electronic Therapeutic Plan (ETP) Register for ESA between 2012 and 2014.. Overall, 13 470 incident ESA users were available for the analysis, 8161 in the CKD and 5309 in the oncology setting, respectively.. ESAs identified through the ATC B03XA were divided into 3 groups: (1) biosimilars; (2) epoetin α originator and (3) other originators. Patients were exposed to ESAs from the date of activation of the ETP, until the end of a 6-month follow-up period.. Effectiveness (all-cause mortality and blood transfusion) and safety (major cardiovascular events, blood dyscrasia). A composite outcome including all-cause mortality, blood transfusion and major cardiovascular events was predefined. HRs of any outcome were estimated through Cox regression.. We found no differences between patients on biosimilars or all originators with regard to the risk estimates of all-cause mortality, blood transfusion, major cardiovascular events and blood dyscrasia in the CKD setting. The composite outcome confirmed these results (biosimilars vs epoetin α originators: adjusted HR=1.02, 95% CI 0.78 to 1.33; biosimilars vs other originators: adjusted HR=1.09, 95% CI 0.85 to 1.41). Comparable risk estimates were observed between biosimilars and all originators in the oncology setting.. In both settings, our findings are suggestive of no difference between biosimilars and originators on relevant effectiveness and safety outcomes. This study may contribute to settling future drug policy for the health services and provides reassurance on the approval pathway for biosimilars. The oncology setting merits further research, taking into account tumour types, tumour stage and anticancer chemotherapy administered.

Topics: Anemia; Biosimilar Pharmaceuticals; Blood Transfusion; Cardiovascular Diseases; Cause of Death; Epoetin Alfa; Erythropoiesis; Female; Hematinics; Humans; Italy; Male; Neoplasms; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Assessment; Treatment Outcome

Previous research suggests that erythropoiesis stimulating agent (ESA) administration in dialysis is a time-consuming task and switching to less frequently dosed ESAs may offer operational efficiencies. Our objective was to describe and measure the time spent on tasks in the ESA administration process in US dialysis centers, and to estimate potential efficiency gains of using weekly (QW) administration vs three-times-per-week (TIW) administration.. We conducted a time and motion study of staff time required to prepare, administer and document ESA doses. Dialysis centers using intravenous administration of TIW epoetin alfa (EPO) or QW darbepoetin alfa (DPO) were selected in pairs (one EPO, one DPO) from the same organization to help control for differences in ESA protocols and staffing patterns across organizations. ESA-related tasks were timed by trained observers. Time savings of TIW vs QW administration were estimated. Staff were interviewed about alternate activities that could be accomplished if time were saved in the ESA process.. A total of 200 administrations were observed (81 DPO, 119 EPO). A mean of 2.26 (95% CI: 2.1-2.5) minutes per dose were required for ESA administration. ESA process time per administration did not vary significantly between EPO and DPO (p = 0.83). Estimated potential monthly staff time savings for an average facility of 70 patients totaled 23 hours, due to fewer ESA administrations using QW DPO. Patient education and fulfillment of care plans were identified as opportunities for improved care processes that could be implemented if staff time was freed up from the ESA process.. Results should not be generalized to other countries, ESAs and/or dosing frequencies.. Switching from TIW EPO to QW DPO can result in time savings due to fewer administrations and provide opportunities to redirect nurse time towards activities aimed at improving patient care.

Topics: Aged; Anemia; Darbepoetin alfa; Epoetin Alfa; Female; Hematinics; Humans; Male; Middle Aged; Prospective Studies; Renal Dialysis; United States

Controversy exists regarding the renoprotective effect of erythropoiesis-stimulating agent (ESA) in progressive chronic kidney disease (CKD) with renal anemia. In this study, we examined whether ESA therapy has a renoprotective effect in progressive CKD.. The subjects in this retrospective observational study were 68 non-dialysis dependent CKD patients with renal anemia. We compared the progression rate (PR), defined by the slope of the linear regression line of estimated glomerular filtration rate, measured during 6 months just before and after the start of ESA therapy. We also investigated the factors affecting renoprotective efficacy of ESA therapy against the progression of CKD.. Median (interquartile range) PR decreased significantly from 6.2 (3.7-12.7) to 4.0 (-0.3 to 7.3) mL/min/1.73 m(2)/year after the start of ESA therapy. Blood pressure levels and rate of medication with renin-angiotensin system inhibitors were comparable between the two periods. Next, we investigated the factors affecting renoprotective efficacy of ESA therapy against the progression of CKD. Thirty patients were good renal responders, defined as those with the ratio of post-/pre-PR of <0.5 and the difference of pre- minus post-PR >5.0 mL/min/1.73 m(2)/year, and 38 patients were poor renal responders who did not meet the definition of good renal responders. Multivariable logistic regression analysis showed that weekly ESA dose, but not increase in hemoglobin level, was a significant and independent determinant of the renoprotective effect of ESA.. ESA therapy slows the progression of CKD and part of the effect might be attributed to the direct renoprotective action of ESA.

Topics: Aged; Anemia; Blood Pressure; Disease Progression; Epoetin Alfa; Erythropoiesis; Female; Hematinics; Hemoglobins; Humans; Japan; Kidney; Logistic Models; Male; Middle Aged; Multivariate Analysis; Renal Insufficiency, Chronic; Renin-Angiotensin System; Retrospective Studies; Treatment Outcome

Topics: Aged; Aged, 80 and over; Anemia; Anemia, Iron-Deficiency; Biosimilar Pharmaceuticals; Dose-Response Relationship, Drug; Drug Substitution; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Trace Elements

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Kidney

Introduction Preoperative anaemia remains undertreated in the UK despite advice from national agencies to implement blood conservation measures. A local retrospective audit of 717 primary hip/knee replacements in 2008-2009 revealed 25% of patients were anaemic preoperatively. These patients experienced significantly increased transfusion requirements and length of stay. We report the results of a simple and pragmatic blood management protocol in a district general hospital. Methods Since 2010 patients at our institution who are found to be anaemic when listed for hip/knee replacement have been offered iron supplementation and/or erythropoietin depending on haemoglobin and ferritin levels. In this study, postoperative blood transfusions, length of stay and readmissions were assessed retrospectively for all patients undergoing elective primary hip/knee replacement in 2014 and compared with the baseline findings. Results During the 12-month study period, 406 patients were eligible for inclusion and none were excluded. Eighty-nine patients (22%) were anaemic preoperatively and sixty-five received treatment. The transfusion rate fell from the baseline levels of 23.0% and 6.7% to 4.3% and 0.5% for hip and knee replacements respectively (p<0.001). The median length of stay reduced from 6 to 3 days (p<0.001) for both hip and knee replacements. The rate for readmissions within 90 days fell from 13.5% to 8.9% (p<0.05). Conclusions Preoperative anaemia is common in patients listed for hip/knee replacement and it is associated strongly with increased blood transfusion. The introduction of a blood management protocol has led to significant reductions in transfusion and length of stay, sustained over a four-year period. This suggests that improved patient outcomes, conservation of blood stocks and cost savings can be achieved.

Topics: Anemia; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Transfusion; Clinical Protocols; Epoetin Alfa; Ferric Compounds; Ferritins; Hematinics; Hemoglobins; Hospitals, General; Humans; Length of Stay; Maltose; Patient Readmission; Postoperative Complications; Preoperative Care; Retrospective Studies; United Kingdom

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Iron; Neoplasms; Recombinant Proteins; Treatment Outcome

Topics: Anemia; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Standard of Care

Subcutaneous administration of Eprex(®) (epoetin alfa) in patients with chronic kidney disease (CKD) was contraindicated in the European Union between 2002 and 2006 after increased reports of anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA). The Prospective Immunogenicity Surveillance Registry (PRIMS) was conducted to estimate the incidence of antibody-mediated PRCA with subcutaneous administration of a new coated-stopper syringe presentation of Eprex(®) and to compare this with the PRCA incidence with subcutaneous NeoRecormon(®) (epoetin beta) and Aranesp(®) (darbepoetin alfa).. PRIMS was a multicentre, multinational, non-interventional, parallel-group, immunogenicity surveillance registry. Adults with CKD receiving or about to initiate subcutaneous Eprex(®), NeoRecormon(®) or Aranesp(®) for anaemia were enrolled and followed for up to 3 years. Unexplained loss or lack of effect (LOE), including suspected PRCA, was reported, with antibody testing for confirmation of PRCA.. Of the 15 333 patients enrolled, 5948 received Eprex(®) (8377 patient-years) and 9356 received NeoRecormon(®)/Aranesp(®) (14 286 patient-years). No treatment data were available for 29 patients. Among 23 patients with LOE, five cases of PRCA were confirmed (Eprex(®), n = 3; NeoRecormon(®), n = 1; Aranesp(®), n = 1). Based on exposed time, PRCA incidence was 35.8/100 000 patient-years (95% CI 7.4-104.7) for Eprex(®) versus 14.0/100 000 patient-years (95% CI 1.7-50.6) for NeoRecormon(®)/Aranesp(®). The incidence of PRCA with Eprex(®) was not significantly different versus comparator ESAs (rate ratio: 2.56; 95% CI 0.43-15.31). An analysis based on observed time produced similar findings.. This large, prospective registry demonstrates that PRCA is rare with subcutaneous administration of either the new coated-stopper syringe presentation of Eprex(®), or NeoRecormon(®) or Aranesp(®).

Topics: Adult; Aged; Aged, 80 and over; Anemia; Autoantibodies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Humans; Incidence; Male; Middle Aged; Prognosis; Prospective Studies; Recombinant Proteins; Red-Cell Aplasia, Pure; Registries; Risk Assessment; Severity of Illness Index

Biologic drugs, including epoetin, continue to play an important role in the management of medical conditions. However, biologics are costly and soon many of the patents on these drugs will expire, making way for non-brand name products (ie, biosimilars). It is only by introducing competition to the marketplace that costs will de-escalate. In Europe, a specific regulatory pathway for approving biosimilars has been in place since 2005. A similar review pathway in the United States has been developed by the US Food and Drug Administration. These guidelines for approving biosimilars are stringent, requiring preclinical pharmacodynamic and toxicologic studies, clinical studies to demonstrate bioequivalence and efficacy, and long-term postmarketing studies to monitor drug safety. Biosimilar epoetin has been used in Europe since 2007, and a wealth of data has been collected. These studies and reports indicate that the efficacy and safety profiles of biosimilar epoetin are similar to those of originator epoetin alfa. Biosimilars of epoetin alfa are expected to be among the first biosimilar agents to be approved for use in the United States. The availability of lower cost epoetins may have significant impact on the treatment of anemia of chronic kidney disease.

Topics: Anemia; Biosimilar Pharmaceuticals; Drug Approval; Epoetin Alfa; Erythropoietin; Health Care Costs; Hematinics; Humans; Nephrology; Recombinant Proteins; Renal Insufficiency, Chronic; United States; United States Food and Drug Administration

The aim of the US dialysis Prospective Payment System bundle, launched in January 2011, was reduction and more accurate prediction of costs of services, whilst maintaining or improving patient care. Dialysis facilities could either adopt the bundle completely (100%) in the first year of launch, or phase-in (25%) over four years. Differences in practice patterns and patient outcomes were hypothesized to occur in facilities that phased-in 25% compared to those that did not.. Data are from STEPPS, a study of 51 small dialysis organization facilities designed to describe trends in dialytic treatment before and after bundle implementation. Baseline was defined as October-December 2010; follow-up as January-December 2011. Facility- and patient-level data were collected at enrollment and regularly thereafter. Cox proportional hazards and linear multi-level models were used to estimate the effect of opting-in 25% (vs. 100%) on practice patterns and clinical outcomes.. 12 facilities (patient n = 346) opted-in 25% and 37 facilities (patient n = 1296) opted-in 100% to the dialysis bundle. At baseline, patients at 25% facilities were primarily covered by Medicare, were more likely to be black, and were receiving higher monthly epoetin alfa (EPO) doses. Throughout 2011, patients in 100% facilities received lower monthly EPO doses, and had lower mean hemoglobin concentrations; hospitalization and mortality rates were numerically lower in 25% facilities but not statistically different.. The economic pressure for dialysis providers to work within an expanded composite rate bundle whilst maintaining patient care may be a driver of practice indicator outcomes. Additional investigations are warranted to more precisely estimate clinical outcomes in patients attending facilities enrolling into the bundle 100% relative to the previous fee-for-service framework.

Topics: Adult; Aged; Ambulatory Care Facilities; Anemia; Epoetin Alfa; Female; Hematinics; Hospitalization; Humans; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Outcome Assessment, Health Care; Practice Patterns, Physicians'; Proportional Hazards Models; Prospective Payment System; Quality Indicators, Health Care; Renal Dialysis; United States

Adequately powered studies directly comparing hard clinical outcomes of darbepoetin alfa (DPO) versus epoetin alfa (EPO) in patients undergoing dialysis are lacking.. Observational, registry-based, retrospective cohort study; we mimicked a cluster-randomized trial by comparing mortality and cardiovascular events in US patients initiating hemodialysis therapy in facilities (almost) exclusively using DPO versus EPO.. Nonchain US hemodialysis facilities; each facility switching from EPO to DPO (2003-2010) was matched for location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis therapy in these facilities were assigned their facility-level exposure.. DPO versus EPO.. All-cause mortality, cardiovascular mortality; composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke.. Unadjusted and adjusted HRs from Cox proportional hazards regression models.. Of 508 dialysis facilities that switched to DPO, 492 were matched with a similar EPO facility; 19,932 (DPO: 9,465 [47.5%]; EPO: 10,467 [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years during which 5,550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (vs EPO) was 1.06 (95% CI, 1.00-1.13) and was materially unchanged after adjustment for all other baseline characteristics (HR, 1.05; 95% CI, 0.99-1.12). Cardiovascular mortality did not differ between groups (HR, 1.05; 95% CI, 0.94-1.16). Nonfatal outcomes were evaluated among 9,455 patients with fee-for-service Medicare: 4,542 (48.0%) in DPO and 4,913 (52.0%) in EPO facilities. During 10,457 and 10,363 person-years, 248 and 372 events were recorded, respectively, for strokes and MIs. We found no differences in adjusted stroke or MI rates or their composite with cardiovascular death (HR, 1.10; 95% CI, 0.96-1.25).. Nonrandom treatment assignment, potential residual confounding.. In incident hemodialysis patients, mortality and cardiovascular event rates did not differ between patients treated at facilities predominantly using DPO versus EPO.

Topics: Aged; Ambulatory Care Facilities; Anemia; Cardiovascular Diseases; Cause of Death; Comorbidity; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemodialysis Units, Hospital; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Recombinant Proteins; Registries; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Stroke; Treatment Outcome; United States

Topics: Aged; Anemia; Aortic Aneurysm, Abdominal; Blood Loss, Surgical; Critical Illness; Epoetin Alfa; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Iron Compounds; Jehovah's Witnesses; Male; Recombinant Proteins; Salvage Therapy

Recent changes in clinical practice guidelines and reimbursement policies may have affected the use of anemia-related medications and red blood cell (RBC) transfusions in peritoneal dialysis (PD) and hemodialysis (HD) patients. We sought to compare patterns of erythropoiesis-stimulating agents (ESA) and intravenous (IV) iron use, achieved hemoglobin levels, and RBC transfusion use in PD and HD patients.. In quarterly cohorts of prevalent dialysis patients receiving persistent therapy (>3 months), 2007-2011, with Medicare Parts A and B coverage, we assessed ESA and IV iron use and dose, RBC transfusions, and hemoglobin levels. Quarterly transfusion rates were calculated.. Observable PD and HD patients numbered 14,958 and 221,866 in Q1/2007 and 17,842 and 256,942 in Q4/2011. Adjusted ESA use was lower in PD (71.4-80.1%) than in HD (86.9-92.0%) patients, decreasing from 80.1% (Q1/2010) to 71.4% (Q4/2011) in PD patients, and from 92.0 to 86.9% in HD patients. The mean adjusted ESA dose decreased by 67.5% in PD and 58.4% in HD patients. IV iron use tended to increase, peaking at 39.3% for PD (Q3/2011) and 80.5% for HD (Q2/2011) patients. Adjusted mean hemoglobin levels fell from 11.7 to 10.6 mg/dl in PD and from 12.0 to 10.7 mg/dl in HD ESA users; adjusted transfusion rates increased from 2.4 to 3.0 per 100 patient-months in PD and from 2.6 to 3.3 in HD patients.. In patients receiving persistent dialysis, dose and frequency of ESA administrations decreased during the period 2007-2011. Mean hemoglobin levels decreased by more than 1 g/dl, while transfusion rates increased by approximately 25%.

Topics: Adolescent; Adult; Aged; Anemia; Cohort Studies; Epoetin Alfa; Erythrocyte Transfusion; Female; Hematinics; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Practice Patterns, Physicians'; Renal Dialysis; Retrospective Studies; Young Adult

Recombinant human erythropoietin (epoetin) is used routinely to increase blood hemoglobin levels in patients with ESRD and anemia. Although lower doses of epoetin are required to achieve equivalent hemoglobin responses when administered subcutaneously rather than intravenously, standard practice has been to administer epoetin to patients on hemodialysis intravenously. Randomized trials of alternative epoetin treatment regimens in patients with kidney failure have shown that risks of cardiovascular complications and death are related to the dose levels of epoetin used. Therefore, given the dose-sparing advantages of subcutaneous epoetin administration, the possibility that treatment of patients on hemodialysis with subcutaneous epoetin might be associated with more favorable outcomes compared with intravenous treatment was investigated.. A retrospective cohort study of 62,710 adult patients on hemodialysis treated with either intravenous or subcutaneous epoetin-α and enrolled in the Centers for Medicare and Medicaid Services ESRD Clinical Performance Measures Project from 1997 to 2005 was carried out. Risks of death and/or hospitalization for cardiovascular complications (adverse composite event outcomes) during 2 years of follow-up were determined in relationship to epoetin dose and route of administration (intravenous versus subcutaneous) by multivariate Cox proportional hazard modeling adjusted for demographics and clinical parameters.. Epoetin doses used to achieve equivalent hemoglobin responses in study patients were, on average, 25% higher when epoetin was administered intravenously rather than subcutaneously (as expected). Moreover, adverse composite event outcomes were found to be significantly more likely to occur during follow-up for patients on hemodialysis managed with intravenous rather than subcutaneous epoetin (adjusted hazard ratio for adverse events within 1 year [intravenous versus subcutaneous] was 1.11 [95% confidence interval, 1.04 to 1.18]).. This study finds that treatment of patients on hemodialysis with subcutaneous epoetin is associated with more favorable clinical outcomes than those associated with intravenous epoetin treatment.

Topics: Administration, Intravenous; Aged; Anemia; Cardiovascular Diseases; Epoetin Alfa; Female; Heart Failure; Hematinics; Hemoglobins; Hospitalization; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Renal Dialysis; Retrospective Studies; Stroke; United States

Cancer cachexia is a syndrome characterized by loss of skeletal muscle mass, inflammation, anorexia and anemia, contributing to patient fatigue and reduced quality of life. In addition to nutritional approaches, exercise training (EX) has been proposed as a suitable tool to manage cachexia. In the present work the effect of mild exercise training, coupled to erythropoietin (EPO) administration to prevent anemia, has been tested in tumor-bearing mice. In the C26 hosts, acute exercise does not prevent and even worsens muscle wasting. Such pattern is prevented by EPO co-administration or by the adoption of a chronic exercise protocol. EX and EPO co-treatment spares oxidative myofibers from atrophy and counteracts the oxidative to glycolytic shift, inducing PGC-1α. LLC hosts are responsive to exercise and their treatment with the EX-EPO combination prevents the loss of muscle strength and the onset of mitochondrial ultrastructural alterations, while increases muscle oxidative capacity and intracellular ATP content, likely depending on PGC-1α induction and mitophagy promotion. Consistently, muscle-specific PGC-1α overexpression prevents LLC-induced muscle atrophy and Atrogin-1 hyperexpression. Overall, the present data suggest that low intensisty exercise can be an effective tool to be included in combined therapeutic approaches against cancer cachexia, provided that anemia is coincidently treated in order to enhance the beneficial action of exercise.

Topics: Anemia; Animals; Blotting, Western; Cachexia; Disease Models, Animal; Epoetin Alfa; Exercise Therapy; Female; Hematinics; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Electron, Transmission; Muscle, Skeletal; Muscular Atrophy; Neoplasms, Experimental; Physical Conditioning, Animal; Real-Time Polymerase Chain Reaction

Anemia management in hemodialysis patients is of primary importance for clinicians and dialysis providers. Through a retrospective claims analysis, we studied prevalent US hemodialysis patients 1998-2009, and examined patterns of hemoglobin levels and erythropoiesis-stimulating agent (ESA, epoetin [EPO], and darbepoetin [DPO] ) doses surrounding hospitalization events. Medicare outpatient claims were used to determine monthly ESA doses and associated hemoglobin levels. ESA dose trajectories were defined with repeated measures models incorporating an autoregressive covariance matrix that compared subsequent measurements with the index month of hospitalization, with variance component covariance matrices chosen for pair-wise comparisons. Regarding prehospitalization hemoglobin levels, a biphasic pattern occurred in both the EPO (1998-2009, n = 161,242) and DPO (2004-2009, n = 4391) populations; levels rose from 1998 to 2004, fell thereafter in the EPO population, and fell after 2006 or 2007 in the DPO population. In the EPO population, the proportions of patients with hemoglobin less than 10 g/dL were 30.1% in 1998, 14.5% in 2004, and 28.3% in 2009; corresponding values for the DPO population were 21.0% in 2004 and 31.6% in 2009. While some degree of year-to-year variability occurred, EPO dose trends were less pronounced, with an apparent peak in 2004 followed by a modest decline; trends were similar for DPO. Trends in EPO dose trajectories did not completely parallel those for hemoglobin level; while EPO doses increased yearly up to 2004, doses stabilized, but did not materially decrease after 2004. No definite annual trends for DPO dose trajectories were apparent.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Hospitalization; Humans; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; United States

Changes in anemia management practices due to concerns about erythropoiesis-stimulating agent safety and Medicare payment changes may increase patient risk of transfusion. We examined anemia management trends in hemodialysis patients and risk of red blood cell (RBC) transfusion according to dialysis facility-level hemoglobin concentration.. Retrospective follow-up study; 6-month study period (January to June), 3-month exposure/follow-up.. For each year in 2007-2011, annual cohorts of point-prevalent Medicare primary payer patients receiving hemodialysis on January 1 with one or more hemoglobin measurements during the study period. Annual cohorts averaged 170,000 patients, with 130,000 patients and 3,100 facilities for the risk analysis.. Percentage of facility patient-months with hemoglobin level<10 g/dL.. Patient-level RBC transfusion rates.. Monthly epoetin alfa and intravenous iron doses, mean hemoglobin levels, and RBC transfusion rates; percentage of facility patient-months with hemoglobin levels<10 g/dL (exposure) and patient-level RBC transfusion rates (follow-up).. Percentages of patients with hemoglobin levels<10 g/dL increased every year from 2007 (6%) to 2011 (~11%). Epoetin alfa doses, iron doses, and transfusion rates remained relatively stable through 2010 and changed in 2011. Median monthly epoetin alfa and iron doses decreased 25% and 43.8%, respectively, and monthly transfusion rates increased from 2.8% to 3.2% in 2011, a 14.3% increase. Patients in facilities with the highest prevalence of hemoglobin levels<10 g/dL over 3 months were at ~30% elevated risk of receiving RBC transfusions within the next 3 months (relative risk, 1.28; 95% CI, 1.22-1.34).. Possibly incomplete claims data; smaller units excluded; hemoglobin levels reported monthly for patients receiving epoetin alfa; transfusions usually not administered in dialysis units.. Dialysis facility treatment practices, as assessed by percentage of patient-months with hemoglobin levels<10 g/dL over 3 months, were associated significantly with risk of transfusions in the next 3 months for all patients in the facility, regardless of patient case-mix.

Topics: Aged; Anemia; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Insurance Coverage; Kidney Failure, Chronic; Male; Medicare; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk Assessment; United States

Erythropoiesis-stimulating agents (ESAs) are standard therapy for chronic kidney disease (CKD) patients with renal anemia. However, few studies have compared the effects of different ESAs on anemia in identical pre-dialysis CKD patients.. Seventy-nine patients who switched from epoetin beta to darbepoetin alfa (Group 1), and 82 patients who switched from darbepoetin alfa to epoetin beta pegol (Group 2) were enrolled in this study. Clinical and laboratory parameters were assessed for 6 months before and after switching ESAs. The prevalence of adverse events, the dose conversion ratio of ESAs, and the frequency of ESA administration were also analyzed.. Analysis of variance showed that switching ESAs did not significantly change hemoglobin levels for the study duration in both groups (mean hemoglobin 10.3-10.5 g/dL in Group 1 and 10.4-10.7 g/dL in Group 2). Estimated glomerular filtration rate, blood pressure, transferrin saturation, ferritin, and albumin remained constant in both groups. The prevalence of adverse effects was quite low (0-3.8 %) during both 6-month study periods. The mean dose conversion ratio for epoetin beta:darbepoetin alfa was 163.7 units:1 μg and for darbepoetin alfa:epoetin beta pegol was 1.08 μg:1 μg. The intervals of ESA administration significantly differed (epoetin beta pegol > darbepoetin alfa > epoetin beta).. Epoetin beta, darbepoetin alfa, and epoetin beta pegol are effective and well-tolerated agents for managing anemia in Japanese pre-dialysis CKD patients. The intervals of ESA administration to maintain a patient's target hemoglobin were longer in the order of epoetin beta pegol > darbepoetin alfa > epoetin beta.

Topics: Aged; Aged, 80 and over; Anemia; Cohort Studies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Japan; Male; Middle Aged; Recombinant Proteins; Renal Insufficiency, Chronic

We investigated the role of erythropoietin (EPO) in reducing anemia and preventing the development of psychological distress in patients treated with chemotherapy.. This prospective observational study enrolled 591 adult patients receiving EPO at a dose of 30,000 IU administered once weekly for chemotherapy-induced anemia (mean baseline hemoglobin [Hb] level was 9.55 g/dl) over a 12-month period.. The majority of patients (371 [71%] patients) achieved a Hb increase >2 g/dl after 4 weeks of treatment. Interestingly, the nonresponder group had a statistically significant deterioration of their psychological conditions as indicated by psychological distress score (p = 0.01). However, within the group of responders to EPO, the Psychological Distress Inventory score remained unchanged. In the present study, severe side effects associated with EPO were not recorded.. Hb increase, induced by EPO, ameliorates the psychological conditions of cancer patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Stress, Psychological; Treatment Outcome

Few data have been reported on anemia management practices in hospital-based dialysis centers (HBDCs), which are uniquely different from other freestanding dialysis centers. Examining data from HBDCs would help determine if HBDCs and the general US dialysis population have similar trends related to how anemia is managed in dialysis patients.. Given recent changes in the prescribing information of erythropoiesis-stimulating agents (ESAs) and in end-stage renal disease-related health policy and reimbursement, this study describes trends in anemia management practices in HBDCs from January 2010 through March 2013.. Electronic medical records of 5404 adult hemodialysis patients in 50 US-based HBDCs were analyzed retrospectively. Patients included in the study cohort were aged ≥18 years and had at least 1 hemoglobin (Hb) measurement and 1 dose of an ESA between January 2010 and March 2013. End points included Hb concentration, darbepoetin alfa dosing, epoetin alfa dosing, and iron biomarkers (transferrin saturation and ferritin) and dosing.. From 2010 to 2013, mean monthly Hb levels declined from 11.4 to 10.7 g/dL; the percentage of patients with mean monthly Hb levels <10 g/dL increased from 11.3% to 24.4%; and the percentage of patients with mean monthly Hb levels >12 g/dL declined from 30.1% to 11.2%. The median darbepoetin alfa cumulative 4-week dose also declined 38.8%, and the weekly epoetin alfa dose declined 24%. From January 2010 to March 2013, the percentage of patients with transferrin saturation >30% increased from 35.8% to 43.6%, the percentage of patients with ferritin levels >500 ng/mL increased from 62.0% to 77.9%, the percentage of patients with ferritin levels ≥800 ng/mL increased from 28.9% to 47.3%, and the median cumulative 4-week intravenous iron dose increased 50%.. These study results support growing evidence that meaningful changes have occurred over the last 3 years in how anemia is clinically managed in US hemodialysis patients. Study limitations include that changes in patient clinical/demographic characteristics over time were not controlled for and that study findings may not be applicable to HBDCs that have different patient populations and/or do not use an electronic medical record system. Continuing to evaluate anemia management practices in HBDCs would provide additional information on the risks and benefits of anemia care. Consistent with national data, the findings from this study indicate that from 2010 to 2013, HBDCs modified anemia management practices for dialysis patients, as evidenced by reductions in mean monthly Hb levels and ESA dosing and by increases in iron biomarkers and dosing.

Topics: Adolescent; Adult; Aged; Anemia; Cohort Studies; Darbepoetin alfa; Disease Management; Epoetin Alfa; Female; Hematinics; Hemoglobins; Hospitals; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Young Adult

Anemia is common in patients with advanced chronic kidney disease. Whereas the treatment of anemia in patients with end-stage renal disease (ESRD) has attracted considerable attention, relatively little is known about patterns and trends in the anemia care received by patients before they start maintenance dialysis or undergo preemptive kidney transplantation.. To determine the trends in anemia treatment received by Medicare beneficiaries approaching ESRD.. Closed cohort study in the United States using national ESRD registry data (US Renal Data System) of patients 67 years or older who initiated maintenance dialysis or underwent preemptive kidney transplantation between 1995 and 2010. All eligible patients had uninterrupted Medicare (A+B) coverage for at least 2 years before ESRD.. Time, defined as calendar year of incident ESRD.. Use of erythropoiesis-stimulating agents (ESA), intravenous iron supplements, and blood transfusions in the 2 years prior to ESRD; hemoglobin concentration at the time of ESRD. We used multivariable modified Poisson regression to estimate utilization prevalence ratios (PRs).. Records of 466,803 patients were analyzed. The proportion of patients with incident ESRD receiving any ESA in the 2 years before increased from 3.2% in 1995 to a peak of 40.8% in 2007; thereafter, ESA use decreased modestly to 35.0% in 2010 (compared with 1995; PR, 9.85 [95% CI, 9.04-10.74]). Among patients who received an ESA, median time from first recorded ESA use to ESRD increased from 120 days in 1995 to 337 days in 2010. Intravenous iron administration increased from 1.2% (1995) to 12.3% (2010; PR, 9.20 [95% CI, 7.97-10.61]). The proportion of patients receiving any blood transfusions increased monotonically from 20.6% (1995) to 40.3% (2010; PR, 1.88 [95% CI, 1.82-1.95]). Mean hemoglobin concentrations were 9.5 g/dL in 1995, increased to a peak of 10.3 g/dL in 2006, and then decreased moderately to 9.9 g/dL in 2010.. Between 1995 and 2010, older adults approaching ESRD were increasingly more likely to be treated with ESAs and to receive intravenous iron supplementation, but also more likely to receive blood transfusions.

Topics: Aged; Aged, 80 and over; Anemia; Blood Transfusion; Cohort Studies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobin A; Humans; Incidence; Iron; Kidney Failure, Chronic; Medicare; Practice Patterns, Physicians'; Recombinant Proteins; Registries; Renal Insufficiency, Chronic; United States

Myelodysplastic syndromes (MDS) are common in elderly patients. Recombinant human erythro-poietin (rHuEPO) has been widely used to treat anemia in lower risk MDS patients, but few data are known about rHuEPO treatment in the very elderly patient group. In order to investigate the role of rHuEPO treatment in terms of response, overall survival (OS), and toxicity in a very elderly MDS patient group, 93 MDS patients treated with rHuEPO when aged ≥80 years were selected among MDS cases enrolled in a retrospective multicenter study by the cooperative group Gruppo Romano Mielodisplasie (GROM) from Jan 2002 to Dec 2010. At baseline, median age was 82.7 (range 80-99.1) with a median hemoglobin (Hb) level of 9 g/dl (range 6-10.8). The initial dose of rHuEPO was standard (epoetin alpha 40,000 IU/week or epoetin beta 30,000 IU/week) in 59 (63.4 %) patients or high in 34 (36.6 %) (epoetin alpha 80,000 IU/week) patients. We observed an erythroid response (ER) in 59 (63.4 %) patients. No thrombotic event was reported. Independent predictive factors for ER were low transfusion requirement before treatment (p = 0.004), ferritin <200 ng/ml (p = 0.017), Hb >8 g/dl (p = 0.034), and a high-dose rHuEPO treatment (p = 0.032). Median OS from rHuEPO start was 49.3 months (95 % CI 27.5-68.4) in responders versus 30.6 months (95 % CI 7.3-53.8) in resistant patients (p = 0.185). In conclusion, rHuEPO treatment is safe and effective also in the very elderly MDS patients. However, further larger studies are warranted to evaluate if EPO treatment could be worthwhile in terms of quality of life and cost-efficacy in very old patients.

Topics: Age Factors; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Drug Evaluation; Epoetin Alfa; Erythropoietin; Female; Ferritins; Gastrointestinal Diseases; Hematocrit; Humans; Hypertension; Kaplan-Meier Estimate; Male; Multicenter Studies as Topic; Myelodysplastic Syndromes; Prognosis; Proportional Hazards Models; Recombinant Proteins; Retrospective Studies; Thrombosis

The myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders characterized by bone marrow failure and a risk of progression to acute myeloid leukemia (AML). Anemia affects the course of disease, quality of life (QOL), and cognitive function of MDS patients. Erythroid-stimulating agents (ESAs) are effective; however, not all patients respond to ESAs. To evaluate the effectiveness of a biosimilar epoetin α (Binocrit) for the treatment of anemia in low-/intermediate-1 risk MDS patients and to evaluate the impact of ESAs on QOL and on cognitive function, 24 consecutive patients aged over 65 years were treated with Binocrit at 40,000 IU once a week for 12 weeks and were followed for at least 3 months. Responsive patients continued with 40,000 IU once a week for a further 12 weeks. Changes in QOL were assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An), while cognitive assessment was carried out by mini-mental state examination (MMSE). All patients completed 12 weeks of therapy. Sixteen patients (66.67 %) achieved an erythroid response (ER), 15 patients (62.5 %) became transfusion independent and remained free from transfusion requirement for at least 3 months, while two patients had reduction in transfusion requirement of at least four RBC transfusions/8 weeks compared with the pretreatment transfusion requirement. Seven patients were nonresponders (29.1 %), of whom four patients were low risk and three intermediate-I risk. Seven transfusion-independent patients were low risk, and eight were intermediate-1 risk. Median hemoglobin (Hb) values were significantly higher after treatment in responders (p < 0.001). ER was maintained after 24 weeks. Statistically significant positive correlations between improvement in Hb and variations in patients' mini-mental (Spearman's Rho = 0.54, p < 0.01) and FACT-An scores (Spearman's Rho = 0.59, p < 0.003) were demonstrated. This preliminary study shows that Binocrit is promising for the treatment of anemia of MDS patients. ER positively correlates with improvements in patients' cognitive status and positive changes in QOL.

Topics: Aged; Aged, 80 and over; Anemia; Biosimilar Pharmaceuticals; Brain; Epoetin Alfa; Erythropoietin; Female; Humans; Leukemia, Myeloid, Acute; Male; Myelodysplastic Syndromes; Quality of Life; Recombinant Proteins; Retrospective Studies; Risk

The effect of recombinant human erythropoietin (rHuEPO) treatment on the progression of chronic kidney disease (CKD) has not been fully evaluated in Japan. We therefore retrospectively evaluated this in a sub-cohort of a prospective multicenter study to investigate optimal hemoglobin (Hb) level of CKD patients on hemodialysis (HD) treated with rHuEPO; Japan Erythropoietin Treatment Study for Target Hb and Survival (JET study). Effect of rHuEPO treatment during predialysis period to delay initiation of HD was retrospectively assessed in 2434 patients from the JET study comparing groups with and without rHuEPO treatment. The assessment was done by Cox proportional hazards regression analysis and inverse probability-weighted (IPW) analysis to adjust for time-dependent confounders. The weights used in the IPW analysis were calculated using a logistic model that included baseline confounders and time-dependent variables. During the predialysis period, 71.7% (1746 patients) were treated with rHuEPO (mean Hb level of 8.7 g/dL at initiation of rHuEPO treatment). Covariates significantly associated with initiation of rHuEPO treatment were Hb level, serum creatinine level, age, diabetes, cardiac insufficiency, and hypertension. The adjusted hazard ratio for time until HD initiation under rHuEPO treatment was 0.272 (95% CI, 0.223-0.331; P < 0.001) in the Cox analysis and 0.63 (95% CI, 0.53-0.76; P < 0.0001) in the IPW analysis. This retrospective study suggests that rHuEPO treatment during the predialysis period has preventive effects on the progression of CKD although further prospective investigation on the efficacy is needed.

Topics: Aged; Aged, 80 and over; Anemia; Cohort Studies; Disease Progression; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Japan; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

Recovery from blood loss requires a greatly enhanced supply of iron to support expanded erythropoiesis. After hemorrhage, suppression of the iron-regulatory hormone hepcidin allows increased iron absorption and mobilization from stores. We identified a new hormone, erythroferrone (ERFE), that mediates hepcidin suppression during stress erythropoiesis. ERFE is produced by erythroblasts in response to erythropoietin. ERFE-deficient mice fail to suppress hepcidin rapidly after hemorrhage and exhibit a delay in recovery from blood loss. ERFE expression is greatly increased in Hbb(th3/+) mice with thalassemia intermedia, where it contributes to the suppression of hepcidin and the systemic iron overload characteristic of this disease.

Topics: Anemia; Animals; beta-Thalassemia; Blotting, Western; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Epoetin Alfa; Erythropoiesis; Erythropoietin; Gene Expression Profiling; Hemoglobins; Hemorrhage; Hepcidins; Hormones; Iron; Iron Overload; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Sequence Data; Real-Time Polymerase Chain Reaction; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Peginesatide, a long-acting erythropoiesis-stimulating agent, was recalled in February 2013 following reports of serious and sometimes fatal hypersensitivity reactions in dialysis patients who received a first dose. We assessed the relative risks of mortality and morbidity in peginesatide-treated and matched epoetin alfa-treated patients.. From standardized extracts of paid Medicare claims in 2012 and 2013, we identified dialysis patients treated with peginesatide or epoetin between 1 July 2012 and 28 February 2013. For each peginesatide-treated patient, we identified with propensity score matching two epoetin-treated control patients. Patients were followed for up to 2 days after the first peginesatide dose or the referent epoetin dose for death or hospitalization as a result of cardiovascular morbidity or symptoms (composite event), all-cause hospitalization, and emergency room care.. We identified 15 633 peginesatide-treated patients and 31 266 matched epoetin-treated controls. On the day of dose administration, 19 composite events occurred with peginesatide (incidence, 0.12%) and 14 with epoetin (0.04%); the hazard ratio was 2.7 (95% confidence interval, 1.4-5.4). With follow-up for 1 and 2 subsequent days, hazard ratios were 1.6 (1.0-2.4) and 1.5 (1.1-2.0), respectively. Corresponding hazard ratios were larger among hemodialysis patients with neither intravenous antibiotic nor intravenous iron exposure on the day of dose administration. Hazard ratios for all-cause hospitalization and emergency room care exceeded 1 on and after the day of dose administration.. Relative to administration of epoetin alfa, first administration of peginesatide in dialysis patients was acutely associated with higher risk of death or hospitalization as a result of cardiovascular morbidity or symptoms.

Topics: Anemia; Clinical Trials as Topic; Cohort Studies; Databases, Factual; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Peptides; Recombinant Proteins; Renal Dialysis

Anemia management clinics have demonstrated favorable impacts on clinical and economic outcomes and patient satisfaction. Clinical pharmacists are uniquely qualified to manage complex drug therapies requiring intensive monitoring. The complexity, risks associated with inappropriate treatment, and high cost of erythropoietin-stimulating agents (ESAs) make patients on these medications excellent candidates for clinical pharmacist-based management. Integrating ESA management into a clinical pharmacist-managed service has the potential to improve anemia management not only by improving patient outcomes and patient safety, but also by decreasing medication costs.. To (a) assess adherence to monitoring guidelines, efficacy, and safety outcomes and (b) quantify medication utilization expenditures among patients using ESA therapy managed by a clinical pharmacy service compared with usual care.. This is a retrospective longitudinal cohort study of patients with anemia caused by chronic kidney disease who were on ESA treatment for at least 6 months between January 2008 and December 2010. Adherence to monitoring guidelines, efficacy, safety, and drug utilization outcomes were compared between the 2 groups.. A total of 101 patients were included in the study. Of that number, 31 were managed by the pharmacist-managed anemia service, and 70 were in the usual care group. The pharmacist-managed patients had improved adherence to guidelines for hemoglobin monitoring (32.3% vs. 14.3%, P = 0.049) and iron monitoring (61.3% vs. 30.0%, P = 0.005) compared with similar patients receiving usual care. Time to achievement of hemoglobin target was 28 days in the pharmacist-managed group compared with 41 days in the usual care group (P = 0.135), while the proportion of patients achieving target hemoglobin was 96.8% compared with 95.7%, respectively (P = 0.654). Patients in the pharmacist-managed group used less epoetin alfa during the 6-month period, leading to an annualized savings of $1,288 per patient in drug expenditures. . A clinical pharmacist-managed anemia service resulted in improved adherence to national monitoring guidelines, equivalent quality and safety outcomes, and lower medication utilization compared with usual care. 

Topics: Aged; Aged, 80 and over; Anemia; Cohort Studies; Drug Monitoring; Epoetin Alfa; Erythropoietin; Female; Guideline Adherence; Hematinics; Humans; Longitudinal Studies; Male; Middle Aged; Pharmacists; Pharmacy Service, Hospital; Practice Guidelines as Topic; Professional Role; Recombinant Proteins; Renal Insufficiency, Chronic; Retrospective Studies

We simulated the budget impact of biosimilar erythropoiesis-stimulating agent (ESA) in EU G5 countries.. Three models were built to estimate the number of patients who could be provided with antineoplastic therapy with rituximab, bevacizumab or trastuzumab from cost savings of biosimilar erythropoietin use in a hypothetical panel of 100,000 patients. The associated number of patients needed to convert to biosimilar ESA to provide such treatments was also calculated.. Under fixed dosing, the savings from 100% conversion were €110,592,159, translating into an additional 9770 rituximab, 3912 bevacizumab, or 3713 trastuzumab treatments. Under weight-based dosing, the savings from 100% conversion were €146,170,333, corresponding to an additional 12,913 rituximab, 5171 bevacizumab or 4908 trastuzumab treatments. The number of patients needed to convert ranged from four to 51.. Using biosimilar ESA for supportive cancer care yields significant savings and increases accessibility to primary antineoplastic therapy in a budget neutral way.

Topics: Anemia; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Bevacizumab; Biosimilar Pharmaceuticals; Drug Costs; Epoetin Alfa; Erythropoietin; European Union; Hematinics; Humans; Models, Economic; Neoplasms; Recombinant Proteins; Rituximab; Trastuzumab

Hepcidin may play a critical role in the response of patients with anemia to iron and erythropoiesis-stimulating agent therapy. To evaluate the factors affecting serum hepcidin levels and their relation to other indexes of anemia, iron metabolism and inflammation, as well as the dose of erythropoietin, we studied 80 maintenance hemodialysis (MHD) patients treated with recombinant human erythropoietin and their serum hepcidin levels were specifically measured by using a competitive enzyme-linked immunosorbent assay. In linear regression analysis, ferritin was found to be a significant predictor of hepcidin levels in all the study patients. In the absence of apparent inflammation, serum hepcidin levels correlated exclusively with ferritin levels in MHD patients, and it was also an independent marker of inflammation as highly sensitive C-reactive protein.

Topics: Adult; Aged; Anemia; Biomarkers; C-Reactive Protein; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hepcidins; Homeostasis; Humans; Inflammation Mediators; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome

Persistent or "de novo" anemia (plasma hemoglobin<11 g/dL) may complicate the graft outcome in a significant number of renal transplant recipients. We describe a single-center experience with epoetin-zeta (EPO-Z), the biosimilar form for epoetin-alfa.. Twenty patients were included in the study, 10 in treatment with different erythropoiesis-stimulating agents (ESA) and shifted to EPO-Z (shift group) and 10 who started EPO-Z treatment for anemia (naive group). All the patients had stable renal function and normal values of main inflammation markers and were prospectively followed up for 12 months. Iron supplements were administered during the study, as needed.. In the shift group, mean plasma hemoglobin levels>11 g/dL were maintained for the entire 1-year follow-up period, with average EPO-Z doses 3.4% higher than the corresponding doses of previous ESA; in the naive group, the target value was reached between the first and third months and remained stable throughout the study. Mean corpuscular volume did not vary in either group. No change was observed in glomerular filtration rate, nor in proteinuria or in main laboratory data. No drug-related side effect was reported.. EPO-Z may be considered a valid alternative to different ESAs in renal transplant recipients, with an interesting pharmaco-economic profile, considering its lower cost.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Transplantation; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Transplant Recipients

Bone marrow is a key element in the diagnosis of disorders of erythropoiesis, including anemia, and a potential target in their treatment. However, because efficient delivery of diagnostic and therapeutic agents to bone marrow is difficult, such delivery is achieved by administering drugs in large quantities that often have adverse effects. Here, we achieved selective delivery of recombinant human erythropoietin (rHuEPO) to bone marrow, via its encapsulation in liposomes with l-glutamic acid, N-(3-carboxy-1-oxopropyl)-, 1,5-dihexadecyl ester (SA) (liposome-EPO). The result, in a rabbit model of renal anemia, was a beneficial effect on hematopoiesis, better than with rHuEPO alone. Also, we determined that liposome-EPO delivery to bone marrow depended on specific uptake by bone marrow macrophages because of the presence of SA. These results indicate both that liposome-EPO is a new, promising erythropoietin-stimulating agent and that liposomes with SA have potential for diagnostic and therapeutic applications in diseases originating from bone marrow.

Topics: Anemia; Animals; Bone Marrow; Cells, Cultured; Drug Carriers; Drug Delivery Systems; Epoetin Alfa; Erythropoiesis; Erythropoietin; Flow Cytometry; Humans; Kidney Diseases; Liposomes; Macrophages; Male; Rabbits; Recombinant Proteins

Epoetin therapy used to treat anemia among ESRD patients has cost Medicare ∼$40 billion. Since January 2011, epoetin has been reimbursed via a new bundled prospective payment system (PPS). Our aim was to determine changes in epoetin dosing and hematocrit levels in response to PPS by different types of dialysis providers.. Data from the USRDS were used to identify 187,591 and 206,163 Medicare-eligible ESRD patients receiving hemodialysis during January 2010 (pre-PPS) and December 2011 (post-PPS). Standardized weekly mean epoetin dose administered pre- and post-PPS and adjustment in dose (titration) based on previous hematocrit level in each facility was disaggregated by profit status, chain membership and size.. Major declines in epoetin use, dosing and achieved hematocrit levels were observed after PPS. Among the three largest dialysis chains, the decline in standardized epoetin dose was 29% at Fresenius, 47% at DaVita, and 52% at DCI. The standardized weekly epoetin dose among profit and nonprofit facilities declined by 38 and 42%, respectively. Changes in titration patterns suggest that a new hematocrit target of 30-33% was in place after PPS, replacing the erstwhile 33-36% hematocrit target used before PPS.. Historically, important differences in anemia management were evident by dialysis organizational status. However, the confluence of financial incentives bundling epoetin payments and mounting scientific evidence linking higher hematocrit targets and higher epoetin doses to adverse outcomes have culminated in lower access to epoetin and lower doses across all dialysis providers in the first year after PPS.

Topics: Ambulatory Care Facilities; Anemia; Drug Therapy; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Humans; Kidney Failure, Chronic; Medicare; Ownership; Prospective Payment System; Recombinant Proteins; Renal Dialysis; United States

Antibody-mediated pure red cell aplasia (PRCA) is a rare complication of erythropoietin (EPO) therapy. Identification and demonstration of functional activity of EPO antibodies required to diagnose this condition is difficult and only performed in selected laboratories worldwide. In this article we report a recent cluster of three cases of antibody-mediated PRCA over a 16-month period in a single center associated with EPREX use. We also describe the use of a simple low-cost inhibitor assay that can be used to screen for PRCA in local laboratories.

Topics: Aged; Aged, 80 and over; Anemia; Antibodies, Neutralizing; Biomarkers; Calibration; Epoetin Alfa; Erythropoietin; Humans; Male; Predictive Value of Tests; Recombinant Proteins; Red-Cell Aplasia, Pure; Reference Standards; Serologic Tests

The aim was to compare the clinical efficacy of recombinant human erythropoietin (rHuEPO) and darbepoetin alpha (DA) in the treatment of anemia in children with chronic kidney disease (CKD).. Thirty-four (13 female, 21 male) CKD patients were enrolled in the study. Mean age was 11.42 ± 4.05 years. Nine patients were on hemodialysis, 18 were on peritoneal dialysis and seven patients were in CKD stage 4.. Seventeen patients received rHuEPO and the remaining 17 patients received DA. Hemoglobin (Hb) was not significantly different between the two groups during monthly follow up and at the end of 6 months (P > 0.05), but there was a significant increase within each group at the end of 6 months (P = 0.01 for rHuEPO; P = 0.02 for DA). Hb was not different between the patients on and not on dialysis in both groups at the end of the study (P > 0.05). The efficacy of the s.c. and i.v. routes was similar within each group (P > 0.05). Systolic hypertension was observed in only one patient in the DA group, no other adverse effect was observed in either groups.. DA is a reasonable alternative to rHuEPO in the treatment of anemia in pediatric CKD patients, due to its clinical efficacy, convenience of use, patient compliance and tolerability.

Topics: Adolescent; Anemia; Child; Child, Preschool; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobinometry; Humans; Kidney Failure, Chronic; Male; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis; Retrospective Studies

Topics: Anemia; Blood Transfusion; Centers for Medicare and Medicaid Services, U.S.; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Practice Guidelines as Topic; Precision Medicine; Quality of Life; Recombinant Proteins; Renal Dialysis; United States; United States Food and Drug Administration

A population pharmacokinetics/pharmacodynamic (PK/PD) model was developed to describe changes in erythropoiesis as a function of plasma erythropoietin (EPO) concentration over the first 30 days of life in preterm infants who developed severe anemia requiring red blood cell (RBC) transfusion. Several covariates were tested as possible factors influencing the responsiveness to EPO. Discarded blood samples in 27 ventilated preterm infants born at 24-29 wk of gestation were used to construct plasma EPO, hemoglobin (Hb), and RBC concentration-time profiles. The amount of Hb removed for laboratory testing and that transfused throughout the study period were recorded. A population PK/PD model accounting for the dynamic Hb changes experienced by these infants was simultaneously fitted to plasma EPO, Hb, and RBC concentrations. A covariate analysis suggested that the erythropoietic efficacy of EPO is increased for preterm infants at later gestational ages. The PD analysis showed a sevenfold difference in maximum Hb production rate dependent on gestational age and indicated that preterm infants, when stimulated by EPO, have the capacity to produce additional Hb that may result in a decrease in RBC transfusions. The present model has utility in clinical trial simulations investigating the treatment potential of erythropoietic stimulating agents in the treatment of anemia of prematurity.

Topics: Adult; Algorithms; Anemia; Blood Volume; Data Interpretation, Statistical; Epoetin Alfa; Erythrocyte Aging; Erythropoiesis; Erythropoietin; Female; Gestational Age; Hemoglobins; Humans; Infant, Newborn; Infant, Premature; Models, Statistical; Phlebotomy; Plasma Substitutes; Population; Pregnancy; Recombinant Proteins

Resistance to erythropoietin (EPO) treatment has been associated with inflammation and malnutrition in hemodialysis (HD) patients. Depression has also been associated with both inflammation and malnutrition; however, the specific relationship between depressive symptoms and EPO resistance is not known. In the current study, the relationship between depressive symptoms and EPO resistance as evaluated by erythropoiesis stimulating agent (ESA) hyporesponsiveness index (EHRI) was analyzed. 
. Study participants had their medical history taken and underwent physical examination; dialysis adequacy calculation, biochemical analysis and evaluation of depressive symptoms by Beck Depression Inventory (BDI) were performed. EHRI was calculated as the weekly dose of EPO divided by per kilogram of body weight divided by the hemoglobin level.
. The mean BDI score of the patients was 10.99 ± 3.94. Pearson correlation analysis revealed that the logarithmically converted EHRI score was correlated with albumin (r = -0.270, p = 0.011), hs-CRP (r = 0.383, P<0.0001), hemoglobin (r = -0.617, p<0.0001), intact PTH (r = 0.215, p = 0.043) and logarithmically converted BDI (r = 0.299, p = 0.004). The stepwise linear regression analysis revealed that being female (p = 0.012), presence of diabetes mellitus (p = 0.119), hs-CRP (p = 0.009) and BDI score (p = 0.037) were independently related with logarithmically converted EHRI (as a dependent variable).
. Depressive symptoms were independently related with EHRI in HD patients. Studies are needed to highlight underlying mechanisms between depression and EHRI.

Topics: Adult; Aged; Anemia; Biomarkers; Cross-Sectional Studies; Depression; Drug Resistance; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Iron; Kidney Diseases; Linear Models; Male; Middle Aged; Psychiatric Status Rating Scales; Recombinant Proteins; Renal Dialysis; Risk Factors; Time Factors; Treatment Outcome

The erythropoiesis-stimulating agents (ESAs), darbepoetin alfa (DA), and epoetin alfa (EA) differ with respect to dosing schedule in chemotherapy-induced anemia. DA can be administered less frequently than EA, which may increase synchronicity between chemotherapy and ESA schedules. This study compared DA and EA with respect to frequency of synchronization and frequencies of total and ESA healthcare visits in current clinical practice.. A retrospective analysis of ESA utilization during ESA episodes of care was conducted on all cancer patients identified in the SDI health oncology electronic medical records database who underwent chemotherapy and received ESA therapy from July 1, 2007 to March 31, 2010 (n = 6522 DA, n = 3,439 EA).. The frequency of synchronization (chemotherapy and ESA therapy on the same day) was higher with DA (67 %) than EA (58 %) (p < 0.001). The odds that an ESA administration was synchronized with chemotherapy were higher with DA compared with EA (odds ratio = 1.46, 95 % CI: 1.37, 1.54). Compared with EA, DA patients had 2.3 fewer visits with an ESA administration (p < 0.001) and 3.0 fewer total visits (p < 0.001).. Compared with patients receiving EA, DA patients were more likely to have an ESA administration on the same healthcare visit as chemotherapy and had fewer visits for any cause or for ESA administration. These results suggest that through greater synchronization of ESA and chemotherapy administrations, DA may reduce patient and practice burden and healthcare utilization.

Topics: Adolescent; Adult; Aged; Ambulatory Care Facilities; Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Appointments and Schedules; Darbepoetin alfa; Databases, Factual; Drug Administration Schedule; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies; Young Adult

In a setting with two concurrent treatments, inverse-probability-of-treatment weights can be used to estimate the joint treatment effects or the marginal effect of one treatment while taking the other to be a confounder. We explore these two approaches in a study of intravenous iron use in hemodialysis patients treated concurrently with epoetin alfa (EPO).. We linked US Renal Data System data with electronic health records (2004-2008) from a large dialysis provider. Using a retrospective cohort design with 776,203 records from 117,050 regular hemodialysis patients, we examined a composite outcome: mortality, myocardial infarction, or stroke.. With EPO as a joint treatment, inverse-probability-of-treatment weights were unstable, confidence intervals for treatment effects were wide, covariate balance was unsatisfactory, and the treatment and outcome models were sensitive to omission of the baseline EPO covariate. By handling EPO exposure as a confounder instead of a joint treatment, we derived stable weights and balanced treatment groups on measured covariates.. In settings with concurrent treatments, if only one treatment is of interest, then including the other in the treatment model as a confounder may result in more stable treatment effect estimates. Otherwise, extreme weights may necessitate additional analysis steps.

Topics: Anemia; Confounding Factors, Epidemiologic; Drug Therapy, Combination; Epidemiologic Methods; Epoetin Alfa; Erythropoietin; Ferric Compounds; Hematinics; Humans; Kidney Failure, Chronic; Medicare; Myocardial Infarction; Outcome Assessment, Health Care; Recombinant Proteins; Renal Dialysis; Stroke; Transferrin; United States

Topics: Anemia; Drug Costs; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Nephrology; Recombinant Proteins; Renal Dialysis; United States

Prior longitudinal observational studies have examined the practice patterns and outcomes of anaemia management, including the use of erythropoiesis-stimulating agents (ESAs). Several dimensions of effectiveness remain unaddressed; especially considering the revised ESA label (target Hb levels between 10 and 12 g/dL), the recently published TREAT study, and the European approval of the first ESA biosimilar (HX575). Anecdotal evidence suggests that patient outcomes are influenced by physician-related variables and whether anaemia management is congruent with practice guidelines, but this has not been studied systematically. MONITOR-CKD5 is an international, prospective, observational, pharmacoepidemiological study evaluating the multi-level factors and outcomes of treatment with HX575 for renal anaemia in haemodialysis patients. Driven by a novel, integrated, multi-focal framework for post-approval observational studies, it examines determinants of response at both the patient and the physician level; integrates an advocated statistical methodology here to fore used mainly in the social and behavioural sciences; assesses factors potentially predictive of a poor treatment response; and evaluates the extent to which treatment is congruent with evidence-based guidelines, good practice evidence, and the revised ESA label. This pan-European study will recruit at least 1,000 patients from a minimum of 75 centres, and follow them for up to 24 months following initiation of anaemia management with biosimilar epoetin alfa. MONITOR-CKD5 will not only study the core issues addressed by prior observational studies but also aims to take knowledge discovery a step further by assessing outcomes across varying cohorts of patients, and examining the impact of evidence-based practice on clinical outcomes, differentiating, in the process, between physician-level and patient-level determinants.

Topics: Adult; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Pharmacoepidemiology; Predictive Value of Tests; Prospective Studies; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Anemia in chronic renal failure results from inadequate production of erythropoietin and decrease in its biological activity, and the reduced activity of erythropoietin is caused by the presence of plasma inhibitors of erythropoietin. It is reported that one of the inhibitors of erythropoietin is cyanate, a potential uremic toxin formed spontaneously from increased urea due to decreased renal function, and erythropoietin loses its biological activity due to negatively charged cyanate. The purpose of this study is to investigate the protective effects of amino acids, positively charged amino groups, and albumin binding of several toxins on erythropoietin carbamoylation.. The degree of change in erythropoietin structure by cyanate was measured by the trinitrobenzenesulphonate reaction and Western blotting. The loss of biological activity of erythropoietin caused by cyanate was measured by injecting erythropoietin into rats with chronic renal failure.. The free amino groups in erythropoietin decreased under cyanate treatment in a time- and concentration-dependent manner. In the cyanate treatment group, of the twenty amino acids, phenylalanine, valine, tryptophan, threonine, and lysine prevented the structural modification of erythropoietin, according to Western blot analysis. In addition, of the three proteins, albumin prevented the structural modification of erythropoietin. As for the cyanate with erythropoietin treatment group, only lysine and albumin prevented the loss of biological activity of erythropoietin in the rats.. The results of this study suggest that lysine and albumin may play a protective role against renal anemia by erythropoietin carbamoylation in chronic renal failure.

Topics: Albumins; Amino Acids; Anemia; Animals; Cyanates; Epoetin Alfa; Erythropoietin; Kidney Failure, Chronic; Male; Rats; Rats, Sprague-Dawley; Recombinant Proteins

To examine epoetin alfa (EPO) and darbepoetin alfa (DARB) treatment patterns and erythropoiesis stimulating agent (ESA) costs in patients with cancer receiving chemotherapy (CRC), and to compare the results observed in the pre-matched total study population (TSP) with a propensity score matched population (PSMP).. A medical claims analysis was conducted from 1 January 2004 through 31 July 2009 using the HealthCore Integrated Research Database. Patients were at least 18 years old, newly initiated on EPO or DARB, received ≥ 2 ESA doses, and had ≥ 1 claim for cancer and chemotherapy proximate to ESA treatment. Patients were matched using propensity scores. January 2010 Wholesale Acquisition Cost was used to calculate drug cost. Mean cumulative ESA dose and drug costs were evaluated in the TSP and PSMP.. 4921 EPO and 9173 DARB patients with CRC were identified. In the TSP, mean cumulative ESA doses were EPO: 398,770 units and DARB: 1508 mcg, with similar treatment durations for each. Mean cumulative drug costs were EPO: $6041 and DARB: $7861 (30% higher for DARB). The cumulative dose ratio (EPO units: DARB mcg) was 264:1. The PSMP analysis identified 4831 ESA treated CRC patients in each group. Mean drug costs were EPO: $6055 and DARB: $7863 (30% higher for DARB). The observed dose ratio (EPO units: DARB mcg) was 265:1.. In both analyses, the costs of DARB were higher, even after accounting for baseline differences in the PSMP. Similar trends in dose ratios were also observed in both groups.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Cohort Studies; Darbepoetin alfa; Databases, Factual; Dose-Response Relationship, Drug; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Propensity Score; Recombinant Proteins; Retrospective Studies

To determine whether the use of a nurse-driven protocol in the haemodialysis setting is as safe and effective as traditional physician-driven approaches to anaemia management.. The role of haemodialysis nurses in renal anaemia management has evolved through the implementation of nurse-driven protocols, addressing the trend of exceeding haemoglobin targets and rising costs of erythropoietin-stimulating agents.. Retrospective, non-equivalent case control group design.. The sample was from three haemodialysis units in a control group (n = 64) and three haemodialysis units in a protocol group (n = 43). The protocol group used a nurse-driven renal anaemia management protocol, while the control group used a traditional physician-driven approach to renal anaemia management. All retrospective data were obtained from a provincial renal database. Data were analysed using chi-square tests and t-tests. Patient outcomes examined were haemoglobin levels, transferrin saturation levels, erythropoietin-stimulating agents use and intravenous iron use. Cost comparisons were determined using average use of erythropoietin-stimulating agents and intravenous iron.. Control and protocol groups reached haemoglobin target levels. In the protocol group, 75% reached transferrin saturation target levels in comparison with 25% of the control group. Use and costs for iron was higher in the control group, while use and costs for erythropoietin was higher in the protocol group. The higher usage of erythropoietin-stimulating agents was potentially related to comorbid conditions amongst the protocol group.. A nurse-driven protocol approach to renal anaemia management was as effective as the physician-driven approach in reaching haemoglobin and transferrin saturation levels. Further examination of the use and dosing of erythropoietin-stimulating agents and intravenous iron, their impact on haemoglobin levels related to patient comorbidities and subsequent cost effectiveness of protocols is required.. Using a nurse-driven protocol in practice supports the independent nursing role while contributing to safe patient outcomes.

Topics: Aged; Anemia; Case-Control Studies; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Nurse's Role; Recombinant Proteins; Renal Dialysis; Retrospective Studies

To assess the clinical and economic outcomes among patients with chemotherapy-induced anemia (CIA) treated with United States Food and Drug Administration-approved fixed dosing regimens of erythropoiesis-stimulating agents (ESA).. Data were employed from the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) registry to evaluate CIA patients who were initiated on either epoetin alfa (EPO) 40,000 Units (U) or darbepoetin alfa (DARB) 500 micrograms (mcg) between January 1, 2006 and May 8, 2009. Study measurements included ESA treatment dose and dose ratio, changes in hemoglobin (Hb) levels from baseline, and cumulative ESA costs.. Five hundred forty patients treated in 44 clinical centers were evaluated, of which 420 were initiated on EPO 40,000 U and 120 were initiated on DARB 500 mcg. Both cohorts had similar baseline characteristics, although EPO patients were less likely than DARB patients to have received iron supplementation before ESA initiation (11.4% EPO vs. 20.0% DARB, p = 0.015). The EPO-to-DARB dose ratio based on cumulative ESA dose was 169:1 (U EPO: mcg DARB). EPO patients showed statistically greater Hb improvement compared to DARB patients, and compared to EPO patients, a greater proportion of DARB patients required a blood transfusion (13.9% EPO vs. 22.5% DARB, p = 0.026). Mean cumulative ESA cost was significantly lower for EPO patients than DARB patients ($4,261 EPO vs. $8,643 DARB, p < 0.0001).. These findings reported that patients with CIA achieved more favorable clinical and economic outcomes if initiated with EPO 40,000 U vs. DARB 500 mcg.

Topics: Aged; Anemia; Antineoplastic Agents; Darbepoetin alfa; Dietary Supplements; Dose-Response Relationship, Drug; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Iron; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins; Registries; Treatment Outcome

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins

ESA therapy can increase hemoglobin, decrease blood transfusions, and improve quality of life in patients with chemotherapy induced anemia (CIA). Despite its benefits, ESA therapy increases the risk of venous thromboembolism (VTE) in cancer patients by 50% and can also cause iron restricted erythropoiesis in CIA patients, which may augment the tendency to develop VTE. We postulated that thrombocytosis, a risk factor for VTE in cancer patients, in CIA patients on ESA therapy might be a result of ESA induced iron restricted erythropoiesis. We performed a retrospective analysis of 187 CIA patients who were randomized to receive weekly Epoetin and IV ferric gluconate, oral ferrous sulfate, or no iron for 8 weeks. Nineteen patients experienced 29 VTEs, and patients, whose platelets increased to ≥350,000 cells/uL were three times more likely to experience a VTE (OR 2.9, P = 0.036, logistic regression) with a four times greater incidence of VTE (IRR 4.4, P = 0.001, Poisson regression). Patients treated with IV iron were significantly less likely to develop platelets of ≥350,000 cells/uL (IRR 0.7, P = 0.013, Poisson regression) and had a decreased incidence of VTE. Our study suggests that ESA associated VTE in CIA patients may be, in part, related to the thrombocytosis of ESA induced iron restricted erythropoiesis and may be countered by IV iron.

Topics: Aged; Anemia; Anemia, Iron-Deficiency; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferric Compounds; Ferrous Compounds; Hematinics; Hemoglobins; Humans; Iron; Male; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Thrombocytosis; Thrombophilia; Venous Thromboembolism

Epoetins are one of the three biologics for which biosimilars are available in Italy. So far, there is a lack of Italian national/regional longitudinal data about epoetin use.. The aim of this study was to evaluate the prescribing pattern of epoetins (reference products and biosimilars) in a Local Health Unit (LHU) of Southern Italy in recent years.. A retrospective drug utilization study was conducted during the period 1 January 2010 - 31 May 2011. The data source was the dispensing database of the Messina LHU, which contains anonymized data about dispensed drugs (including epoetins) that are prescribed by specialists to the residents in the catchment area. Indication of use and prescribed dosage of epoetins were derived by the therapeutic plans filled in by specialists and linked to drug dispensing records. Prevalence of epoetin use in the province of Messina (653 810 inhabitants) in 2010 was calculated. Furthermore, frequency analyses by sex, age, indication of use of epoetin users, as well as measurement of volume of use (defined daily dose [DDD]/1000/day) and expenditure of epoetins in 2010 were also performed. Analysis of the switching pattern between different reference products and biosimilar epoetins was performed.. Overall, 4288 patients were treated with epoetins during the study period (mean age  ± SD: 74.2 ± 13.7; females: 52%). Darbepoetin alpha and reference product epoetin alpha accounted overall for 79.8% of epoetin users, while biosimilars of epoetin alpha accounted for 0.9%. Among 1247 epoetin users for whom the therapeutic plan was revised, 1065 (85.4%) were treated because of anemia due to chronic kidney disease and 158 (12.6%) because of chemotherapy-induced anemia. In 2010, prevalence of epoetin use was 5.5 (95% CI 5.3, 5.7) per 1000 inhabitants in the province of Messina. The volume of use and related expenditure for epoetins was 3.58 DDD/1000 inhabitants/day and Euro 5 572 457 (about Euro 8.50 per capita/day) in 2010. Switching between different epoetins was very frequent (21.8% of users) but switching from reference products to biosimilars was very rare.. Epoetins are frequently dispensed to residents in the province of Messina, mainly for the treatment of chronic kidney disease-related anemia, with a relevant impact on the pharmaceutical expenditure covered by the National Health System. Use of biosimilar products is very low in both naïve patients and in those who switch from other reference product epoetins.

Topics: Aged; Anemia; Biosimilar Pharmaceuticals; Darbepoetin alfa; Drug Prescriptions; Drug Utilization; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Italy; Male; Recombinant Proteins; Retrospective Studies

Topics: Anemia; Biotechnology; Commerce; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Patents as Topic; Peptides; Recombinant Proteins; United States

In 2005, the mean weekly dose ratio of epoetin alfa (EA) to darbepoetin alfa (DA) in clinical practice was estimated to be ∼400 to 1. In 2006, a 500-μg dose and new dosing schedule was approved for DA in the United States. In 2007, the warnings and dosing/administration sections were modified for both agents. All of these factors may have changed the way that physicians use EA and DA. Previous studies of the use of erythropoiesis-stimulating agents (ESAs) in patients with anemia concomitant with chemotherapy may thus not reflect current clinical practice.. The goal of this study was to examine the use and costs of ESAs in clinical practice in patients with anemia concomitant with chemotherapy.. Using 2 large US health care claims databases, all adults (aged ≥18 years) were identified who received ESAs in 2008 and had evidence of receipt of chemotherapy ≤42 days before initial ESA receipt (ie, the index date). Episodes of care were defined as beginning on the index date and ending on the date of the last ESA claim that was followed by a ≥42-day gap without any receipt of ESAs, to which was added an assumed duration of clinical benefit (in days) based on the ESA and corresponding dose received. DA- and EA-treated patients were matched using propensity scoring. The mean weekly dose and cost of DA and EA during episodes of care was calculated using all information from relevant claims noted during such episodes. Each database was analyzed separately.. In the first database, 475 patients with DA episodes of care were matched to an equal number of patients with EA episodes; in the second database, there were 424 matched pairs. In the first database, the mean (95% CI) weekly dose was 37,444 U (35,942 U-39,001 U) during EA episodes and 110 μg (108 μg-113 μg) during DA episodes; the mean weekly EA/DA dose ratio was 340 to 1. In the second database, the mean (95% CI) weekly dose was 37,047 U (35,944 U-38,175 U) during EA episodes and 121 μg (117 μg-125 μg) during DA episodes; the mean weekly EA/DA dose ratio was 306 to 1.. The mean weekly EA/DA dose ratio during episodes of ESA care has declined in patients with anemia concomitant with chemotherapy, due at least in part to the availability and use of a new dose/dosing schedule for DA without similar changes for EA.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Utilization Review; Episode of Care; Epoetin Alfa; Erythropoietin; Humans; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Diseases; Product Surveillance, Postmarketing; Recombinant Proteins; Renal Dialysis

Techniques that assess percent reticulocytes (%retics) or hemoglobin (Hb) to detect erythropoiesis-stimulating agents (ESA) use in athletes may be useful in evaluating ESA responsiveness in dialysis patients. However, within-patient variation, appropriate transformation, or the relationship between the blood draw interval length and analyte variation are untested.. In a prospective, single-arm trial, we determined Hb and %retics in 30 hemodialysis patients receiving stable ESA doses. Within-patient results were evaluated for variance homogeneity and normality with and without transformation.. Square-root transformation (sqrt) of %retics produced the most constant variance (lowest r-value for correlation between sqrt|normalized residuals| and fitted values: 0.018 highest P-value 0.739) compared with log transformation (r = -0.198, P < 0.001) or no transformation (r = 0.215, P < 0.001) and showed the least departure from normality (highest P-value: 0.002 vs. < 0.001 vs. < 0.001, respectively). Hb results did not improve with transformation. Within-patient variance in both %retics and Hb increased with interval length between lab draws (P < 0.001).. Initial assessment of anti-doping tool use in dialysis patient anemia management indicates square-root transformation of %retics and adjustment for time between lab draw intervals for both %retics and Hb will be required.

Topics: Anemia; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Iron; Linear Models; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Renal Dialysis; Reticulocyte Count

Topics: Anemia; Chronic Disease; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Diseases; Practice Guidelines as Topic; Quality of Life; Recombinant Proteins; Renal Dialysis; United States

The management of anaemia in chronic kidney disease (CKD) to achieve current guideline goals is difficult and is hindered by multiple factors, including problems with the scheduling and adjustment of dosing of erythropoiesis-stimulating agents (ESAs) and the frequency of required ESA administration to achieve target haemoglobin (Hgb) levels.. The primary objective of this study was to examine whether converting a large cohort of CKD patients receiving epoetin alfa to darbepoetin alfa would decrease the frequency of drug administration while permitting an acceptable management of CKD-related anaemia.. In this retrospective cohort study of practice in a community-based CKD anaemia clinic, we evaluated the effects of conversion of a baseline group of 283 patients from epoetin alfa to darbepoetin alfa with a goal of decreasing the frequency of ESA administration while maintaining Hgb levels within a target range. The study observation period extended for 15 months after the initial conversion. An additional 256 CKD patients were started on darbepoetin alfa during the observation period and the frequency of their injections and the range of their Hgb levels were also monitored.. Following the conversion to darbepoetin alfa, we were able to increase the number of patients on once-monthly injections from 21% to 76% while keeping Hgb levels in the target range and maintaining stable blood pressure control. The mean number of ESA injections/patient/month decreased from 2.1 to 1.3.. In a community-based CKD anaemia clinic, conversion from epoetin alfa to darbepoetin alfa resulted in a decreased frequency of injections needed to maintain Hgb levels within an accepted target range.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Community Health Centers; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Retrospective Studies

A transition in the approach to anemia management in nephrology occurred when randomized trials demonstrated that higher hemoglobin targets do not result in better outcomes and may arguably cause harm. Contradicting the speculative conclusions drawn based on earlier observational data, this has resulted in hypotheses regarding the cause of these seemingly disparate but substantively similar messages. The renal community now must struggle with how to incentivize quality care and maximize patient quality of life while minimizing the real safety signal of which we are now aware.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Insufficiency, Chronic

Topics: Anemia; Epoetin Alfa; Erythropoietin; Germany; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

In May 2009 for financial reasons, the epoetin product used for hemoglobin (Hb) maintenance in our renal dialysis unit was changed from epoetin beta to epoetin alfa. Although widely believed that the dosage requirements are the same, we undertook a retrospective analysis to investigate whether the dosage requirements in chronic renal failure patients were comparable for both preparations. We studied 128 stable end-stage renal failure patients on hemodialysis (three times per week) receiving erythropoietin therapy to maintain their Hb at 11-12.5 g/dL. Patients were excluded if within the study period they developed signs of infection, bleeding, required blood transfusion, were under-dialyzed, or required hospital admission. Regular monthly Hb concentrations and hematocrit (Hct) levels were measured for each patient. The weekly EPO index (defined as weekly epoetin dose/mean monthly Hct) was derived for each patient, before and after regime change. Of the 128 patients in end-stage renal failure, 79 were included in the study. There was no significant difference between the two preparations in terms of Hct level achieved (p = 0.15). However, the median weekly epoetin dose requirement increased from 6733 (range 750-30,000) IU/week to 9000 (250-30,667) IU/week (p < 0.001). EPO index similarly increased from 20,465 (2500-130,846) IU/week/% to 27,073 (729-98,937) IU/week/% (p < 0.001). Our study showed that a higher dose of epoetin alfa was needed to maintain target Hb concentration.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Retrospective Studies

Topics: Anemia; Angioplasty, Balloon, Coronary; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Magnetic Resonance Imaging; Myocardial Infarction; Myocardial Reperfusion; Randomized Controlled Trials as Topic; Recombinant Proteins; Ventricular Remodeling

Frequent dosing and requirements for dose adjustments of erythropoiesis-stimulating agents (ESAs) create significant burdens for healthcare providers and have been associated with hemoglobin (Hb) cycling, hampering maintenance of target Hb levels. We compared the frequency of dose changes in dialysis patients who received methoxy polyethylene glycolepoetin beta; (a continuous erythropoietin receptor activator (C.E.R.A.)) or a shorter-acting ESA.. Data were analyzed from three Phase III maintenance trials, using almost identical protocols, in dialysis patients treated with C.E.R.A. every 2 weeks (q2w) or every 4 weeks (q4w) or a comparator ESA (epoetin or darbepoetin alpha; at their previous dose/administration interval). Dosage was adjusted to maintain Hb ± 1 g/dl of baseline and 10 - 13.5 g/dl during titration (28 weeks) and evaluation (8 weeks), and 11 - 13 g/dl during follow-up (16 weeks).. Data were analyzed from 564 patients treated with C.E.R.A. q2w, 410 with C.E.R.A. q4w and 572 with comparator ESA at their usual dosing interval. Significantly fewer dose changes were needed in patients receiving C.E.R.A. q2w (p < 0.05) or C.E.R.A. q4w (p < 0.001) than in patients treated with comparator ESAs.. This retrospective analysis suggests that C.E.R.A. q4w maintains Hb levels in dialysis patients and requires fewer dose changes compared with other ESAs.

Topics: Anemia; Chronic Disease; Clinical Trials, Phase III as Topic; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins

The four currently available erythropoiesis-stimulating agents (ESAs), the main drugs for correcting anemia in patients with chronic kidney disease (CKD), are epoetin alfa, epoetin beta, darbepoetin alfa, and continuous erythropoietin receptor activator. The last two have much longer half-lives, which means they can be administered less frequently. The expiry of the patents for epoetin alfa and epoetin beta some years ago opened up the way for the production of a number of biosimilars that are now marketed in the European Union. Because biosimilars cannot be identical to their originator, a complex and still-evolving regulatory policy has been generated, but there are still a number of issues concerning international naming, automatic substitution, and safety. All ESAs are effective in correcting renal anemia and increasing hemoglobin levels, but the choice of which to use should also take into account their pharmacokinetics and pharmacodynamics, their administration route, and economic issues. Following the publication of a number of trials indicating no benefit (and even possible harm) when ESAs are used to aim at near-normal hemoglobin levels in CKD patients, the hemoglobin target has become a major subject of discussion. According to the position statement of the Anemia Group of the European Renal Best Practice, it should generally be about 11-12 g/dL; however, a risk-benefit evaluation is warranted in individual patients, and high ESA doses driven by hyporesponsiveness should be avoided.

Topics: Anemia; Chronic Disease; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; European Union; Hematinics; Hemoglobins; Humans; Kidney Diseases; Polyethylene Glycols; Recombinant Proteins

This article describes the method by which the repatriation to the Netherlands of psychiatric patients living abroad is carried out. On the basis of one case, namely that of a psychotic male with low Hb and fear of HIV, it is shown that the repatriation of psychiatric patients can be extremely complex and that a psychiatrist's active involvement in the patient's repatriation can be extremely important.

Topics: Adult; Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Holidays; Humans; Male; Netherlands; Psychotic Disorders; Recombinant Proteins; Senegal; Transportation of Patients

Renal anemia is complication of chronic kidney disease. It is caused by crythropoietin deficency and is associated with adverse outcomes in CKD patients. Renal anemia should be treated with erythropoesis-stimulating agents (ESAs), supplementary iron, adequate dialysis, and if necessary with red blood cells transfusions. The main problem of treatment is how to determine target hemoglobin value and keep it within the constant range. Current guidelines recommend target hemoglobin level 110 - 120 g/l, but optimal value need to be adjusted for every patient individualy keeping in mind primary kidney disease, age, gender and comorbidities. In Department of Dialysis of General Hospital Bjelovar we carried out a retrospective study about treating renal anemia in 67 patients on chronic hemodialysis program during 36 months in a period from 2007. til 2010. We monitored hemoglobin, feritin, saturation of transferin (TSAT), dose of LSE, number of change in dosage and number of transfusion. Mean hemoglobin level was 107.8 g/l, feritin level 196.8 mcg/l, TSAT 24.16%, weekly dose of ESAs 5951.9 IU. in 53.7% patiens dose was changed 11 - 20 times during that period, and 34% of patiens was treated with at least 1 dose of transfusion of red blood cells. We conclude that better iron supplementation and moderately higher doses of FSAs correlate with higher hemoglobin value, and hemoglobin variations is still big problem in renal anemia treatment.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

A number of anaemic cancer patients are not responsive to treatment with recombinant human erythropoietin (rHuEPO). The aim of the present study is to investigate whether serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6 and additional laboratory parameters, together with clinical variables, can predict the clinical outcome of treatment with rHuEPO in anaemic cancer patients.. Thirty-five cancer patients and 25 healthy controls were enrolled in this study. Patients were treated with epoetin alfa at the dose of 150 IU/kg s.c. three times a week for 12 weeks. If the haemoglobin (Hb) level failed to improve at least 2 g/dl above baseline by week 6 of treatment, dose was increased to 300 IU/kg s.c. for the remainder of the treatment period. All patients filled out the Brief Fatigue Inventory (BFI), a questionnaire for the self-evaluation of cancer-related fatigue. Serum samples from patients and control groups were frozen at -80 degrees C and TNF-alpha, IL-1beta and IL-6 were later examined by enzyme-linked immunosorbent assay.. Fatigued cancer patients had significant higher levels of circulating TNF-alpha, IL-1beta and IL-6 than healthy controls. Responders (Rs) to erythropoietin had significant lower medium levels of TNF-alpha and IL-6 than nonresponders (NRs). Fatigued patients with a general BFI score > or =6 presented higher medium level of cytokines than nonfatigued patients (general BFI score <6), but each group responded similarly to treatment with rHuEPO.. High serum levels of TNF-alpha and IL-6 at the baseline are significantly correlated with a negative response to administration with rHuEPO. Thus, pretreatment evaluation of TNF-alpha and IL-6 serum levels can help to select those patients who are most likely to benefit from treatment with rHuEPO. On the contrary, Hb level, red blood cell count, lactate dehydrogenase and BFI score do not predict the outcome of treatment with rHuEPO.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Interleukin-6; Male; Middle Aged; Neoplasms; Recombinant Proteins; Survival Rate; Treatment Outcome; Tumor Necrosis Factor-alpha

Topics: Anemia; Chronic Disease; Darbepoetin alfa; Epoetin Alfa; Erythrocytes; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Diseases; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Anemia; Cardiovascular Diseases; Darbepoetin alfa; Diabetes Mellitus, Type 2; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Recombinant Proteins; Renal Insufficiency, Chronic

Anemia is common in chronic kidney disease (CKD). The CHOIR study found increased risk of a composite cardiovascular outcome when anemia was treated with epoetin-alfa to a target hemoglobin level of 13.5 as compared with 11.3 g/dl. Whether this increase applies to all patient subgroups equally is unclear. We discuss an analysis by Szczech and colleagues of the effects of the higher hemoglobin target in CKD patients with diabetes mellitus or congestive heart failure.

Topics: Anemia; Chronic Disease; Diabetes Mellitus; Epoetin Alfa; Erythropoietin; Heart Failure; Hemoglobins; Humans; Kidney Diseases; Recombinant Proteins

We present a case of a young girl with end-stage renal disease secondary to anti-glomerular basement membrane disease who was receiving maintenance peritoneal dialysis and developed pure red cell aplasia secondary to anti-erythropoietin (EPO) antibodies. This occurred 13 months after the initiation of EPO alfa therapy for anemia. Initially, the patient required intermittent red blood cell transfusions. After immunosuppressive therapy had been initiated with corticosteroids and cyclosporine, the EPO antibody levels decreased precipitously, associated with an increased level of endogenous EPO production. For the following 6 months, the patient maintained adequate (>10 g/dL) hemoglobin levels and did not require red cell transfusions.

Topics: Anemia; Antibodies; Child, Preschool; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure; Renal Dialysis; Time Factors; Treatment Outcome

The erythropoietic response in hemodialysis patients depends on several physiologic factors. Most epidemiologic studies include the effect of these factors by representing them as confounders. This study tested the hypothesis that iron stores, inflammation, dialysis adequacy, nutritional status, and hyperparathyroidism act as nonlinear effect modifiers of the erythropoietic response and quantified the magnitude of those effects over clinically relevant ranges.. The following retrospective data from 209 hemodialysis patients receiving Epoetin alfa (Epo) were collected: monthly: predialysis hemoglobin (Hgb), transferrin saturation, serum albumin, dialysis adequacy (Kt/V); quarterly: predialysis serum ferritin and intact parathyroid hormone over a period of 13 to 69 months. The study analyzed the dynamic relationship between hemoglobin and Epo, considering nonlinear effect modification by ferritin, transferrin saturation, Kt/V, albumin, and parathyroid hormone individually.. Maximum Hgb response to Epo was achieved for serum ferritin between 350 and 500 ng/ml, transferrin saturation greater than 30%, Kt/V greater than 1.4, and albumin greater than 3.8 g/dl. Hgb sensitivity to Epo decreases by about 30% as parathyroid hormone increases from 0 through 1000 pg/ml.. Serum ferritin, transferrin saturation, Kt/V, serum albumin, and intact parathyroid hormone are markers of nonlinear effect modification of the erythropoietic response in hemodialysis patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Biomarkers; Confounding Factors, Epidemiologic; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Hyperparathyroidism; Inflammation; Iron; Kidney Diseases; Likelihood Functions; Logistic Models; Male; Middle Aged; Nonlinear Dynamics; Nutritional Status; Parathyroid Hormone; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Serum Albumin; Time Factors; Transferrin; Treatment Outcome; Young Adult

The health-related quality of life (HRQOL) claims in the current Epoetin alfa label are based on the reanalyses of the exercise and physical function data from the Canadian Erythropoietin Study Group trial. The reanalysis was done to comply with the Food and Drug Administration's requirement of using statistical methods that are currently standard in evaluating clinical trial data. Presented here are HRQOL results associated with anemia. The Canadian Erythropoietin Study Group trial was a multicenter, double blind, randomized, placebo-controlled trial evaluating the effects of Epoetin alfa on HRQOL in anemic hemodialysis patients. A total of 118 patients who were 18-75 years old, on hemodialysis for >3 months, who had a hemoglobin <9.0 g/dL, and did not have coronary artery disease or diabetes mellitus, were randomized to either receive placebo (n=40), or receive intravenous Epoetin alfa to achieve a target hemoglobin of 9.5-11.0 g/dL (n=40) or a target of 11.5-13.0 g/dL (n=38). Patients were followed for 6 months. The two Epoetin alfa-treatment groups were combined for all analyses performed. This post hoc analysis was conducted using an intent-to-treat repeated measures mixed model analysis of variance using Bonferroni's multiplicity correction. The Epoetin alfa-treated group showed a statistically significant improvement in the Kidney Disease Questionnaire symptom of fatigue in comparison with placebo. Additionally, the change in hemoglobin at 2 months was correlated with change in fatigue, energy, shortness of breath, and weakness, but had minimal effect on depression. These analyses confirm previously reported results, which indicate that treating hemodialysis patients with an erythropoiesis-stimulating agent improves HRQOL.

Topics: Adult; Aged; Anemia; Canada; Data Interpretation, Statistical; Epoetin Alfa; Erythropoietin; Fatigue; Female; Health Status; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Documentation; Epoetin Alfa; Erythropoietin; Health Policy; Hematinics; Humans; Neoplasms; Recombinant Proteins; Risk Management; United States; United States Food and Drug Administration

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Palliative Care; Recombinant Proteins; Risk; United States; United States Food and Drug Administration

Topics: Anemia; Diabetes Complications; Endpoint Determination; Epoetin Alfa; Erythropoietin; Heart Failure; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins

Recombinant human erythropoietin (rHuEpo) has revolutionized the management of renal anemia, significantly improving patient quality of life. Great attention has been paid lately on how to optimally use this potent anti-anemic agent. Aiming to overview anemic patient management with Epotin (Julphar's rHuEpo) according to the new guidelines, we included in the study anemic (hemoglobin [Hb]or=18 years who were of iron replete (transeferene saturation (TSAT)>or=20% and serum ferritin>or=100 microg/L) with no evidence of serious inflammation (c-reactive protein (CRP)<30 mg/L) on thrice-weekly hemodialysis. The mean age and dialysis duration of 50.8+/-17 and 3.8+/-2.8 years, respectively, included 88.6% (n=31) de novo patients in the corrective phase with no previous exposure to erythropoietin. Safety-efficacy parameters showed insignificant changes throughout the 4-month study period, including iron profile that was maintained according to Kidney Disease Outcome Quality Initiative guidelines. Efficacy parameters revealed a significant increase (P<.0001) of Hb levels from a baseline of 8.5+/-1.0 to 11.1+/-1.1. Targeting an absolute increase of 2.5 g/dL in Hb throughout 3 months of the study period resulted in a 90.3% success rate. There were no dropouts due to intolerance, whereas all the recorded adverse events were classified as unrelated to the test product. In conclusion, Epotin was clinically effective to correct and maintain Hb levels in ESKD anemic patients on maintenance hemodialysis within the current recommended range and with a satisfactory safety profile consistent with previous international reports.

Topics: Anemia; Combined Modality Therapy; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Anaemia management with erythropoiesis-stimulating agents (ESA) and i.v. iron replacement in haemodialysis patients poses several clinical challenges, including maintaining stable haemoglobin (Hb) levels within target ranges while achieving lowest effective ESA dose. This manuscript describes the effect of implementing proactive protocol-driven adjustments for iron and ESA in maintenance haemodialysis patients.. This was a cohort study of 46 satellite haemodialysis patients examined from 2004 to 2006 with protocol implementation in 2005. Baseline haemoglobin, transferrin saturations (TSAT), ferritin values and ESA administration were obtained during 2004. Follow-up data was collected in 2006 and compared to baseline values in reference to specified targets in the 2004 Caring for Australasians with Renal Impairment (CARI) guidelines.. Fifty-four percent of patients achieved haemoglobin targets during follow up versus 43% patients during baseline. Seventy-nine percent of patients achieved TSAT targets during follow up versus 67% patients during baseline. Ninety percent of patients achieved ferritin targets during follow up versus 75% patients during baseline. Odds ratios for values falling within target ranges during follow up compared to baseline were 1.63 (Hb: P = 0.037; 95% confidence interval (CI), 1.03-2.57), 1.90 (TSAT: P = 0.006; 95% CI, 1.20-3.01) and 3.72 (ferritin: P = 0.003; 95% CI, 1.57-8.83). There was a trend toward lower average ESA dose (P = 0.07).. This study demonstrates the successful implementation and efficacy of a proactive protocol for iron and ESA treatment in haemodialysis patients. Benefits include increased concordance with historical guideline targets and decreased haemoglobin variability. Improved iron status and optimizing ESA response allows for lower ESA doses, limiting both potential side-effects of ESA (hypertension) and the burgeoning costs of anaemia management.

Topics: Anemia; Biomarkers; Clinical Protocols; Cohort Studies; Community Health Centers; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Ferric Compounds; Ferritins; Guideline Adherence; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Odds Ratio; Practice Guidelines as Topic; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Time Factors; Transferrin; Treatment Outcome; Western Australia

ESAs are increasingly used to treat anemia of lower risk MDS, even before RBC transfusion requirement. From a previously published patient cohort treated with ESAs, we selected 112 patients with de novo low or int-1 IPSS MDS with Hb<10 g/dl, serum EPO<500 UI/l and who had never been transfused. Erythroid response rate at 12 weeks was 63.1% (IWG 2006). In multivariate analysis, an interval between diagnosis and ESA onset<6 months, Hb level>9 g/dl, and serum EPO<100 UI/l predicted better response to ESA while shorter interval between diagnosis and ESA onset (p=0.01), lower serum EPO (p=0.04) and WHO diagnosis of RCMD-RS (p=0.03) were associated with longer response. Median interval from diagnosis to transfusion dependency was 80 months and 35 months, respectively, in patients with onset of ESA < 6 months and ≥ 6 months from diagnosis (p=0.007). Those results support early onset of ESA in lower risk MDS, to better avoid the consequences of anemia. Early introduction of ESA may also delay the need for RBC transfusions, hypothetically by slowing the disease course, but prospective studies are required to further assess this point.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Recombinant Proteins; Retrospective Studies; Risk; Treatment Outcome

Darbepoetin alpha is effective for renal anemia when epoetin is insufficient. We previously reported that the dose conversion ratio from epoetin alpha to darbepoetin alpha was 1:350.5 after 24 weeks of follow-up. This study assessed the conversion ratio in stable Japanese hemodialysis patients after 52 weeks.. A total of 104 hemodialysis patients who were stable on intravenous epoetin alpha were switched to intravenous darbepoetin alpha according to the 1:200 rule. Then they were followed for 52 weeks to assess changes of hemoglobin and the darbepoetin alpha dose.. Eighty-five patients completed the study. Their hemoglobin increased very rapidly during the first 8 weeks. The final conversion ratio was 1:286.6 at 52 weeks. Darbepoetin alpha showed similar efficacy in diabetics and non-diabetics. Patients switching from a high epoetin alpha dose (> or =4500 IU/week) had a higher conversion ratio compared with those switching from a low dose (<4500 IU/week).. The dose conversion ratio of 1:200 was unsuitable and led to a rapid increase of hemoglobin. A conversion ratio of 1:250 to 1:300 should be employed when switching from epoetin alpha to darbepoetin alpha in Japanese patients.

Topics: Aged; Anemia; Asian People; Biomarkers; Darbepoetin alfa; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Dosage Calculations; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Japan; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome

Because of adverse survival effects, anemia management and financial incentives to increase doses of erythropoiesis-stimulating agents (ESAs) have been controversial. Prior studies showed more aggressive anemia management in dialysis facilities owned by for-profit chains, but have been criticized for not accounting for practices of individual physicians and facilities.. To improve understanding of how dialysis practices and resource utilization are influenced by physicians, facilities, and chains.. Mixed models with chain fixed effects and facility and physician random effects.. Medicare hemodialysis patients in 2004.. A total of 234,158 patients, 3995 facilities, 4838 physicians, and 7 chain classifications were included.. Spending per session for dialysis-related services billed separately from the dialysis treatment and for ESAs. Achievement of hematocrit (HCT) and urea reduction ratio (URR) targets.. Of the 4 largest for-profit chains, 3 had higher resource use than independents, with differences up to $17.92 higher ESA/session. Utilization was positively associated with achieving target HCT. Despite incurring lower costs, patients treated by a large nonprofit chain were as likely as patients of independents to achieve the HCT target. The largest chains were more likely than independents to achieve the URR target. Substantial variation occurred across physicians and facilities, and adjustment for chain only modestly decreased this variation.. Chains' methods of influencing practices were not directly observed.. Chains appear to have the ability to implement protocols that shift practices, but not the ability to substantially reduce local variation. Assertions that chain effects found by earlier studies were spurious are not supported.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ambulatory Care Facilities; Anemia; Drug Utilization; Epoetin Alfa; Erythropoietin; Health Care Costs; Health Resources; Hematinics; Humans; Medicare; Middle Aged; Models, Econometric; Multi-Institutional Systems; Private Sector; Recombinant Proteins; Renal Dialysis; United States

Epoetin alfa (EPO) and darbepoetin alfa are erythropoiesis-stimulating agents (ESAs) used to treat anemia in patients with chronic kidney disease. EPO and darbepoetin alfa have a non-proportional dose conversion relationship across the dosing spectrum. However, reports comparing the dose relationship between the two ESAs do not adjust for the non-proportional dose relationship or for population differences. Because drug cost is directly related to dosage, appropriate methods to assess the dose relationship between the two ESAs are important to understand the economic implications of converting patient populations from one ESA treatment to another.. To describe dose conversion methods that take into account the non-proportional dose relationship between EPO and darbepoetin alfa, and calculate the dose conversion ratio (DCR) between the two ESAs in a hospital-based dialysis patient population.. This was a retrospective observational study where longitudinal data from medical charts were collected for chronic hemodialysis patients being treated at hospital-based dialysis centers. Mean maintenance DCRs were calculated at the population level for hemodialysis patients converted from EPO to darbepoetin alfa treatment and subsequently maintained on darbepoetin alfa. Two methods were used to determine the DCRs: a regression-based method using ordinary least squares regression, and ratio-based method using an arithmetic mean.. The estimated population mean maintenance DCR for the population in this analysis was 320:1 (Units EPO:µg darbepoetin alfa) using the regression-based method, and 350:1 using the ratio-based method. Sensitivity analysis yielded DCRs ranging from 311 to 333:1.. The two methods in estimating the DCR presented here provide payers with an empirical way of comparing ESA utilization for pharmacoeconomic evaluation. DCR results may vary according to patient characteristics; however, mean DCRs of greater than 300:1 were obtained in this analysis. Exclusion of other patient-related factors that may influence ESA dose is a possible limitation of the study.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Dose-Response Relationship, Drug; Economics, Pharmaceutical; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemodialysis Units, Hospital; Humans; Kidney Diseases; Male; Medical Audit; Middle Aged; Recombinant Proteins; Regression Analysis; Retrospective Studies; Young Adult

Topics: Aged; Anemia; Chronic Disease; Epoetin Alfa; Erythropoietin; Female; Health Care Rationing; Hematinics; Humans; Insurance Coverage; Medicare; Recombinant Proteins; United States

A subgroup analysis comparing elderly (age > or =70 years; n=95) with younger (age <70 years; n=390) patients was performed on data from a prospective, multicenter, open-label study assessing the effects of once-weekly epoetin alfa 40,000 International Units (IU) for 16-20 weeks on hemoglobin (Hb) levels and quality of life (QoL) in anemic adult patients undergoing chemotherapy for solid tumors. There were significant increases in mean Hb levels at 4, 8, 12, 16-20 weeks in both age groups (p<0.0001), but no significant differences between groups (p=0.7). No significant difference was observed in terms of blood transfusion rates across the study between elderly and younger patients (3.2% vs 6.7%, p=0.2). Although QoL was lower in elderly patients at baseline, the relative percentage increases in QoL scores during treatment were similar for both age groups. Thus, once-weekly epoetin alfa was equally effective in treating chemotherapy-related anemia in elderly and younger adult patients, with similar tolerability.

Topics: Age Factors; Aged; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins

Compared to the intravenous route, subcutaneous administration of epoetin requires lower dose and will be an attractive option for cost containment when bundling for dialysis is implemented. Hemoglobin variability defined as fluctuation of hemoglobin over time has not been well studied with respect to the route of administration.. 157 prevalent-hemodialysis subjects were analyzed from an open-label, randomized study that compared the intravenous to the subcutaneous route of epoetin with identical weight-based dosing algorithm. Hemoglobin variability was defined as the number of weeks hemoglobin is outside the target range of 10-11 g/dl. Sensitivity analysis was performed.. 78 subjects in the intravenous and 79 in the subcutaneous group entered the 24-week dose maintenance phase. Baseline covariates were similar in both groups except for the dose of epoetin (lower in subcutaneous) and dialysis vintage (longer in intravenous). Patients on subcutaneous epoetin were outside the target range more weeks (p = 0.04) and had higher standard deviation of hemoglobin (p = 0.01) compared to the intravenous group.. The subcutaneous route of epoetin was associated with modestly higher hemoglobin variability, probably reflecting greater sensitivity of the subcutaneous route and/or identical epoetin-dosing algorithm employed in both the arms. This study could serve as an important guide when bundling for dialysis services is implemented as switching from intravenous to subcutaneous administration is likely to occur.

Topics: Aged; Anemia; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis

Anemia management remains complicated in patients with endstage renal disease on hemodialysis. We wished to evaluate the effect of protocol adherence to EPO and intravenous iron dosing on achieving the desired range of hemoglobin levels.. A cohort of hemodialysis patients was studied to evaluate the rate of adherence to EPO and iron dosing protocols over a 5 month period. A database was completed to evaluate all known comorbidities, demographic factors, and facility issues that might affect hemoglobin levels. A logistic regression model was employed to evaluate the effect of adherence to the anemia protocols on the probability of achieving a hemoglobin level below, within or above the targeted range of 11-12.5 g/dl.. Among 2114 patients, we found that adherence to both the EPO and iron dosing protocol resulted in the greatest probability of achieving the target hemoglobin range (56 +/- 5% in anemia protocol adherent patients versus 42 +/- 7% in non adherent patients). This was predominantly due to a lowered risk of having above target hemoglobin levels rather than below. The use of the anemia protocols was associated with lower rates of hospitalization (9 +/- 0.7 visits/100 months in adherent group vs 15 +/- 2 in non adherent group) and lower utilization of both EPO and intravenous iron. Furthermore, patients in the adherent groups had less variability of their hemoglobin levels month by month, at least as judged by standard deviation.. Adherence to anemia protocols, as practiced in the dialysis units included in this cohort, may improve hemodialysis patients' ability to achieve target hemoglobin levels, and by avoiding above target hemoglobin values, lower drug utilization and reduce variability of hemoglobin levels.

Topics: Aged; Anemia; Clinical Protocols; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Patient Compliance; Recombinant Proteins; Renal Dialysis; Retrospective Studies

In patients treated by maintenance hemodialysis the relationship to survival of hemoglobin level and administered epoetin-alfa and intravenous iron is controversial. The study aim was to determine effects on patient survival of administered epoetin-alfa and intravenous iron, and of hemoglobin and variables related to iron status.. The patients were 1774 treated by maintenance hemodialysis in 3 dialysis units in New York, NY from January 1998 to June, 2007. A patient-centered, coded, electronic patient record used in patient care enabled retrospective analysis of data collected prospectively. For survival analysis, patients were censored when transplanted, transferred to hemodialysis at home or elsewhere, peritoneal dialysis. Univariate Kaplan-Meier analysis was followed by multivariate analysis with Cox's regression, using as variables age, race, gender, major co-morbid conditions, epoetin-alfa and intravenous iron administered, and 15 laboratory tests.. Median age was 59 years, epoetin-alfa (interquartile range) 18,162 (12,099, 27,741) units/week, intravenous iron 301 (202, 455) mg/month, survival 789 (354, 1489) days. Median hemoglobin was 116 (110, 120)g/L, transferrin saturation 29.7 (24.9, 35.1)%, serum ferritin 526 (247, 833) microg/L, serum albumin 39.0 (36.3, 41.5) g/L. Survival was better the higher the hemoglobin, best with > 120 g/L. Epoetin-alfa effect on survival was weak but had statistically significant interaction with intravenous iron. For intravenous iron, survival was best with 1-202 mg/month, slightly worse with 202-455 mg/month; it was worst with no intravenous iron, only slightly better with > 455 mg/month. Survival was worst with transferrin saturation < or = 16%, serum ferritin < or = 100 microg/L, best with transferrin saturation > 25%, serum ferritin > 600 microg/L The effects of each of hemoglobin, intravenous iron, transferrin saturation, and serum ferritin on survival were independently significant and not mediated by other predictors in the model.. Long term survival of maintenance hemodialysis patients was favorably affected by a relatively high hemoglobin level, by moderate intravenous iron administration, and by indicators of iron sufficiency. It was unfavorably influenced by a low hemoglobin level, and by indicators of iron deficiency.

Topics: Adult; Aged; Anemia; Comorbidity; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hemoglobins; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Survival Analysis; Transferrin

No data exists that directly compares hemoglobin and hematocrit levels between cancer patients with and without occurrence of thrombosis during treatment with erythropoiesis stimulating agents (ESAs).. To determine the association of hemoglobin and hematocrit levels with the occurrence of thrombosis in cancer patients treated with ESAs.. A retrospective case-control study approved by the Institutional Review Board was conducted on cancer patients billed for epoetin or darbepoetin between 1 July 2002 and 30 June 2007. Cases were defined as patients billed for thrombosis while controls were defined as patients not billed for thrombosis.. Sixteen patients had an occurrence of thrombosis (cases) and were matched to 16 patients that did not have an occurrence of thrombosis (controls) based on age, sex, and cancer type. The mean peak hemoglobin levels for cases and controls were 12.6 +/- 1.2 g/dL versus 12.6 +/- 1.4 g/dL (p = 0.9). The mean peak hematocrit levels for cases and controls were 37.3 +/- 3.8% versus 37.9 +/- 4.3% (p = 0.8). For the 16/586 (2.7%) patients with thrombosis, the mean hemoglobin and hematocrit at time of thrombosis were 9.6 +/- 1.0 g/dL and 28.9 +/- 3.1%. A significant identifiable risk factor for thrombosis between the cases and controls was history of thrombosis 31.3% versus 0% (p = 0.04).. There was no statistical difference in peak hemoglobin and hematocrit levels between patients with thrombosis and those without thrombosis. Further study is warranted to determine if these levels are true risk factors for thrombosis.

Topics: Anemia; Anticoagulants; Case-Control Studies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies; Risk Factors; Thrombosis; Time Factors

Topics: Anemia; Critical Illness; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins

In patients with diabetes mellitus, hemoglobin A(1c) (A1C) is commonly interpreted as a measure of long-term glycemic control, reflecting a mean glucose level over the previous 2-3 months. Although some reports suggest that treatment with recombinant erythropoietin may affect A1C values in patients undergoing hemodialysis, we know of no evidence to support this interaction in patients with chronic renal insufficiency who are not undergoing hemodialysis. In addition, we know of no evidence specific to the treatment effect of epoetin alfa and/or darbepoetin alfa on A1C. We describe a 64-year-old man with diabetes, chronic kidney disease, and anemia who was treated consecutively with epoetin alfa and darbepoetin alfa and experienced a temporal reduction in A1C level to a nadir of 4.4%. Throughout approximately 3 years of treatment with these erythropoietin analogs, the patient's total daily dose of insulin was reduced in response to his decreasing A1C values, despite elevated blood glucose levels and the absence of patient-reported hypoglycemic events. Five months after the patient's erythropoietin therapy was discontinued, his A1C value increased to 8.8%, leading us to conclude that management of the insulin dose may have been different without the falsely lowered A1C levels. Use of the Naranjo adverse drug reaction probability scale indicated a probable association between this patient's reduced A1C levels and erythropoietin therapy. This case demonstrates that both epoetin alfa and darbepoetin alfa may artificially lower A1C levels in a patient with diabetes who is not undergoing dialysis, and therefore this finding can be interpreted as a class effect. Clinicians should be aware of factors that affect A1C values, specifically erythrocyte life span. In patients receiving erythropoietin, therapeutic decisions should be based on A1C and glucose levels, as well as patient symptoms suggestive of hypo- or hyperglycemia, to avoid therapy changes that could complicate disease management.

Topics: Anemia; Darbepoetin alfa; Diabetes Mellitus; Diabetic Nephropathies; Diagnostic Errors; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Glycated Hemoglobin; Hematinics; Humans; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

Topics: Anemia; Biopharmaceutics; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Health Care Costs; Hematinics; Humans; Recombinant Proteins; Red-Cell Aplasia, Pure; Risk Factors

Recombinant erythropoietin-stimulating agents have been used to ameliorate the symptoms of anaemia in cancer patients. However, there have been concerns about an increased risk of thromboembolic events and mortality. This study reviews the usage of epoetin alfa in treating chemotherapy-induced anaemia at the National Cancer Centre Singapore (NCCS), as well as the prescribing and monitoring practices employed.. Cancer patients who have received at least one dose of epoetin alfa at the NCCS between January 1, 2005 and October 15, 2007 were included in this study.. A total of 121 patients were identified and 91 patients were eligible for data collection. The majority of patients manifested breast cancer (30.8 percent) and ovarian cancer (15.4 percent). Over 90 percent of the patients were receiving either chemotherapy or radiotherapy when epoetin alfa was initiated. Epoetin alfa was initiated at a median haemoglobin level of 8.7 (range 7-14.3) g/dL. Approximately 41.8 percent of the patients had a positive response after the initiation of epoetin alfa. Baseline iron studies were performed in 12.1 percent of the patients. Blood pressure was uncontrolled, according to the Singapore Ministry of Health Hypertension guideline, in a substantial number of patients (32.6 percent) prior to the initiation epoetin alfa. There were no documented thromboembolic events.. This study identified a broad range of practices in the utilisation of epoetin alfa at NCCS, which may explain the variable patient response to epoetin alfa. The results of this study will be used to improve the management of chemotherapy-induced anaemia at the institution.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Cell Count; Blood Pressure; Blood Transfusion; Cancer Care Facilities; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobinometry; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies; Singapore; Utilization Review; Young Adult

Erythropoiesis stimulating agent (ESA) resource utilisation in cancer chemotherapy patients is of importance to managed-care organisations. To understand current real-world utilisation of ESAs, this study examined epoetin alfa (EPO) and darbepoetin alfa (DARB) treatment patterns (dosing and treatment duration), dose ratio and ESA treatment costs.. An analysis of medical claims data from January 2006 through to January 2008 was conducted using the PharMetrics Patient-Centric database of over 85 health plans. Patients included in the study were > or =18 years of age, had at least one cancer claim within 90 days prior to ESA treatment initiation, were newly initiated on EPO or DARB, received at least two doses, and were treated with concomitant chemotherapy (at least one chemotherapy claim during ESA treatment). Mean cumulative ESA dose was used to calculate drug cost (based on April 2008 wholesale acquisition cost) and dose ratio (units EPO : microg DARB).. A total of 4,111 EPO patients and 6,817 DARB patients met inclusion criteria and formed the study population. EPO-treated patients were slightly older (mean age: EPO 63.6, DARB 61.8, p<0.0001) with a greater proportion of women in the DARB-treated group (EPO 60.9%, DARB 64.1%, p=0.0007). The mean treatment duration was slightly longer in the EPO group (EPO 58.4 days, DARB 55.4 days, p=0.0019). The mean cumulative ESA dose administered was EPO 329,129 units and DARB 1,289 microg, resulting in a dose ratio of 255:1 (units EPO:microg DARB). Mean drug cost per treatment episode was significantly lower in the EPO group by $1,768 (EPO $4,321, DARB $6,089, p<0.0001). After controlling for covariates, the incremental cost associated with DARB treatment remained stable and statistically significant (adjusted cost difference: $1,806 per treatment episode higher for DARB patients than EPO, p<0.0001).. This study of 10,928 oncology patients receiving chemotherapy reported a dose ratio of 255:1 (units EPO:microg DARB) with 29% lower treatment cost in the EPO group. These findings are similar to those previously reported from published clinical trials and real-world utilisation studies.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Costs; Drug Utilization; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Insurance Claim Review; Male; Managed Care Programs; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies

To compare the baseline characteristics, episodes of care, and cost of erythropoiesis-stimulating agents among cancer patients in a US managed-care population.. Retrospective analysis of administrative claims data. Episodes of care for patients with cancer receiving erythropoiesis-stimulating agents between January 1, 2004 and January 17, 2006 included all claims for erythropoiesis-stimulating agents with < or = 42 days' gap between claims, plus the duration of therapeutic benefit based on median days between consecutive doses.. Main outcome measures were average weekly dose of erythropoiesis-stimulating agents and costs of therapy.. A total of 15,007 eligible episodes of care (darbepoetin alfa, 7769 episodes [5587 patients]; epoetin alfa 7238 episodes [5157 patients]) were identified. Fewer claims were observed per episode of care for darbepoetin alfa than for epoetin alfa (mean [SD] 3.7 [4.1] vs. 5.3 [6.4]). The median time between consecutive claims was 15 days (darbepoetin alfa) and 8 days (epoetin alfa). The mean (SD) weekly doses were 105 (56) microg (darbepoetin alfa) and 34,242 (28173) U (epoetin alfa), a dose-comparison ratio of 326 : 1. Dose-comparison ratios were sensitive to assumptions about duration of clinical benefit. The mean (95% CI) weekly costs were significantly lower for darbepoetin alfa ($560 [553-567]) than for epoetin alfa ($645 [630-659], p < 0.0001) when duration of clinical benefit was considered.. Significant differences characterize patterns of use of erythropoiesis-stimulating agents. Duration of therapeutic benefit is an important variable in comparing darbepoetin alfa with epoetin alfa; incorporation of this variable in analyses of costs of therapy may have notable effects on calculated treatment costs. Limitations of the study include the potential for database errors or omissions, lack of detailed disease data, and lack of adjustment for differences in the ages and comorbidities of patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Health Care Costs; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies; Treatment Outcome

We examined the association between high doses of Epoetin alfa (EPO), which are used to raise and maintain hemoglobin (Hb) levels within target ranges for hemodialysis patients, and short-term mortality risk using multivariable regression and an instrumental variable (IV) analysis.. We identified 32 734 patients receiving hemodialysis in 786 facilities from a large US dialysis provider between July 2000 and March 2002 who received care for >4 consecutive months, and had an Hb < 11 g/dL in the third month. We assessed dose titrations following the Hb < 11 g/dL and characterized facilities based on the percentage of patients with dose titrations >25% (instrument). We assessed deaths during the subsequent 90 days and evaluated the EPO dose-mortality association using conventional linear and IV regression.. The study population had a mean (SD) age of 60.4 (15.0) years; 48% were white, 42% were black and 51% were male. In unadjusted analyses, high EPO doses were associated with 90-day mortality risk (Risk Difference, RD = 3.0 per 100 persons, 95%CI:2.3-3.6); mortality risk was attenuated after adjustment for confounding (RD = 1.5 per 100 persons, 95%CI:0.8-2.2) and not associated with high EPO dose in the pooled IV analysis, though confidence intervals (CI) were wide (RD = -0.4 per 100 persons, 95%CI:-3.2-2.4).. The difference in risk estimates between the adjusted linear regression and the IV regression suggests that the short-term mortality related to EPO dosing may be largely attributable to confounding-by-indication for higher doses. The IV method, which was employed to address the possibility of residual confounding, yielded near null though imprecise effect estimates.

Topics: Aged; Anemia; Biomarkers; Confounding Factors, Epidemiologic; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Least-Squares Analysis; Linear Models; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United States

Two erythropoiesis-stimulating agents (ESAs), epoetin alfa and darbepoetin alfa, are approved for the treatment of chemotherapy-induced anemia in patients with cancer. Randomized controlled trials indicate that the drugs are similarly efficacious, but that the duration of clinical benefit (DCB) ranges from 2 to 7 days for epoetin alfa and from 7 to 21 days for darbepoetin alfa, depending on dose. Given equivalent efficacy, payers are increasingly interested in understanding the cost differences for these 2 drugs.. To examine the impact of different methodological approaches on the cost comparison between epoetin alfa and darbepoetin alfa users, with cancer from a payer perspective.. Episodes of care (episode) were constructed for cancer patients treated with ESAs, using MarketScan claims data. Episodes started with the first ESA claim and ended on the last ESA claim or the claim before a 42-day or longer gap in ESA therapy. Each episode was augmented with an estimated DCB based on the last dose in the episode. Cost was reimbursed amount observed in the claims database. Adjusted weekly cost was estimated using generalized linear models to control for difference in clinical and demographic differences across epoetin alfa and darbepoetin alfa episodes.. Episodes were created in 324 darbepoetin alfa and 342 epoetin alfa users. Darbepoetin alfa users tended to be younger, had more comorbidities, and had advanced cancer (all p < 0.001). After accounting for DCB, the average weekly cost of darbepoetin alfa was significantly lower than that of epoetin alfa ($619 vs $940; p < 0.001). After multivariate adjustment, darbepoetin alfa had lower costs than epoetin alfa in the base case and all alternative approaches.. To reduce the risk of potential bias, DCB and different patient characteristics should be taken into account when using retrospective claims data to conduct cost comparisons between agents that have significant differences in dosing schedule.

Topics: Age Factors; Aged; Anemia; Antineoplastic Agents; Comorbidity; Darbepoetin alfa; Databases, Factual; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Linear Models; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies

The erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) have comparable efficacy in treating chemotherapy-induced anaemia (CIA). Therapy choice depends on many factors, including cost. Previous estimates of ESA cost differences have been derived from claims data. These data lack clinical variables, such as baseline haemoglobin (Hb) level, which are likely to influence choice of ESA, dosing and costs. We estimated cost differences between DA and EA in patients with cancer receiving chemotherapy, using a propensity-score matched analysis of baseline patient characteristics with and without Hb values to assess the effect of this clinical variable on ESA cost estimates.. Data were extracted from electronic medical records in two US databases between January 2004 and December 2006. The study sample included 6743 patients receiving chemotherapy, with one or more visits during the study period, who received an ESA during a chemotherapy episode. Episodes of chemotherapy care were constructed using a 90-day gap in administration to identify the start and end. Patients receiving both DA and EA during their initial chemotherapy episode or with missing data were excluded, representing 42% of patients with CIA receiving an ESA. Drug costs were calculated from the cumulative dose multiplied by 106% of the average sales price (ASP) for DA or EA. Two propensity-score matches were conducted: first using variables available in administrative billing claims systems, then adding the baseline Hb test result. Regression-adjusted cost differences were estimated with and without baseline Hb, using generalized linear models.. Using baseline Hb levels resulted in a better match of the baseline characteristics for the EA and DA treatment groups than the original sample or the matched sample without Hb variables. Mean ESA costs (year 2007 values) for the original sample were $US4171 for EA and $US3811 for DA (mean difference $US360; p < 0.001, standard error [SE] $US99). With propensity-score matching without Hb variables, mean estimated costs were $US3836 for EA and $US3599 for DA (mean difference $US237; p = 0.053, SE $US123). With propensity-score match including Hb variables, mean costs were $US3965 for EA and $US3536 for DA (mean difference $US429; p = 0.001, SE $US125). Cost differences in sensitivity analyses ranged between $US102 (p = 0.201) and $US261 (p = 0.003).. Addition of baseline Hb level as a variable in propensity score and ESA cost models affects ESA treatment cost estimates in patients with cancer receiving chemotherapy. Cost comparisons based on observational data should use analytical methods that account for differences in clinical variables between treatment groups.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Databases, Factual; Drug Costs; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins; United States

To characterize the haemoglobin variability of haemodialysis, peritoneal dialysis and pre-dialysis patients treated with either epoetin alpha or darbepoetin alpha in a clinical setting where treatment was administered according to current standard Australian practice.. Data on haemodialysis, pre-dialysis and peritoneal dialysis patients were extracted from the Renal Anaemia Management database (RAM) from 1 January 2001 to 31 December 2004. The variance in haemoglobin was calculated from patient records with more than five haemoglobin observations over a period of at least 4 weeks following 9 weeks of therapy. A mixed-model was fitted to the within-patient variances and weighting was based on the number of observations minus 1 for each record.. The mean within-patient variance in haemoglobin levels for i.v. administered erythropoietin-stimulating agents (IV) haemodialysis, s.c. administered erythropoietin-stimulating agents (SC) haemodialysis, predialysis (SC) and peritoneal dialysis (SC) patients receiving epoetin alpha were 9% (95% CI: 13% to 5%, P < 0.0001), 17% (95% CI: 32% to 0.2%, P = 0.047), 19% (95% CI: 27% to 11%, P < 0.0001) and 26% (95% CI: 33% to 18%, P < 0.0001) lower than that for patients receiving darbepoetin alpha. The mean haemoglobin levels for haemodialysis (IV), haemodialysis (sc) predialysis (SC) and peritoneal dialysis (SC) patients receiving darbepoetin alpha were 11.6 g/dL, 11.2 g/dL, 11.5 g/dL and 11.5 g/dL compared with 11.5 g/dL, 11.6 g/dL, 11.7 g/dL and 11.5 g/dL for patients receiving epoetin alpha.. There was 9-26% greater within-patient fluctuation in haemoglobin levels in patients receiving darbepoetin alpha compared with epoetin alpha. The causes of haemoglobin fluctuations and the implications for patient outcomes and resource use require further study.

Topics: Aged; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Double-Blind Method; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematinics; Humans; Incidence; Male; Neoplasms; Prognosis; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Survival Analysis; Thromboembolism; Treatment Outcome

Erythropoiesis-stimulating agents (ESAs) are used in chemotherapy-induced anemia (CIA) with the goal of improving quality of life and preventing RBC transfusions. This retrospective database study compared the three currently available ESAs, epoetin alfa (EPO-A), epoetin beta (EPO-B), and darbepoetin alfa (DARB), regarding costs and outcomes.. Data were obtained from a Belgian longitudinal database, including medical and financial data on cancer patients receiving chemotherapy and ESAs, submitted by 46 Belgian hospitals. Propensity score matching was applied to correct for selection bias. The main effectiveness parameter was defined as transfusion- and anemia-readmission-free survival (TA-free survival) at 3 months. Costs were analyzed taking the health care payer perspective.. Including 1,584 EPO-A, 380 EPO-B, and 429 DARB propensity-matched patients, TA-free survival rates were similar for the three groups (DARB, 84.37%; EPO-A, 84.60%; EPO-B, 84.94%). Overall inpatient costs were euro 16,949 +/- euro 1,025, euro 19,472 +/- euro 901, and euro 19,295 +/- euro 1,048 for DARB, EPO-A, and EPO-B, respectively (DARB versus EPO-A, p < .0001 and DARB versus EPO-B, p = .008). Anemia-associated costs were euro 3,051 +/- euro 218 in the DARB group, compared with euro 3,995 +/- euro144 for EPO-A (p < .0001) and euro 3,752 +/- euro 229 for EPO-B (p = .0132).. To our knowledge, this is the first real-life matched retrospective study comparing ESAs with regard to both costs and effects. For similar patient profiles, the patients in the DARB group consumed the smallest amounts of ESAs, with similar clinical outcomes. These data therefore suggest a greater efficiency of DARB in the treatment of CIA.

Topics: Aged; Anemia; Antineoplastic Agents; Belgium; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Health Care Costs; Hematinics; Humans; Length of Stay; Male; Middle Aged; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Treatment Outcome

The target of renal anemia correction with erythropoietin stimulating agents (ESAs) has been traditionally set at a hemoglobin (Hb) level of 11 - 12 g/dL. However, a trend has arisen of progressively increasing the Hb level to beyond 12 g/dL. Recent randomized control trials (RCTs) on correction of renal anemia in chronic kidney disease patients found that normalization of anemia to above 13 g/dL was associated with negative outcome parameters, echoing a previous RCT that showed increased death and myocardial infarction risk after normalization of hemoglobin level in hemodialysis patients. The latest consensus is to limit Hb to a level not exceeding 13 g/dL during renal anemia correction with ESAs. Currently, there are three ESAs available commercially. The choice of ESA should consider safety of subcutaneous administration, cost-effectiveness, and dosing frequency, all of which may affect compliance with ESA administration. Early identification of, and an early search for the causes of hyporesponsiveness to, ESAs is needed to avoid unnecessary escalation in the dose of ESAs. These approaches will help to improve the cost-effectiveness of ESA therapy and permit early detection of hidden problems. The current definitions of hyporesponsiveness are far too stringent and should be reviewed.

Topics: Anemia; Cost-Benefit Analysis; Drug Monitoring; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobinometry; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Peritoneal Dialysis; Randomized Controlled Trials as Topic; Recombinant Proteins; Trace Elements; Treatment Outcome

Topics: Aged; Aged, 80 and over; Anemia; Cyclosporine; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Male; Recombinant Proteins; Red-Cell Aplasia, Pure

Topics: Anemia; Chronic Disease; Drug Administration Schedule; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Diseases; Patient Selection; Recombinant Proteins; Treatment Outcome

Anemia is frequently observed in patients with chronic heart failure (CHF) and is related to an impaired outcome. The origin of anemia in CHF is diverse and is associated with several factors including renal failure, resistance of the bone marrow to erythropoietin (EPO), hematinic deficiencies, and medication use. Recently, several small-scale clinical trials have shown that EPO treatment might improve clinical parameters in anemic heart failure patients. In addition, several preclinical studies have shown that EPO possesses non-hematopoietic effects. This current review focuses on the etiology, consequences, and treatment of anemia in heart failure patients. The pleiotropic effects of EPO in an experimental setting will also be discussed. Heart Fail Monit 2008;6(1):28-33.

Topics: Anemia; Bone Marrow; Chronic Disease; Epoetin Alfa; Erythropoietin; Heart Failure; Humans

The primary aim of this study was to assess whether epoetin alpha (Ea) would improve cognitive performance in a group of anaemic cancer patients receiving chemotherapy. The secondary aim was to confirm the positive impact of Ea on haematological parameters, and quality of life (QOL). Fifty patients with solid tumours and haemoglobin (Hb) <11.0 g/dL received Ea 40,000 units once weekly for 12 weeks and were administered the Mini-Mental State Examination and the European Organization for Research and Treatment of Cancer (QLQ-C30) questionnaire prior to Ea therapy and at study completion. No clinically significant alterations were observed on cognitive function during Ea treatment. Changes in cognitive function were unrelated to Hb change and there were no significant differences in cognitive performance between Ea responders and non-responders. The analyses revealed clinically significant improvements in Hb levels, physical and role function, and clinically meaningful reductions in fatigue. Hb changes were significantly associated with the magnitude of improvement in QOL parameters. The lack of a clinical benefit in cognition observed in this study during Ea treatment may redirect the focus of research from enhancing to maintaining cognitive function, since stability in cognitive performance through time may be as well clinically important.

Topics: Adolescent; Adult; Aged; Anemia; Antineoplastic Agents; Chemotherapy, Adjuvant; Cognition Disorders; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Treatment Outcome; Young Adult

Erythropoiesis-stimulating agent (ESA) use in the outpatient and inpatient settings through pharmacist-conducted, hospital-based chart audits is examined and discussed.. Data from four hospital chart audits conducted in 250 hospitals between October 2005 and July 2006 were pooled for analyses. Eligible hospitals were categorized by ESA sales volume, with approximately equal numbers randomly selected from each decile. The last five inpatients and outpatients within each specified month receiving either darbepoetin alfa or epoetin alfa were evaluated. Study variables by setting included ESA use, prescriber specialty, and dosage regimen.. The most common hospital locations of ESA administration were a cancer center in the outpatient setting (49%) and general medicine (57%) in the inpatient setting. ESA prescribers were most commonly hematologists and oncologists in the outpatient setting, and nephrologists were the most common prescribers in the inpatient setting. In the outpatient analysis, 2155 patients were prescribed darbepoetin alfa and 3106 were prescribed epoetin alfa. The predominant administration frequencies were every two weeks and once weekly for darbepoetin alfa, and once weekly for epoetin alfa. In the inpatient analysis, 1633 patients were prescribed darbepoetin alfa and 3231 were prescribed epoetin alfa. The predominant administration frequencies were once weekly for darbepoetin alfa and once weekly and three times weekly for epoetin alfa. Common uses for both ESAs were chemotherapy-induced anemia (outpatient setting) and anemia of end-stage renal disease with chronic dialysis (inpatient setting). There was considerable variability in ESA dosages and administration frequencies in both settings within all patient groups when analyzed by specified use.. ESA use differed between outpatient and inpatient settings in indication, frequency of administration, and specialty of the prescriber.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Utilization Review; Epoetin Alfa; Erythropoietin; Hematinics; Hospital Bed Capacity, 100 to 299; Hospitals; Humans; Inpatients; Outpatients; Practice Patterns, Physicians'; Recombinant Proteins; Renal Insufficiency, Chronic; United States

Topics: Aged; Anemia; Causality; Chronic Disease; Cross-Over Studies; Double-Blind Method; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobinometry; Humans; Kidney Failure, Chronic; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins

Observational studies have consistently documented independent, strong associations of anemia--even if not severe--with major adverse functional outcomes in older adults. In this chapter, recent epidemiologic evidence linking mild anemia with decline in physical and cognitive function, frailty, and disability in community-dwelling older adults is reviewed. Altogether, these biologically plausible associations provide empirical, though not conclusive, support for the notion of mild anemia as a cause of adverse functional outcomes in older adults. Randomized clinical trial data assessing the impact of anemia correction on functional outcomes are lacking at this time.

Topics: Activities of Daily Living; Adult; Aged; Aging; Alzheimer Disease; Anemia; Cognition; Epoetin Alfa; Erythropoietin; Female; Frail Elderly; Hematinics; Hemoglobins; Humans; Male; Physical Fitness; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Labeling; Drug Prescriptions; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Europe; Hematinics; Humans; Neoplasms; Recombinant Proteins; United States; United States Food and Drug Administration

Topics: Anemia; Darbepoetin alfa; Drug Labeling; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins; United States; United States Food and Drug Administration

Guidelines for management of patients with myelodysplastic syndromes (MDS) have been generated by the National Comprehensive Cancer Network (NCCN) Myelodysplastic Syndromes Panel. Because MDS is a heterogeneous spectrum of disorders, these patients have been categorized into prognostic subgroups, predominantly using the International Prognostic Scoring System (IPSS). Several drugs have been used to treat these patients, and their selection and sequential recommended use by the panel depend on disease characteristics and responses to treatment. Recombinant erythropoietin alfa and darbepoetin alfa have been the mainstay of therapy for treating anemia associated with MDS. The FDA has recently approved several other drugs for treating MDS, including azacytidine and decitabine for all stages of disease, lenalidomide for low-risk anemic patients with del(5q) chromosomal abnormality, and deferasirox for treating iron overload. For iron chelation, deferoxamine is also used occasionally. Treatment with immunosuppressive therapy (antithymocyte globulin and cyclosporin) has been therapeutically beneficial for a subset of younger patients with MDS. Because the financial cost of these therapies are substantial and have received only limited attention, this article evaluates the costs of specific drugs and their sequential use in the lower-risk IPSS (low and intermediate-1) subgroups based on the NCCN guidelines. Results estimate an average annual cost for potentially anemia-altering drugs of $63,577 per patient, ranging from $26,000 to $95,000, depending on the specific therapies. In patients for whom the therapies fail, annual costs for iron chelation plus red blood cell transfusions are estimated to average $41,412. The economic impact of drug therapy should be weighed against the patient's potential for improvement in clinical outcomes, quality of life, and transfusion requirements.

Topics: Anemia; Antineoplastic Agents; Azacitidine; Cost of Illness; Costs and Cost Analysis; Darbepoetin alfa; Decision Support Techniques; Deferoxamine; Drug Costs; Drug Therapy; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Iron Chelating Agents; Lenalidomide; Myelodysplastic Syndromes; Practice Guidelines as Topic; Recombinant Proteins; Siderophores; Thalidomide; United States

The treatment of chemotherapy associated anemia in patients with cancer has varied greatly in recent years. The objective of this study was to verify whether the most frequently used therapeutic schedules of erythropoietin administration demonstrate equivalent effectiveness.. Treatments corresponding to 1,103 patients with cancer receiving treatment with erythropoietic colony-stimulating factors from January 2003 to April 2006 were reviewed. After applying a selection algorithm, 170 cases were analysed: 55 treated with epoetin alpha 10,000 IU 3 times per week, 63 receiving darbepoetin alpha 150 microg weekly and 52 treated with darbepoetin alpha 500 microg every 3 weeks. The main variables used to compare effectiveness were the increase in serum hemoglobin levels during treatment and the percentage of patients with hemoglobin values > or = 120 g/l.. The differences in maximum hemoglobin values achieved at baseline and during the study period, and those between the final and baseline hemoglobin values were similar in the 3 groups. The percentage of patients with hemoglobin values > or = 120 g/l during and at the end of treatment was equivalent for the group receiving epoetin alpha 10,000 IU three times per week and darbepoetin alpha 150 microg per week. However this parameter war inferior for the group treated with darbepoetin alpha 500 microg every 3 weeks.. Epoetin alpha 10,000 IU 3 times per week was found to be as effective as darbepoetin alpha 150 microg per week in all the studied parameters, while darbepoetin alpha 500 microg every 3 weeks was not in one of them.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies

Treatment of the anemia of chronic kidney disease (CKD) with erythropoiesis-stimulating agents (ESAs) has been intensely debated during the past 2 years. Treatment with ESAs has transformed the lives of millions of patients with CKD, with fewer blood transfusions and improved quality of life. However, randomized trials have suggested that targeting greater hematocrits/hemoglobin levels and/or exposure to high doses of ESAs is associated with a greater risk of cardiovascular complications and mortality. The US Food and Drug Administration has inserted a boxed warning for ESAs and, along with the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI), decreased recommended target hemoglobin ranges for ESA therapy. The Centers for Medicare & Medicaid Services has decreased ESA dosing recommendations in the Medicare claims policy for ESAs. Managing the anemia of CKD in the era of the hemoglobin level and ESA controversy has required aiming for appropriate hemoglobin levels, using the lowest effective ESA dose, and better managing the problem of ESA hyporesponsiveness.

Topics: Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Medicaid; Medicare; Recombinant Proteins; United States; United States Food and Drug Administration

Topics: Anemia; Black or African American; Chronic Disease; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Diseases; Recombinant Proteins; White People

A subgroup of hemodialysis patients experience high serum ferritin and low tansferrin saturation for reasons not clearly understood. Here we determined the economic impact of administering sodium ferric gluconate complex to patients with serum ferritin levels higher than 500 ng/ml and a transferrin saturation less than 25% based on the Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study and its extension, DRIVE II. A cost effectiveness model was developed, consistent with the DRIVE studies, using decision analysis with a 12-week time horizon. The primary effectiveness measure was the mean hemoglobin increase in the intent to treat patient groups comparing epoetin with or without sodium ferric gluconate complex. Costs were computed using projected 2007 US Medicare reimbursements for the treatments and for serious adverse events, with the effectiveness factored by the increase in hemoglobin. The net savings for sodium ferric gluconate complex plus epoetin treatment was $1390 compared to epoetin alone for each g/dl hemoglobin increase over 12 weeks of study. Sensitivity analyses were performed to test the impact of change in the variables (using medians or means and actual 2005 or projected 2007 Medicare reimbursements) and these affirmed the robustness of the model. Our study shows that treatment of patients with high ferritin and low transferrin saturation levels, as defined in DRIVE, with sodium ferric gluconate complex and epoetin resulted in significant savings compared to epoetin alone.

Topics: Adult; Aged; Algorithms; Anemia; Cost Savings; Drug Costs; Epoetin Alfa; Erythropoietin; Ferric Compounds; Ferritins; Hematinics; Hemoglobins; Humans; Kidney Diseases; Medicare; Middle Aged; Recombinant Proteins; Renal Dialysis; United States

Topics: Anemia; Cost-Benefit Analysis; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Japan; Recombinant Proteins; Renal Dialysis

Anemia is a common comorbid condition among patients admitted to the intensive care unit (ICU). Darbepoietin alfa and epoetin alfa are erythropoiesis-stimulating agents (ESAs) used to manage anemia in the ICU, although neither drug has an indication in critically ill patients.. This study describes ESA practice patterns in anemic, critically ill patients admitted to the ICU.. A total of 19 hospitals participated in this US multicenter, retrospective, observational study of adult patients not receiving chronic hemodialysis who were admitted to the ICU for >or=24 hours between February 2005 and September 2005 and who received >or=1 dose of darbepoietin alfa or epoetin alfa. Data on ESA doses, dosing frequencies, hemoglobin levels, and red blood cell (RBC) transfusions were abstracted from electronic medical records.. A total of 438 patients were included in the analysis, of whom 201 (46%) were treated with darbepoietin alfa and 237 (54%) were treated with epoetin alfa. In the respective groups, similar proportions were male (121/201 [60%] and 126/237 [53%]) and white (146/195 [75%] and 140/184 [76%]); age was also similar (mean [SD], 62 [19] and 60 [18] years). The mean (SD) dose during the first week of ICU stay was 96.5 (40.5) microg with darbepoietin alfa and 33,439 (23,508) U with epoetin alfa. The most commonly prescribed dosing frequency with darbepoietin alfa was once weekly (88.1% of all prescribed doses), with a mean (SD) number of injections of 1.8 (1.75). With epoetin alfa, the most common dosing frequencies were 3 times weekly (35.9%), 1-time dosing (28.5%), and once weekly (24.0%), with a mean (SD) number of injections of 2.9 (4.2). In both groups, the duration of therapy was

Topics: Adult; Aged; Aged, 80 and over; Anemia; Cohort Studies; Critical Illness; Darbepoetin alfa; Drug Utilization Review; Epoetin Alfa; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Patient Admission; Recombinant Proteins; Retrospective Studies; Time Factors; United States

This analysis was conducted to compare the direct medical costs of treatment with darbepoetin alfa every 3 weeks (Q3W) and epoetin alfa every week (QW) in patients with chemotherapy-induced anaemia (CIA) from the payer's perspective.. An analysis was conducted from a US health plan perspective to compare the annual budget impact for CIA with darbepoetin alfa Q3W and epoetin alfa QW over a 16-week treatment period. Dosing regimens were obtained from registration clinical trials.. Mean doses, including dose adjustments, were 375.6 microg Q3W for darbepoetin alfa and 43,187 U QW for epoetin alfa. Costs of medical resources included drug acquisition and administration costs. The base case analysis resulted in a per-patient budget impact of $8,544 and $8,667 for darbepoetin alfa and epoetin alfa, respectively. Per member per month cost was $0.90 for darbepoetin alfa and $0.91 for epoetin alfa, based on an estimate of 2,735 CIA patients in a health plan population of 2.17 million. The analysis was most sensitive to drug dose, treatment period and drug price.. Results suggest that per-patient direct medical costs of CIA treatment, when initiated at labelled starting doses, are comparable for darbepoetin alfa Q3W and epoetin alfa QW.

Topics: Anemia; Budgets; Darbepoetin alfa; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Health Expenditures; Hematinics; Humans; Recombinant Proteins; Taxes; United States

Anaemia is a common complication of renal failure. It can be treated with erythropoietin (EPO) administration, red blood cell transfusion (RBCT), or a combination of both. EPO has been registered for the treatment of renal anaemia in Sweden since the beginning of the 1990s, and is the primary treatment regimen for anaemia related to renal failure. The objective of this study was to carry out a cost-effectiveness analysis from a provider perspective of a treatment strategy comprising EPO and complementary RBCT compared to the traditional treatment of RBCT alone for patients with anaemia associated with renal failure in Sweden.. Incremental costs and quality-adjusted life-years (QALYs) associated with EPO (epoietin-alpha) treatment compared to the traditional therapy of RBCT were estimated. The QALY gains were estimated using a modified version of a Markov model, which is used by the UK National Institute of Clinical Excellence in their evaluations of EPO treatment in the UK. Swedish treatment practice (i.e. EPO doses and iron supplementation), patient characteristics and unit costs were used throughout the study.. The estimated cost per QALY gained from administration of EPO to renal patients falls within the range acceptable in Sweden for both haemodialysis and peritoneal dialysis patients.. EPO administration to renal patients is much more costly in Sweden than in the UK, primarily due to the higher dosage of EPO and iron supplementation used in Sweden. However, Swedish patients reach higher haemoglobin levels, and thereby achieve higher QALY gains, compared to patients in the UK.

Topics: Anemia; Cost-Benefit Analysis; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Health Care Costs; Hematinics; Humans; Male; Middle Aged; Recombinant Proteins; Renal Insufficiency; Sweden; Treatment Outcome

To update the American Society of Clinical Oncology/American Society of Hematology (ASCO/ASH) recommendations for the use of epoetin. The guideline was expanded to address use of darbepoetin and thromboembolic risk associated with these agents.. An Update Committee ("Committee") reviewed and analyzed data published since 2002 through July 2007. MEDLINE and the Cochrane Collaboration Library databases were searched.. For patients with chemotherapy-associated anemia, the Committee continues to recommend initiating an erythropoiesis-stimulating agent (ESA) as hemoglobin (Hb) approaches, or falls below, 10 g/dL, to increase Hb and decrease transfusions. ESA treatment continues to be recommended for patients with low-risk myelodysplasia for similar reasons. There is no evidence showing increased survival as a result of ESA treatment. Conclusive evidence is lacking that, absent clinical circumstances necessitating earlier treatment, initiating ESAs at Hb levels greater than 10 g/dL either spares more patients from transfusion or substantially improves their quality of life. Starting doses and dose modifications based on response or lack thereof should follow the package insert. Continuing ESAs beyond 6 to 8 weeks in the absence of response, assuming appropriate dose increase has been attempted in nonresponders as per US Food and Drug Administration-approved labeling, does not seem to be beneficial, and ESA therapy should be discontinued. The Committee recommends monitoring iron stores and supplementing iron intake for ESA-treated patients. ESAs should be used cautiously with chemotherapy, or in clinical states, associated with elevated risk for thromboembolic complications. The Committee also cautions against ESA use for patients with cancer who are not receiving chemotherapy, since recent trials report increased thromboembolic risks and decreased survival under these circumstances.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Hematinics; Humans; Neoplasms; Recombinant Proteins; Societies, Medical

Nearly all dialysis patients receive epoetin therapy to treat anemia. Using the United States Renal Data System, we monitored the 14,001 patients aged 65 and older who started dialysis and epoetin treatment in 2003-2004. We estimated the dose-response relationship for the average epoetin dose and hematocrit during a 3-month initiation and subsequent 3-month maintenance phase using a marginal structural model to adjust for measured time-dependent confounding by indication. During the initiation phase, an S-shaped dose-response relationship for average weekly epoetin dose and hematocrit response was found. Average hematocrit levels rose as the epoetin dose was increased from 9,000 to approximately 22,500 units per week. At higher doses, the effect of increasing epoetin was minimal with average hematocrit levels plateauing at 38.5%, but this was less evident in the maintenance phase. Among patients who reached this phase, doses required to maintain the hematocrit level were lower than those required to achieve similar hematocrit levels in the initiation phase. The dose-response curve found in our study suggests that published recommendations for starting dose are appropriate, and a starting dose of 7,500-15,000 units per week can maintain the hematocrit level in the desired target range of 33-36%.

Topics: Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Humans; Kidney Failure, Chronic; Male; Models, Biological; Recombinant Proteins; Renal Dialysis

Unlike in outpatient settings, the comparative costs of epoetin alpha (EPO) and darbepoetin alpha (DARB) have not been evaluated broadly from the inpatient hospital perspective.. To develop a cost analytic model comparing hospital inpatient costs for erythropoiesis stimulating therapies within the nephrology and oncology settings.. A cost analytic model incorporating erythropoietic drug, pharmacy, and nursing costs was developed from the inpatient hospital perspective to evaluate comparative costs of EPO and DARB. Erythropoietic drug costs were calculated using unit wholesale acquisition cost multiplied by the number of units or micrograms while comparing the following dosing regimens: EPO 3 times weekly, EPO once weekly, and DARB once weekly. Pharmacy costs included dispensing and delivery costs, while nursing costs incorporated administration time costs; all were calculated by estimated fractional hours per activity multiplied by hourly wages. The total frequency of erythropoiesis stimulating therapy administrations was determined based on the average hospital length of stay. The first erythropoiesis stimulating therapy dose was assumed to occur on day 3 of hospitalization. For total inpatient costs, a weighted average was calculated across disease states. One-way sensitivity analyses were conducted by varying length of stay, day of initial erythropoiesis stimulating therapy dose, pharmacy and nursing costs, and once-weekly DARB dose.. EPO 3 times weekly was the least costly regimen across all disease states evaluated. Threshold analysis indicated that the cost of once-weekly DARB regimens would have to be reduced by 37% to equal the cost of EPO 3 times weekly for an average length of stay. Sensitivity analyses did not considerably affect the results.. EPO 3 times weekly was found to be the least costly erythropoiesis stimulating therapy regimen for nephrology and oncology inpatients for the average length of stay as well as most other lengths of stay considered. Once-weekly EPO was the least costly erythropoiesis stimulating therapy regimen for several other lengths of stay, while once-weekly DARB was never found to be the least costly regimen.

Topics: Anemia; Costs and Cost Analysis; Darbepoetin alfa; Drug Costs; Epoetin Alfa; Erythropoietin; Hematinics; Hospital Costs; Humans; Length of Stay; Models, Economic; Nursing Service, Hospital; Pharmacy Service, Hospital; Recombinant Proteins

Topics: Adrenal Cortex Hormones; Anemia; Critical Illness; Drug Interactions; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Receptors, Erythropoietin; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Follow-Up Studies; Heart Failure; Hematocrit; Humans; Kidney Failure, Chronic; Myocardial Infarction; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis; Survival Analysis

To report the design, methodology, implementation and initial results of the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) Registry, the first US patient registry to collect and report on practice patterns and outcomes associated with erythropoiesis-stimulating therapy (EST) for anaemia management in oncology patients.. DOSE is a prospective ongoing registry of oncology patients treated with epoetin-alpha or darbepoetin-alpha. Patients from either community or academic centres who meet prespecified entry criteria are eligible for inclusion in the registry. Data collected include patient demographic and clinical characteristics, EST administration, haematological parameters, patient-reported outcomes and medical resource utilization. Patients are followed from EST initiation through to the end of therapy or 16 weeks, whichever is earlier.. Initial results from 45 sites for 861 patients (epoetin-alpha, n = 312; darbepoetin-alpha, n = 549) showed that baseline demographic and disease characteristics were similar between the two treatment groups. Administration of EST at both weekly and > or =2-weekly intervals was observed in both groups, with similar numbers of haemoglobin determinations. However, the mean number of office visits was higher in the darbepoetin-alpha group despite more frequent administration of therapy at > or =2-weekly intervals in this group. Mean treatment duration was approximately 8 weeks for both groups. Mean post-baseline haemoglobin levels of 11-12 g/dL were achieved and maintained at all timepoints assessed with epoetin-alpha but not with darbepoetin-alpha. Both groups had similar rates of packed red blood cell transfusions.. The DOSE Registry is a valuable source of data relating to anaemia management, practice patterns and outcomes in oncology patients from the perspective of actual clinical practice. Results from this registry should provide patients, clinicians and healthcare decision makers with a better understanding of the relationship between EST dosage and outcomes in the clinical setting.

Topics: Aged; Anemia; Darbepoetin alfa; Databases, Factual; Epoetin Alfa; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Internet; Iron; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins; Registries; Treatment Outcome; United States

Patients with cancer may receive erythropoiesis-stimulating agents (ESAs), including darbepoetin alfa (DA) or epoetin alfa (EA), to treat cancer-related anemia (CRA). DA and EA differ, however, with respect to their assumed duration of effect and thus their approved frequency of dosing, complicating direct comparison of their doses and costs.. The objective of this study was to examine, from the perspective of a third-party payer, patterns of use and costs of DA and EA in patients with CRA, using episode-based methodology to account for differences in assumed duration of effect and frequency of dosing with these products.. Using a large US health insurance claims database, we identified all patients with cancer who received ESAs between January 1, 2005, and June 30, 2005 (study period). For each such patient, we identified all unique episodes of care (EOCs) with DA or EA, and then compared mean weekly dose and cost of ESA therapy within these EOCs, which were calculated using the ratio of total dose received and total cost of ESA therapy, respectively, to total EOC duration; only the first EOC for each patient was considered. EOCs were assumed to begin on the date of first ESA administration within the study period, and end on the date of final ESA administration (within the episode) plus an assumed duration of effect based on the ESA received and corresponding dose. We also estimated the ratio of mean weekly dose of EA (in units) to mean weekly dose of DA (in micrograms) (EA/DA weekly dose ratio). Multivariate regression was used to control for differences in baseline characteristics of EA and DA patients.. We identified a total of 1226 patients with complete EOCs with ESAs (EA, 381; DA, 845). DA patients were more likely to have had evidence of receipt of chemotherapy (54% vs 47% for EA; P = 0.02); they also had more comorbidities (mean Charlson comorbidity scores, 4.3 and 3.9, respectively; P < 0.01). Estimated mean (95% CI) weekly dose within EOCs was 97 microg (94-99) for DA, and 43,184 U (40,181-46,589) for EA; EA/DA weekly dose ratio was 445:1. Adjustment for differences in patient characteristics yielded a slightly lower ratio (403:1). Results were sensitive to the exclusion of EOCs consisting of a single administration of ESA therapy and/or the addition of an assumed duration of effect to the final ESA dose administered.. Cost comparisons of DA and EA are sensitive to the assumed duration of effect added to the final dose of ESA therapy, especially for EOCs with relatively few administrations.

Topics: Adolescent; Adult; Aged; Anemia; Comorbidity; Darbepoetin alfa; Databases, Factual; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; United States

Our aim was to evaluate red blood cell (RBC) membrane protein composition in chronic kidney disease (CKD) stage 5 patients under haemodialysis (HD) and recombinant human erythropoietin (rhEPO) therapy, and its linkage to rhEPO hyporesponsiveness. We evaluated in 63 CKD stage 5 patients (32 responders and 31 non-responders to rhEPO therapy) and in 26 healthy controls RBC count, haematocrit, haemoglobin concentration, haematimetric indices, reticulocyte count, reticulocyte production index, RBC osmotic fragility test and membrane protein analyses. CKD stage 5 patients presented significant changes in membrane protein composition, namely a reduction in spectrin, associated to altered protein 4.1/spectrin and spectrin/band 3 ratios. Non-responder CKD stage 5 patients were more anaemic, with more microcytic and anisocytic RBCs, than responders; significantly altered ankyrin/band 3 and spectrin/ankyrin ratios were also observed. CKD stage 5 patients under HD are associated with an altered protein membrane structure, which seems to the disease itself and/or to the interaction with HD membranes.

Topics: Aged; Anemia; Anion Exchange Protein 1, Erythrocyte; Ankyrins; Blood Proteins; Darbepoetin alfa; Diabetic Nephropathies; Drug Resistance; Epoetin Alfa; Erythrocyte Membrane; Erythropoietin; Female; Folic Acid; Humans; Iron; Kidney Failure, Chronic; Male; Membrane Proteins; Membranes, Artificial; Middle Aged; Oxidation-Reduction; Recombinant Proteins; Renal Dialysis; Spectrin

Topics: Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Our objective was to determine whether patient factors, processes of care and measures of erythropoietin (EPO) responsiveness were associated with successful anemia management at the individual patient level.. We retrospectively reviewed laboratory and demographic data from 1499 patients receiving hemodialysis in 15 units operated by the same dialysis provider. We performed univariate and multivariate logistic regression analysis to determine predictors of an average 3-month hemoglobin level below or above the target interval of 11.0-12.5 g/dL. To explain the effect of facility on anemia performance, we calculated correlations between measures of EPO responsiveness and the probability of achieving the target interval by facility.. Patients above the target hemoglobin range demonstrated an association with parathyroid hormone (PTH) (OR = 0.96 per 100 pg/mL increase), female gender (OR = 0.68), EPO protocol use (OR = 0.94 per 10% increase in use) and facility (range of OR = 0.26-2.59 for 15 participating sites). Patients below the target hemoglobin range demonstrated an association with CRP (OR = 1.10 per mg/L increase), PTH (OR = 1.07 per 100 pg/mL increase), iron deficiency (OR = 1.07 per 10% increase), EPO protocol use (OR = 0.89 per 10% increase in use), iron protocol use (OR = 0.93 per 10% increase in use) and facility (range of OR = 0.58-3.41 over 15 units). EPO index (r = 0.71), EPO dose (r = 0.73), hemoglobin (r = -0.60) and EPO per unit weight (r = 0.76) were significantly correlated with the probability of achieving the target hemoglobin by facility.. The facility significantly influences the outcome of anemia management in patients with ESRD. In part, this is due to the patients' EPO responsiveness, which may be influenced by facility care patterns.

Topics: Anemia; C-Reactive Protein; Epoetin Alfa; Erythropoietin; Health Facilities; Hemoglobins; Humans; Kidney Failure, Chronic; Linear Models; Logistic Models; Odds Ratio; Organizations, Nonprofit; Recombinant Proteins; Renal Dialysis; Retrospective Studies

This study assessed the employer cost burden of predialysis CKD-related anemia for a major US manufacturer, by examining indirect and direct costs before and after initiation of epoetin alfa (EPO).. Hemoglobin (Hb) levels, direct costs, and indirect costs for employees with CKD-related anemia were collected for 15 months (9 months pre-EPO and 6 months concurrent/post-EPO treatment). Indirect costs (absenteeism and presenteeism) and direct costs (medical and pharmacy) were compared for the pre- and post-EPO treatment periods.. Treating CKD-related anemia with EPO increased Hb levels from 9.4 (1 to 3 months pre-EPO)to 12.2 g/dL (4 to 6 months post-EPO), decreased absenteeism by 52.3 days per patient per year (PPPY), increased productivity by 91.5% PPPY, and reduced health care costs by approximately $4417 PPPY.. Among employees with predialysis CKD-related anemia, EPO treatment was associated with increased Hb levels, improved productivity, and decreased direct employer costs.

Topics: Aged; Analysis of Variance; Anemia; Cohort Studies; Comorbidity; Deductibles and Coinsurance; Efficiency, Organizational; Employer Health Costs; Epoetin Alfa; Erythropoietin; Female; Health Services; Hematinics; Hemoglobins; Humans; Industry; Kidney Failure, Chronic; Male; Middle Aged; Occupational Health; Recombinant Proteins; United States

The paper describes the need for the introduction of an anaemia management algorithm. It discussed the problems which the unit had in constant reviewing and re-prescribing ESA to maintain optimum haemoglobin levels for the unit's patients. The method used to create and use the algorithm is explained. The findings demonstrate the beneficial effects of using the algorithm. The paper concludes with the recommendation that algorithms should be more widely used for better treatment outcomes.

Topics: Algorithms; Anemia; Clinical Protocols; Drug Administration Schedule; Drug Monitoring; Drug Prescriptions; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Medical Order Entry Systems; Medical Records Systems, Computerized; Nurse Clinicians; Nurse's Role; Nursing Assessment; Nursing Audit; Nursing Evaluation Research; Professional Autonomy; Recombinant Proteins; Registries; Renal Dialysis; Time Factors; United Kingdom

Epoetin alpha is known to produce a hematological response in anemic cancer patients. A concomitant reduction in fatigue as well as an improvement of depression and anxiety and of quality of life has been reported. However, these effects are discussed controversially. Psychological variables may have a moderating effect on fatigue reduction.. Fifty-four anemic cancer outpatients were treated with epoetin alpha over 26 weeks with an initial dose of 3 x 10,000 IU/week and further individually adapted dosage. Hemoglobin level, fatigue, depression, anxiety, and health-related quality of life were measured every 4 weeks.. The hematological response rate was 50%, with 1/3 occurring after more than 8 weeks of treatment. Fatigue, depression, and quality of life improved significantly. Reduction in fatigue was associated with response, but the correlations between fatigue and hemoglobin were weak. Less depression and higher quality of life before treatment correlated with a better fatigue reduction when controlling for hemoglobin increase and initial fatigue level.. Psychological variables influence the reduction of fatigue during therapy with epoetin alpha in anemic cancer patients and should therefore be assessed at the beginning of treatment.

Topics: Adult; Aged; Anemia; Anxiety; Biomarkers; Case-Control Studies; Depression; Epoetin Alfa; Erythropoietin; Fatigue; Female; Germany; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Predictive Value of Tests; Psychology; Quality of Life; Recombinant Proteins; Surveys and Questionnaires; Time Factors; Treatment Outcome

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Observation; Prognosis; Randomized Controlled Trials as Topic; Recombinant Proteins

Patients with failed renal transplants represent an increasing proportion of the current dialysis population. Although their risk of anemia might be expected to be high, whether these patients receive adequate anemia therapy after returning to dialysis is unknown. We studied intravenous iron use, epoetin doses, and hemoglobin levels in patients with and without failed renal transplants who survived for 6 months after initiation of dialysis in the United States between 1996 and 2001. Of the study population (n=220 557), 9922 (4.5%) had failed renal transplants. In spite of a greater likelihood of receiving intravenous iron therapy (adjusted odds ratio (AOR) 1.47, P<0.0001) and epoetin (AOR 1.57, P<0.0001), patients with failed transplants were more anemic and had higher epoetin doses in each month of follow-up. During month 6, patients with failed transplants were more likely to have hemoglobin levels below 11 g/dl (AOR 1.50, P<0.0001) and to have epoetin-to-hemoglobin ratios above the population median of 1030 U/week per g/dl (AOR 1.73, P<0.0001). Patients who return to dialysis with failed transplants are at a higher risk of anemia than other patients who start dialysis; the pattern of lower hemoglobin levels and higher ratios of epoetin-to-hemoglobin suggests that relative epoetin resistance may be contributory.

Topics: Adolescent; Adult; Anemia; Epoetin Alfa; Erythropoietin; Graft Rejection; Hemoglobins; Humans; Kidney Diseases; Kidney Transplantation; Middle Aged; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Recombinant epoetin alfa and darbepoetin alfa (r-HuEPO) have been shown to be safe and effective treatments for anemia, but recent reports have suggested an increased risk of thromboembolic events when these agents are used to treat chemotherapy-induced anemia among patients with breast or ovarian cancer. We examined the possible risk of such events among patients with ovarian or primary peritoneal carcinomas and chemotherapy-induced anemia.. We retrospectively analyzed data over 10 years from women at one hospital with ovarian or primary peritoneal carcinoma and chemotherapy-induced anemia. The incidence and odds ratio for development of deep venous thrombosis, unadjusted and adjusted for baseline differences and risk factors, was assessed between patients who had received r-HuEPO versus no treatment for anemia.. Of the 364 women, 90 had received r-HuEPO and 253 had not. The incidence of deep venous thrombosis was 6.7% in the group that had received r-HuEPO and 5.1% in the group that had not (unadjusted odds ratio, 1.31; 95% confidence interval [CI], 0.48-3.55). After adjustment for differences in age, body-mass index, prior thromboembolic disease or cancer, and tobacco use, the odds ratio for developing deep venous thrombosis with the use of r-HuEPO was 1.35 (95% CI, 0.49-3.75).. The use of r-HuEPO was not associated with an increased risk of deep venous thrombosis in this population. A randomized trial is needed to further explore this issue and to detail the safety and efficacy of these agents in patients with various other cancers.

Topics: Aged; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Recombinant Proteins; Venous Thrombosis

To assess the cost-effectiveness and the budget impact of a Blood Saving Program (BSP) in patients older than 65 undergoing perthrocanteric hip fracture surgery.. Two groups of patients with perthrocanteric fracture were included. Group 1: patients not receiving treatment for perisurgical anaemia or treated with oral iron; Group 2: patients included in a BSP (treatment with endovenous iron sucrose and alfa epoetin, plus restrictive transfusional criteria). Effectiveness issues were: transfusion rate and number of red blood cell units transfused, length of postoperative stay and infection rate. Treatment cost was calculated using drug and transfused red blood cell unit prizes in 2003. We calculated potential patient population according to 2003 data.. 144 patients were included, 43 of which were in the BSP. Both groups were comparable in gender, age, preoperative length of stay, ASA and haemoglobin level at admission. Patients included in the BSP were less transfused and had less infections but postoperative stay was similar in both groups. The budget impact was 239,148 euros 95% [confidence interval (CI) 202,312-311,980] at group 1 and 311,980 euros [95% CI 275,288-348,672] at the BSP group. Including the whole potential population in the BSP (during one year 400 patients) would mean a cost increase of 72,832 euros, avoiding transfusion in 92 patients, infection in 70 patients, and saving 328 red blood cell units.. The cost increase due to endovenous iron sucrose and alfa-epoetin can be considered affordable for the hospital budget. BSP provides lower transfusion and infection rates and saves red blood cell units, compared to the standard procedure. Differences in postoperative stay should be analyzed in further larger and prospective studies including more patients.

Topics: Administration, Oral; Age Factors; Aged, 80 and over; Anemia; Budgets; Confidence Intervals; Cost-Benefit Analysis; Costs and Cost Analysis; Data Interpretation, Statistical; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Hip Fractures; Humans; Iron; Length of Stay; Male; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Risk Assessment; Treatment Outcome

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Bone Marrow; Child; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins

Topics: Anemia; Darbepoetin alfa; Data Interpretation, Statistical; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Insufficiency, Chronic

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Iron; Oxidative Stress; Recombinant Proteins; Renal Insufficiency, Chronic

Topics: Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Recombinant Proteins; Renal Insufficiency, Chronic

Topics: Anemia; Cardiovascular Diseases; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Recombinant Proteins; Renal Insufficiency, Chronic

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Recombinant Proteins; Renal Insufficiency, Chronic

Topics: Anemia; Cardiovascular Diseases; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Insufficiency, Chronic; Thromboembolism

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Databases, Factual; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Research Design; Treatment Outcome

To determine whether there is a change in the dose of epoetin alfa when switching from subcutaneous (SC) to intravenous (IV) administration in Australian haemodialysis patients.. Validated data from 2214 haemodialysis patients at 16 Australian hospitals who switched from SC to IV administration of epoetin alfa from January 2002 to September 2003 were extracted from the Renal Anaemia Management database provided by Janssen-Cilag. Of these patients, 806 had dosing data for at least 1 month before switch through to 6 months post switch (6 month cohort).. In the 6 month cohort, the mean dose was 10 776 IU/week (95% CI: 10 235, 11 317) at switch compared with 12 008 IU/week (95% CI: 11 447, 12 569) 6 months post switch, an increase in a dose of 1232 IU/week (95% CI: 868, 1596). The mean haemoglobin levels at switch were 11.55 g/dL (95% CI: 11.45, 11.66) compared with 11.59 g/dL (95% CI: 11.49, 11.68) 6 months after switch. Centre and dosing frequency of epoetin alfa before switch were determinants of increased dose.. Changing from SC to IV administration of epoetin alfa resulted in an 11% increase in mean dose to maintain haemoglobin levels in Australian haemodialysis patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Australia; Child; Cohort Studies; Databases, Factual; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Ferritins; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Transferrin; Treatment Outcome

The purpose of the present study was to determine whether Australian haemodialysis patients receiving intravenous epoetin alfa are comparable to those receiving darbepoetin alfa with respect to a range of demographic and clinical characteristics.. Data on haemodialysis patients were extracted from the Renal Anaemia Management database for the period from July 2003 to March 2004.. Patients on haemodialysis were more likely to receive epoetin alfa than to receive darbepoetin alfa (n = 1898 vs n = 603, respectively). Patients receiving epoetin alfa were marginally older than patients receiving darbepoetin alfa (61 +/- 15 vs 59 +/- 15, mean +/- SD; P < 0.05). Patients were similar in terms of proportion of males, incidence of diabetes, and angiotensin-converting enzyme inhibitor and antihypertensive use. However, patients receiving epoetin alfa had higher haemoglobin (116 +/- 13 g/L vs 113 +/- 15 g/L), serum ferritin (582 +/- 414 mug/L vs 461 +/- 350 mug/L) and transferrin saturation levels (29 +/- 13% vs 26 +/- 14%), and better dialysis adequacy test results, as measured by urea reduction ratio (URR) or Kt/V, than patients on darbepoetin alfa (P < 0.001 in all cases). The frequency of dosing was higher in the epoetin alfa group (1.7 +/- 0.7 doses/week vs 1.0 +/- 0.4 doses/week, P < 0.001). Using the 240:1 dose ratio recommended in the Australian prescribing information for darbepoetin alfa, epoetin alfa was administered at a lower dose compared with darbepoetin alfa (164 +/- 116 IU/kg per week vs 192 +/- 152 IU/kg per week, P < 0.001).. This cross-sectional sample of Australian clinical practice suggests that there are differences in the haematological parameters of patients receiving epoetin alfa compared with patients receiving darbepoetin alfa.

Topics: Adult; Aged; Anemia; Australia; Cohort Studies; Cross-Sectional Studies; Darbepoetin alfa; Databases, Factual; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Transferrin; Treatment Outcome

Epoetin therapy for dialysis-related anemia is the single largest Medicare drug expenditure. The type of facility (profit, chain, and affiliation status) at which a patient receives dialysis might affect epoetin dosing patterns and has implications for future epoetin policies.. To examine the association between dialysis facility ownership and the dose of epoetin administered.. Data from the US Renal Data System were used to identify 159,522 adult Medicare-eligible, end-stage renal disease patients receiving in-center hemodialysis during November and December 2004. Regression models were used to estimate the mean epoetin dose and dose adjustment by profit, chain, and affiliation status.. Weekly mean epoetin dose administered in December 2004 and the adjustment in dose between November and December 2004.. Compared with patients in nonprofit dialysis facilities (n = 28,199), patients in large for-profit dialysis chain facilities (n = 106,116) were consistently administered the highest doses of epoetin regardless of anemia status. Compared with nonprofit facilities, for-profit facilities administered, on average, an additional 3306 U/wk of epoetin. Among the 6 large chain facilities with a similar patient case-mix, the average dose of epoetin ranged from 17,832 U/wk at chain 5 (nonprofit facilities with a mean hematocrit level of 34.6%) to 24,986 U/wk at chain 2 (for-profit facilities with a mean hematocrit level of 36.5%). Dosing adjustments also differed by type of facility. On average, compared with nonprofit facilities, for-profit facilities increased epoetin doses 3-fold for patients with hematocrit levels of less 33% and also increased the doses among patients with hematocrit levels in the recommended target of 33% to 36%, especially in the largest for-profit chain facilities. The greatest difference in dosing practice patterns between facilities was found among patients with hematocrit levels of less than 33%.. Dialysis facility organizational status and ownership are associated with variation in epoetin dosing in the United States. Different epoetin dosing patterns suggest that large for-profit chain facilities used larger dose adjustments and targeted higher hematocrit levels.

Topics: Adult; Aged; Ambulatory Care Facilities; Anemia; Drug Utilization; Epoetin Alfa; Erythropoietin; Female; Health Facilities, Proprietary; Hematinics; Hematocrit; Humans; Male; Medicare; Middle Aged; Organizations, Nonprofit; Ownership; Private Sector; Recombinant Proteins; Renal Dialysis; United States

Topics: Ambulatory Care Facilities; Anemia; Drug Utilization; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Ownership; Recombinant Proteins; Renal Dialysis; United States

To determine the prevalence of anemia in an outpatient heart failure clinic, describe the type of anemia in patients treated there, and evaluate the potential costs associated with epoetin therapy in this cohort.. Single-center, retrospective cohort analysis (part 1) and a literature-based economic decision analysis (part 2).. Medical records from a multidisciplinary, outpatient, heart failure clinic, and published hospitalization and drug-use data.. We evaluated 170 adults with chronic heart failure who were enrolled in the clinic and for whom at least one complete blood count was recorded between January 1, 2003, and April 15, 2006.. In part 1, demographic and clinical data were extracted from electronic medical records. The overall prevalence of anemia was 47.6% or 47.1%, as based on World Health Organization or National Kidney Foundation definitions, respectively. Normocytic anemia was characterized in 75.0% of patients. In part 2, heart failure hospitalization rates and costs, drug acquisition, and drug administration were estimated by using the published literature. In a hypothetical cohort of 100 patients with heart failure and comorbid anemia, the costs associated with outpatient epoetin and intravenous iron therapy exceeded savings in hospitalization costs by $83,070. Results of 1-way sensitivity analyses generally confirmed robustness of the model.. Anemia is a common comorbidity in patients with chronic heart failure treated in the outpatient clinic. Although the current evidence is insufficient to support the use of epoetin in this population, initial findings indicate that epoetin and intravenous iron therapy may be associated with positive clinical outcomes. From a pharmacoeconomic standpoint, however, a reduction in the cost of heart failure-related hospitalization does not offset the cost of epoetin and intravenous iron therapy.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care Facilities; Anemia; Cardiac Output, Low; Chronic Disease; Cohort Studies; Cost-Benefit Analysis; Costs and Cost Analysis; Decision Support Techniques; Epoetin Alfa; Erythropoietin; Female; Health Care Costs; Hematinics; Hospitalization; Humans; Iron; Male; Middle Aged; Prevalence; Recombinant Proteins; Retrospective Studies

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Safety; Survival Analysis

Anemia is one of most common complications in end stage renal disease (ESRD) patients. Erythropoietin has been recommended for treatment of anemia in these patients.. To evaluate the clinical efficacy, safety and usefulness of newly imported erythropoietin, called Espogen, usage in ESRD undergoing hemodialysis.. An open, non-comparative, prospective study of administered Espogen was conducted in 30 ESRD patients undergoing hemodialysis for a 12 week period. Eligible criteria included hemoglobin of less than 8 g%, hematocrit of less than 25% for at least three consecutive months with a serum ferritin of more than 100 ng%. Initial dose of drug was 150 units/kg/week subcutaneously, two or three times a week and dosage was adjusted to maintain the Hb at 10-12g%.. In 28 patients, hemoglobin and hematocrit were increased significantly from 7.1 +/- 1.14 g/dl and 22.1 +/- 3.24% at baseline to 10.1 +/- 1.49 g/dl and 31.7 +/- 4.01% at the end of the study period respectively (p < 0.05). Mean weekly of Espogen dosage was 8390 +/- 2452.7 IU/week, which was 152.1 IU/kg/week. Some patients could reduce the dose at week 10. Reticulocyte increased significantly from 0.69 +/- 0.58% at baseline to highest value, 1.41 +/- 0.74 at 2 week and 1.30 +/- 0.66 at the end of the present study. Serum vitamin B12, serum folate, and red blood cell folate were not significantly changed. However serum ferritin decreased significantly from 840.6 +/- 948.95 to 582.7 +/- 990.70 ng/ml (p < 0.05). General condition including SF-36 score and tiredness were improved. There were no significant adverse events except mean arterial blood pressure of pre dialysis value which was statistically significant increased at the end of the present study (from 101.0 +/- 17.65 at week 0 and 110.4 +/- 16.8 mmHg at week 12, p = 0.0223).. This clinical study showed that Espogen has proven effective and safe for treatment of anemia in hemodialysis patients. No serious adverse events occurred during the study period.

Topics: Anemia; Blood Pressure; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Topics: Advisory Committees; Anemia; Darbepoetin alfa; Drug and Narcotic Control; Drug Labeling; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Risk; Stimulation, Chemical; Thromboembolism; United States; United States Food and Drug Administration

Topics: Advisory Committees; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Health Expenditures; Hematinics; Humans; Insurance Coverage; Medicare; Neoplasms; Recombinant Proteins; United States; United States Food and Drug Administration

Blood management strategies is a term used to address a coordinated approach to the management of blood loss in the perioperative period for total joint arthroplasty. The premise of any blood management strategy is that each patient, surgeon, and operative intervention experiences different risks of requiring transfusion, that those risks can be identified, and that a plan can be implemented to address them. A surgeon's decision to transfuse should be based on physiologic assessment of the patient's response to anemia and not on an arbitrary number ("transfusion trigger"). Intervention strategies can be applied preoperatively, intraoperatively, and postoperatively. Patient-specific planning allows for the appropriate use of patient, hospital, and system resources, ensuring that the consequences of anemia are minimized and that the patient's recovery process is optimized.

Topics: Anemia; Arthroplasty, Replacement; Blood Loss, Surgical; Blood Transfusion, Autologous; Disease Management; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Intraoperative Period; Postoperative Period; Recombinant Proteins

Topics: Anemia; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Humans; Recombinant Proteins; Reverse Transcriptase Inhibitors; United States; United States Food and Drug Administration; Zidovudine

The National Kidney Foundation (NKF) clinical practice recommendations for treating anemia in chronic kidney disease (CKD) and the dosing, route and frequency of administration, efficacy, and safety of currently available and investigational drug therapies for anemia in patients with CKD, including the erythropoietin-stimulating agents (ESAs) iron replacement, and adjuvants, are described.. The NKF recommendations for ESA use are general and include dosing based on the measured and target hemoglobin concentrations, the rate of increase in hemoglobin, and clinical circumstances, with the route and frequency of administration determined by the CKD stage, treatment setting, efficacy, and ESA class. A serum ferritin concentration of 100-500 ng/mL is the target during oral and intravenous (i.v.) iron therapy for predialysis and peritoneal dialysis patients, but use of the i.v. route of administration and a target serum ferritin concentration of 200-500 ng/mL is recommended for hemodialysis patients by NKF. Iron deficiency and inflammation are possible causes of inadequate response to ESAs. The safety profile of epoetin alfa and darbepoetin alfa are similar, but the longer half-life of darbepoetin alfa permits administration on a once-monthly basis in patients with CKD and anemia. Extended dosing of CERA also appears safe and effective in dialysis patients with CKD. Several investigational anemia therapies with a variety of mechanisms of action are in development.. Efforts by the NKF to update their clinical practice recommendations provide clinicians with insight into the optimal therapeutic approach to treating anemia in patients with CKD. Clinical research has resulted in the development of new therapeutic modalities to improve outcomes in patients with CKD and anemia.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Ferritins; Hematinics; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis

Treatment of anemia in hemodialysis patients usually requires the use of expensive erythropoietic proteins. Cost analyses usually focus on drug acquisition costs. Other costs associated with anemia therapy include resources for anemia monitoring as well as preparation and administration of an erythropoiesis-stimulating agent.. The nonacquisition costs associated with subcutaneous administration of epoetin alfa were determined in a Canadian hemodialysis unit. A time-and-motion technique was used to determine the nursing time for preparation and administration. Fixed anemia costs were inventory control, monitoring, blood sampling, and laboratory analysis. Variable costs were those which varied with dosing frequency. The costs are expressed in Canadian dollars (2005).. The mean time associated with preparation and administration was 3.2 min/injection. The annual nonacquisition per patient cost was CAD 2,290.04. Fixed costs were CAD 1,946.01, while the variable costs were CAD 344.03/year. Sensitivity analysis showed a decrease in cost to CAD 1,611.34, if iron monitoring were decreased from monthly to 3 monthly, and to CAD 2,090.66, if patients were converted to less frequent dosing using darbepoetin alfa.. The nonacquisition costs associated with anemia therapy in hemodialysis patients are considerable. Less frequent monitoring of iron therapy and less frequent dosing could decrease costs by CAD 678.40 and CAD 199.38/patient/year, respectively.

Topics: Anemia; Comorbidity; Epoetin Alfa; Erythropoietin; Health Care Costs; Humans; Kidney Failure, Chronic; Models, Economic; Ontario; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Heart Valve Prosthesis Implantation; Hematinics; Humans; Middle Aged; Mitral Valve Stenosis; Postoperative Complications; Preoperative Care; Recombinant Proteins; Risk Factors; Treatment Outcome

Topics: Anemia; Centers for Medicare and Medicaid Services, U.S.; Conflict of Interest; Darbepoetin alfa; Drug Industry; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Medical Oncology; Medicare; Neoplasms; Nephrology; Product Surveillance, Postmarketing; Recombinant Proteins; United States; United States Food and Drug Administration

Anemia of critical illness is common among intensive care unit patients. A blood management pilot program was initiated to study the pharmacodynamic response of epoetin alfa in critically ill patients and assess the impact of the use of a standardized order set of pharmaceuticals, including epoetin alfa and intravenous iron sucrose, on the quantity of red blood cell units transfused in the adult intensive care unit.. A pre-printed order set was developed which included baseline and follow-up laboratory monitoring and pharmaceutical options for iron, either intravenous and/or oral, folic acid, ascorbic acid, cyancobalamin, and weight-based epoietin alfa. Laboratory studies included: hemoglobin/hematocrit, reticulocyte count, absolute reticulocyte count, immature reticulocyte fraction obtained at baseline, and on day three and day five; in addition, iron, total iron binding capacity, transferrin saturation, and ferritin were obtained at baseline and on day five. An average hemoglobin response of 0.8 g/dL five days after administration of epoetin alfa was demonstrated in a diverse population of critically ill patients. Patients who received intravenous iron did not have a difference in mortality as compared to those patients who did not receive intravenous iron; however, there was a significantly longer length of stay. The cost of epoetin alfa was $64,000 over 10 months (approximately 8-10 patients/month). Transfusions of RBCs in adult intensive care unit decreased over the initial five months of the pilot study.. Use of erythropoiesis stimulating agents (ESAs) in the critically ill is controversial. Implementing a standardized approach in the pharmaceutical management of anemia in the critically ill patient is possible. Limitations with the order set and standardized protocol included errors in selection of dose/weight, incomplete laboratory/monitoring, and inconsistent prospective/concurrent review to guide therapy. The determination of the cost-effectiveness of epoetin alfa therapy in anemia of critical illness was not the purpose of this project, but will be the focus of future studies.

Topics: Adult; Aged; Anemia; Baltimore; Blood; Blood Chemical Analysis; Clinical Protocols; Critical Care; Critical Illness; Drug Costs; Drug Monitoring; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Outcome and Process Assessment, Health Care; Pilot Projects; Recombinant Proteins

Topics: Anemia; Cost Allocation; Drug Prescriptions; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Medicare; Recombinant Proteins; Reimbursement Mechanisms; Renal Dialysis; United States

Topics: Anemia; Cost Control; Drug Prescriptions; Drug Utilization; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Medical Audit; Medicare; Nephrology; Outcome Assessment, Health Care; Recombinant Proteins; Reimbursement Mechanisms; United States

There are limited data suggesting that initiation of epoetin alfa at extended dosing intervals of every 2, 3, or 4 wk may be efficacious for treating anemia in patients who have chronic kidney disease and are not on dialysis (CKD-NOD). This open-label, multicenter, single-arm study investigated the efficacy of administration of 20,000 IU of epoetin alfa once every 2 wk as initiation therapy in these patients. Adults with CKD-NOD were eligible when they had hemoglobin (Hb) <11 g/dl, GFR of 10 to 60 ml/min per 1.73 m2, and stable serum creatinine for the past 6 mo. Patients received 20,000 IU of epoetin alfa subcutaneously every 2 wk for up to 27 wk, with dosage adjustments permitted after 4 wk of treatment. The primary efficacy end point was the proportion of patients with Hb response, defined as achievement of the target Hb range of 11 to 12 g/dl for at least two consecutive visits. Sixty-seven patients were enrolled; >88% (59 of 67) of patients achieved an Hb response. Mean Hb increased to the targeted range by week 6 and remained in the range through week 28. Hb increases of 1 and 2 g/dl were observed in 91 and 78% of patients, respectively. Epoetin Alfa was well tolerated; most adverse events were mild or moderate in nature and typical of the CKD patient population. In this study, results demonstrated that epoetin alfa can be initiated safely and effectively at an extended dosing interval of 20,000 IU every 2 wk in patients with CKD-NOD.

Topics: Aged; Anemia; Chronic Disease; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Diseases; Male; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Health Resources; Hematinics; Humans; Injections; Neoplasms; Recombinant Proteins; Research Design; Time Factors; Treatment Outcome

Topics: Ambulatory Care Facilities; Anemia; Drug Utilization; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Ownership; Patient Care Team; Recombinant Proteins; Renal Dialysis; United States

Topics: Ambulatory Care Facilities; Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Hemoglobins; Humans; Ownership; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic; United States

Topics: Ambulatory Care Facilities; Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Ownership; Recombinant Proteins; Renal Dialysis

Topics: Ambulatory Care Facilities; Anemia; Epoetin Alfa; Erythropoietin; Europe; Hematinics; Humans; Ownership; Recombinant Proteins; Renal Dialysis

Topics: Ambulatory Care Facilities; Anemia; Economics, Medical; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Ownership; Recombinant Proteins; Renal Dialysis

Topics: Ambulatory Care Facilities; Anemia; Epoetin Alfa; Erythropoietin; Health Personnel; Hematinics; Humans; Ownership; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Male; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Decision Making; Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Patient Participation; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Blood Transfusion; Cost-Benefit Analysis; Critical Care; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins

The effectiveness of the erythropoietic response can be evaluated using the resistance index (RI) to erythropoietic agents (EA) that measures the relationship between the dose administered and the hemoglobin levels attained. In a hemodialysis population, the RI is associated with several clinical and biochemical parameters, such as albumin levels, C-reactive protein (CRP), body mass index (BMI) and Kt/V. This index therefore reflects an important group of parameters that indicate comorbidities and measures the effectiveness of the treatment received. A substantial proportion of chronic hemodialysis patients show a relative resistance to human recombinant erythropoietin (rHuEPO) and require high doses to reach hemoglobin levels above 11 g/dl. Darbepoetin alpha is a new erythropoietic agent with a longer half-life than rHuEPO and greater biological activity in vivo. Furthermore, it remains at clinically effective plasma levels for much longer than rHuEPO. This study evaluated the effect on RI of switching from epoetin alpha to darbepoetin alpha in hemodialysis patients requiring i.v. rHuEPO at either high ( >10,000 UI/w) or low ( <4,000 UI/w) doses, compared to a control group receiving epoetin alpha. Unlike the control group, both groups of patients who switched to darbepoetin alpha showed a reduction in RI and a progressive reduction in the dose required of darbepoetin alpha with respect to the equivalent dose at treatment conversion. In the group requiring high doses, darbepoetin alpha RI (DRI) at week 24 was a significant 23.9% lower than epoetin alpha RI (ERI) at conversion (week 0) (p <0.01). In the group requiring low doses, DRI at week 24 was 13.4% lower than the ERI at conversion (p = NS). In both control groups, ERI at week 24 was higher than ERI at week 0. All groups showed stable hemoglobin levels across the study, with mean levels between 11.5 and 13.3 g/dl. CRP at week 24 was significantly related to albumin levels (p <0.001). In conclusion, switching hemodialysis patients from epoetin alpha to darbepoetin alpha was associated with a significant improvement in RI in the group of patients with high doses of EA, which we consider to be an important indicator of the effectiveness and quality of the treatment administered.

Topics: Adult; Aged; Anemia; C-Reactive Protein; Cohort Studies; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

The inpatient dosing patterns and treatment costs in cancer and predialysis chronic kidney disease (CKD) patients treated with erythropoietic agents from a hospital pharmacy perspective were studied.. An analysis of electronic inpatient records from the Premier Perspective comparative hospital database was conducted. Study participants were identified through hospitalizations recorded between July 2002 and March 2005 from over 500 hospitals nationwide. Adult patients with an admitting diagnosis of cancer or predialysis CKD and treated with epoetin alfa or darbepoetin alfa during hospitalization were included. Patients who had received renal dialysis or both agents during a hospitalization were excluded. Wholesale acquisition costs from September 2006 were used to calculate drug costs.. A total of 25,645 hospitalized patients with cancer (22,873 received epoetin alfa; 2,772 received darbepoetin alfa) and 66,822 hospitalized patients with CKD (60,079 received epoetin alfa; 6,743 received darbepoetin alfa) were identified. The mean cumulative dose per hospitalization resulted in dose ratios of 245:1 and 242:1 (units epoetin alfa:micrograms darbepoetin alfa) for cancer and CKD patients, respectively. On the basis of the cumulative dose per hospitalization, drug costs for darbepoetin alfa-treated patients were approximately 50% higher than drug costs for epoetin alfa-treated patients for both oncology and CKD patients.. Epoetin alfa was associated with less cost compared with darbepoetin alfa for treating inpatients with cancer or CKD. Further research including the patients' clinical outcomes is necessary to determine the true pharmacoeconomic differences between the two agents.

Topics: Adult; Aged; Anemia; Cohort Studies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Health Care Costs; Humans; Inpatients; Kidney Diseases; Male; Middle Aged; Neoplasms; Pharmacy Service, Hospital; Recombinant Proteins; Retrospective Studies

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

In several studies, hemodialysis (HD) patients treated with recombinant human erythropoietin (rHuEPO) because of renal anemia showed increased levels of soluble adhesion molecules. The purpose of the study was to investigate the changes of soluble P-selectin (sSELP) and its relationship to platelet activation during a single HD session in patients with long-term rHuEPO treatment. Fifty-two HD patients with chronic renal failure were involved--26 with rHuEPO treatment (EPO group) and 26 without (non-EPO group). Thirty healthy subjects served as the control group. The sSELP, beta-thromboglobulin, and platelet factor 4 plasma levels were measured before and after a single 4-hour HD session on a cuprophane dialyzer. The basal beta-thromboglobulin and platelet factor 4 plasma levels were significantly increased in both HD groups compared with healthy controls but did not change after a single HD session, except for a significant decrease of platelet factor 4 in the non-EPO group. The predialysis sSELP plasma levels did not differ significantly compared with those of the healthy controls, but there was a significant increase of sSELP levels after a single HD session in both groups (EPO, P < .005; non-EPO, P < .05, respectively). These results suppose that the increased sSELP level was released from platelets during the course of a single HD session. The more significant increase of the sSELP plasma levels in EPO group during HD indicates that platelets are more activated in patients with long-term rHuEPO treatment, and this fact could partially explain the suspected tendency for thrombosis in these patients.

Topics: Adolescent; Adult; Aged; Anemia; Case-Control Studies; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; P-Selectin; Platelet Activation; Recombinant Proteins; Renal Dialysis; Solubility

While hospitalization is common for hemodialysis patients, perihospitalization associations between hemoglobin levels and epoetin doses are not well characterized. U.S. Medicare claims were used to identify 71,360 hemodialysis patients hospitalized from 1998 to 2003. Hemoglobin levels, epoetin doses, and epoetin responsiveness index (ERI) were compared by calendar year. In the prehospitalization month, the mean hemoglobin levels increased from 10.96 g/dL in 1998 to 11.76 in 2003 and the mean epoetin doses from 63,715 to 75,012 U; corresponding values in the hospitalization month were 10.53 and 11.19 g/dL, and 66,623 and 80,569 U. In each year, prehospitalization hemoglobin levels were achieved within 2 months, but ERI declined to prehospitalization levels within 12 months only in 2000. With mixed models, hemoglobin declines in the 3 prehospitalization months grew between 1998 (-0.1362 g/dL/month) and 2003 (-0.2003 g/dL/month). Epoetin responsiveness index slopes were J-shaped, with values of 287.9, 221.1, and 356.5U/month per g/dL in 1998, 2000, and 2003. In the 3 postadmission months, a modest increase in the rapidity of hemoglobin recovery was seen (+0.2538 g/dL/month in 1998, +0.2743 in 2003), with increasing rates of ERI change (+8.7 U/month/g/dL in 1998, +146.8 in 2003). While time to recovery of prehospitalization hemoglobin levels remained constant year to year, epoetin doses and ERI did not, suggesting that optimum perihospitalization anemia management practices have yet to be determined.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Child; Child, Preschool; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Hospitalization; Humans; Infant; Infant, Newborn; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Renal Replacement Therapy; Treatment Outcome; United States

Thrombotic events are infrequently observed in erythropoietin treatments for the anemia in tumorous patients with chemotherapy. The manufacturers call attention to this possible side effect of all kind of such drugs.. To estimate the amount of thrombotic events in erythropoietin administrations during epoetin treatments for ovarian cancer patients treated with antineoplastic drugs.. 275 ovarian cancer patients were treated with erythropoietin in the Gynecologic Department at the National Institute of Oncology, Budapest, in the period between 2000 and 2006: 52 of them were given epoetin-alfa, 157 of them epoetin-beta and 66 of the patients received darbepoetin-alfa. Median age of the patients was 60 (ranges 22 and 84) years.. Thrombotic events were detected in 3 patients out of the 275: one with epoetin-alfa and two times with epoetin-beta treatment (3/275 = 1,1%). No definite causal relationship was confirmed between the thrombotic events and the erythropoietin drugs.. Thrombosis was infrequently monitored among the authors' patients similarly to the literature data.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Humans; Hungary; Incidence; Middle Aged; Ovarian Neoplasms; Recombinant Proteins; Retrospective Studies; Thrombosis

After liver transplantation, reinfection of the newly engrafted liver with hepatitis C virus is essentially universal in patients who are viremic at the time of transplantation. Treatment with interferon preparations with or without ribavirin is recommended in patients with marked histologic injury; however, hematologic toxicity associated with therapy has been reported, which is usually treated with growth factor support, including erythropoietin analogues. We present the first reported case of anti-erythropoietin antibody-mediated pure red cell aplasia arising in the setting of hepatitis C virus therapy in a patient who underwent living donor liver transplantation.

Topics: Anemia; Antibodies; Antiviral Agents; Epoetin Alfa; Erythropoietin; Graft Rejection; Hematinics; Hepatitis C; Humans; Immunocompromised Host; Immunosuppressive Agents; Interferon alpha-2; Interferon-alpha; Liver Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Polyethylene Glycols; Prednisone; Recombinant Proteins; Red-Cell Aplasia, Pure; Ribavirin; Secondary Prevention; Tacrolimus

Anemia is a common complication of chronic kidney disease (CKD). The approved dosing interval for currently available erythropoiesis-stimulating agents (ESAs) is 2 to 3 times weekly for epoetin alfa (EPO) and every 1 to 2 weeks for darbepoetin alfa (DARB). However, clinicians sometimes use less frequent dosing in the interest of convenience.. This study investigated patterns of actual ESA use (doses and dosing intervals) and hemoglo- bin (Hb) control in adult outpatients with CKD not requiring dialysis at the Cleveland Clinic Foundation anemia clinic. The distribution of and variability in Hb levels in these patients were also examined.. The clinical charts and electronic records of adult outpatients with CKD who initiated ESA therapy before March 2005 were reviewed to identify the initial, dominant (used for the longest consecutive period), and final dosing intervals and mean weekly doses of EPO and DARB. Hb control was examined in terms of maximum deviations >12 g/dL and <11 g/dL, and the proportions of measurements outside these values.. The analysis included data from 111 outpatients (mean [SD] age, 65.9 [14.4] years; 53.2% male; 66.7% white, 29.7% black, 2.7% other, 0.9% unknown ethnicity). Twenty-one patients received EPO only, 74 received DARB only, and 16 switched ESAs. The mean duration of follow-up was 20.5 months. The most common initial dosing intervals were qwk for EPO (66.7%) and q2wk for DARB (90.5%). The dominant dosing intervals were q2wk in 61.9% of EPO patients and q3wk in 62.3% of DARB patients. However, 80.0% of those who received EPO q2wk and 63.2% of those who received DARB q3wk eventually returned to their initial dosing intervals. The largest proportions of Hb mea- surements <11 g/dL occurred at dominant dosing intervals of qwk for EPO and q2wk for DARB (both, 46.0%; 11 and 26 patients, respectively), whereas the largest proportions of measurements >12 g/dL occurred with EPO dosed at q2wk (44.0%; 5 patients) and DARB dosed at >q4wk (62.0%; 5 patients).. The patterns of ESA usage in adult outpatients with CKD at this center indicated that clinicians extended dosing intervals beyond those in the approved prescribing information. However, variations in Hb concentrations occurred during maintenance therapy administered at extended dosing intervals, resulting in the resumption of shorter dosing intervals in the majority of patients.

Topics: Aged; Anemia; Chronic Disease; Cohort Studies; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Diseases; Male; Recombinant Proteins; Retrospective Studies

Topics: Anemia; Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Humans; Iron; Recombinant Proteins

Anemia is common in end-stage renal disease (ESRD) patients and an important determinant for left ventricular hypertrophy (LVH) in dialysis patients. There are increasing numbers of biosimilar epoetin-alfa entering Thailand.. To conduct a prospective trial to evaluate the efficacy and safety of a biosimilar epoetin-alfa (epoetin) (Espogen) in ESRD patients receiving chronic hemodialysis complicated by anemia and to address its impact on the left ventricular mass index (LVMI) and volume index (LVVI) in these patients.. Twenty-two hemodialysis (HD) subjects were recruited from Rajavithi and Huachiew Hospitals. Inclusion criteria were chronic HD, hemoglobin (Hb) < 10 g/dL without preceding treatment (epoetin or transfusion) for 1 month. Echocardiographic baselines were obtained Epoetin-alfa was initially given 4,000 IU subcutaneously twice a week and titrated biweekly to keep the Hb range of 11 to 12 g/dL (titration period 12 weeks). Treatment continued until the end of 24 weeks. Records were made for conventional blood tests, blood pressure, amount of drugs needed to control blood pressure, and adverse events. Echocardiogram was repeated (on observer blinding) at the completion of the present study.. After 24-week of epoetin therapy, the predialysis Hb level increased significantly from 8.0 +/- 1.3 g/dL to 11.0 +/- 1.1 g/dL (p < 0.001). The mean dose of epoetin at the present study entry was 143.6 +/- 87.8 IU/kg/ week. At the present study entry, LVH was present in 86.4% of the patients. At the completion of the present study, a decrease in LVMI was observed in 50% of the patients; however, the mean LVMI change was not significantly different. Notably, there were minimal but significant changes in LVEDD (52.8 +/- 7.0 vs. 50.1 +/- 6.9 mm, p < 0.05), LVVI (86.2 +/- 25.2 vs. 75.5 +/- 19.5 mL/m2, p < 0.05) and when subjects were partitioned into tertiles of baseline LVMI, the LVVI change was confined to the highest tertile (103.7 +/- 25.2 vs. 79.6 +/- 21.9 mL/ m2, p < 0.05). The aortic root diameter also significantly decreased despite some increase in blood pressures but without significant change in number of antihypertensive agents. No serious adverse event was observed during the present study period.. The efficacy of anemia treatment and safety of the biosimilar epoetin-alfa was demonstrated in hemodialysis patients. Significant regression of LVVI and some reduction in LVMI were shown in this 24-week prospective trial.

Topics: Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Health Status Indicators; Heart Ventricles; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome; Ultrasonography

The mechanisms underlying the aggravation or development of hypertension frequently seen during treatment of renal anemia with epoetins are not fully elucidated. The aim of the present study was to investigate the effects of epoetin alfa on endothelial vasodilatory function in patients with renal anemia and in healthy subjects.. Eighteen preuremic patients with anemia (GFR 23.4 +/- 11 SD ml/min, Hb 101 +/- 8 g/l) and 10 healthy subjects underwent evaluation of endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIDV) by means of forearm blood flow (FBF) measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium nitroprusside (SNP, evaluating EIDV). These investigations were performed before and 30 min after an intravenous injection of epoetin alfa (10,000 IU). Ten healthy subjects underwent the same procedure with the exception that saline were given instead of epoetin. The patients were treated with epoetin alfa subcutaneously for 12-19 weeks and reevaluated when Hb exceeded 120 g/l.. EDV was attenuated after the epoetin injection in both renal patients and healthy subjects. This impairment persisted after anemia had been treated. EDIV and blood pressure remained constant. Saline had no effect on the variables measured.. Our results indicate that epoetin alfa impairs endothelial function in renal patients and healthy subjects which may have an impact on vascular complications.

Topics: Adult; Anemia; Blood Pressure; Endothelium, Vascular; Epoetin Alfa; Erythropoietin; Female; Forearm; Hematinics; Humans; Injections, Intravenous; Male; Recombinant Proteins; Regional Blood Flow; Vasodilation

The purpose of this initiative was to compare erythropoietin-alpha doses in hemodialysis patients who changed from subcutaneous to intravenous administration. The Manitoba Renal Program switched routes due to concern about erythropoietin-associated pure red cell aplasia.. We compared the erythropoietin-alpha dosage requirements during subcutaneous administration (3 months pre-switch) and intravenous administration (months 4-6 post-switch). We also compared: hemoglobin, transferrin saturation (Tsat%), ferritin, and percent of patients receiving intravenous iron. The same erythropoietin-alpha regimen was initially used when patients were switched.. Of the 628 patients receiving erythropoietin-alpha, the data were complete for 400. The dose increased 26% (mean +/- SD, 10,425 +/- 7,330 vs. 13,125 +/- 8,638 IU/week; p < 0.0001), despite similar hemoglobin, (mean +/- SD, 11.5 +/- 1.1g/dl (114.9 +/- 11.2 g/l) vs. 11.3 +/- 1.0 g/dl (113.5 +/- 10.4 g/l); p = 0.0450) and iron parameters (Tsat 30.9%, ferritin 464 ng/ml (microg/l) vs. Tsat 28.7%, ferritin 538 ng/ml (microg/l)). For the subgroup of 84 patients who maintained target hemoglobin (10-11 g/dl or 110-120 g/l) for both periods, the dose increased 26% (mean +/- SD, 8,393 +/- 6,242 vs. 10,589 +/- 7,049 IU/week; p < 0.0001) without a change in hemoglobin, (mean +/- SD, 11.5 +/- 0.3 g/dl (115.2 +/- 3.0 g/l) vs. 11.5 +/- 0.3 g/dl (114.9 +/- 3.3 g/l); p = 0.5789). When stratified by subcutaneous dose, patients with the lowest dose (<5,000 IU/week) demonstrated the greatest increase (89%), and those with the highest dose (>20,000 IU/week) experienced no increase (-3%).. Overall, erythropoietin-alpha doses increased by 26% when patients were converted from subcutaneous to intravenous administration.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

Chemotherapy induced anemia (CIA) commonly occurs in gynecologic oncology patients. This often leads to treatment with erythropoietic stimulating agents in order to prevent chemotherapy delays, dose modifications and transfusion of red blood cells. Our objective was to determine the subsequent transfusion rates following administration of either darbepoetin alfa or epoetin alfa.. A single institution retrospective chart review was performed utilizing patients from January 2003 to September 2004 who received either darbepoetin alfa or epoetin alfa for CIA (Hgb < or = 10.0). Data collection variables included patient demographics, cancer diagnosis, chemotherapy treatment(s), laboratory data, erythropoeisis stimulation data, and transfusions. Sample size calculations were set to detect a 20% transfusion rate difference between the two groups. Chi-square, Fisher exact test and student t tests were used for statistical analysis.. 123 patients were eligible for analysis (60 darbepoetin alfa; 62 epoetin alfa). 93% of darbepoetin alfa patients received 200 mg every other week, while 86% of epoetin alfa patients received 40,000 U weekly. The darbepoetin alfa and epoetin alfa groups were similar in respect to age, race, tumor type, histology, previous chemotherapy, number of chemotherapy agents, weeks of erythropoietic stimulation, and baseline serum levels of creatinine and hemoglobin. The mean baseline Hgb and change in Hgb was similar for each group (darbepoetin alfa = 11.2, 2.5 and epoetin alfa = 11.3, 2.3). Twenty one (35%) of the darbepoetin alfa patients received a transfusion of packed red blood cells compared to 12 (19%) of epoetin alfa patients (p = 0.05).. This retrospective analysis powered to detect differences in transfusion rates revealed a statistically significant difference in transfusion rates between darbepoetin alfa and epoetin alfa for the treatment of CIA. These data warrant a randomized prospective trial in gynecologic oncology patients with careful attention to the timing of initiation of treatment, dosing regimens, and titration of growth factor.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Genital Neoplasms, Female; Hematinics; Hemoglobins; Humans; Middle Aged; Recombinant Proteins; Retrospective Studies

Patients with cancer-related anemia have an inadequate Epo response that is further impaired by cancer treatments such as chemotherapy. Significant number of studies have demonstrated that treatment of anemia in cancer patients using recombinant human EPO(rHuEPO, epoetin alfa) significantly increases hemoglobin(Hb) levels,reduces transfusion requirements,and improves quality of life,particularly by relieving fatigue. However,the findings of several studies have raised the possibility of an adverse effect of thromboembolism. The American Society of Clinical Oncology and the American Society of Hematology developed an evidence-based clinical practice guideline for the use of epoetin in patients with cancer. In cancer patients, the risk of bleeding depends not only on the platelet count, but also on the underlying disease, in accordance with coagulation defects. The cause of thrombocytopenia must be established prior to platelet transfusion since platelet transfusions may be relatively contraindicated in certain conditions e. g., heparin-induced thrombocytopenia(HIT), and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome(TTP/HUS).

Topics: Anemia; Disseminated Intravascular Coagulation; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Neoplasms; Platelet Transfusion; Quality of Life; Recombinant Proteins; Thrombocytopenia

An anti-anemia drug may improve self-reported quality of life (QOL) partly because patients know their hemoglobin level is rising. In the absence of any published studies on this topic, the authors investigated the association between knowledge of hemoglobin levels and self-reported QOL.. The study analyzed health-related QOL (HRQOL) data from five randomized clinical trials of erythropoietic therapy in patients with cancer-related anemia. Patients were asked whether they knew their hemoglobin level and, if so, to report its value. Patients (n=1007) were grouped into three categories depending on the extent and accuracy of hemoglobin level knowledge. HRQOL scale scores were compared between categories.. Only 23.2% of patients reported knowing their hemoglobin level at the end of the study; however, the value was accurate (within 1 g/dl) in 88.0% of these patients. On five of the 11 HRQOL scales studied, there was a significant association between knowledge of hemoglobin level and HRQOL score. However, the magnitude of the mean difference between those who knew vs. those who did not know their hemoglobin was generally below scale thresholds for minimally important differences.. Patient knowledge of hemoglobin level has a modest association with some aspects of self-reported HRQOL. The magnitude of this association, where it exists, would be unlikely to explain large group differences in HRQOL reports over time, even for patients who know their hemoglobin level.

Topics: Aged; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Fatigue; Female; Health Knowledge, Attitudes, Practice; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Sickness Impact Profile

The erythropoietic-stimulating hormone, darbepoetin alfa (Aranesp; DPO; Amgen, Thousand Oaks, California) is a long-acting agent growing in popularity as the preferred anemia management agent for patients with chronic kidney disease. Use of this drug in existing patients treated with rHu-EPO (epoetin alfa; EPO) requires conversion dosing and the potential for serious alterations in previously stable and satisfactory hemoglobin levels. This study analyzed the dosing conversion recommended by Amgen to determine if the regimen resulted in stable hemoglobin values during the conversion.. Twenty-nine stable patients on hemodialysis were selected for conversion from EPO to DPO. The dose of DPO was taken from the conversion table recommended by Amgen and based upon the patient's weekly EPO dose. The mean conversion dose was 40 mcg weekly. The patients were monitored monthly with hemoglobin, hematocrit routine chemistries, and iPTH levels according to unit policy. The dose of DPO was individually titrated to maintain the hemoglobin concentrations at target levels between 11.5 gm/dL and 13.3 gm/dL. At the end of six months, there was an analysis of the data to determine if the results warranted an adjustment in the DPO dose and if so, what the adjusted dosing factor should be.. Fifty-seven percent of the patients in the study group experienced a drop in hemoglobin levels below pre-DPO baseline levels (13.1 +/- 0.6 gm/dL) by the third month. The mean hemoglobin level dropped to 11.0 +/- 1.2 gm/dL for the entire group, representing a mean 2 +/- 1.42 gm/dL reduction. Forty-five percent of patients had a 15% to 40% drop in hemoglobin (1.9 gm/dL-5.0gm/dL). By the sixth month, patients were back to baseline hemoglobin (13.2 +/- 2.0 gm/dL). The adjusted dose at this point averaged 107 mcg weekly. Statistical analysis suggested an adjustment of 48.4 mcg to each of the Amgen recommended dose conversion values.. The current Amgen recommended DPO dose regimen for conversion from EPO resulted in a drop in hemoglobin from baseline levels in 57.2% of patients, suggesting that the current conversion table may underestimate the dose. Based upon a statistical analysis, an additional 48.4 (50) mcg to each recommended dose is needed to maintain baseline levels.

Topics: Algorithms; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins

Topics: Anemia; Chronic Disease; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Diseases; Practice Guidelines as Topic; Recombinant Proteins

Topics: Adolescent; Anemia; Anti-Inflammatory Agents; Cardiomyopathies; Epoetin Alfa; Erythropoietin; Fluorescein Angiography; Humans; Injections; Laser Coagulation; Male; Methylprednisolone; Methylprednisolone Acetate; Muscular Dystrophy, Duchenne; Recombinant Proteins; Retinal Neovascularization; Vision Disorders; Vitrectomy; Vitreous Hemorrhage

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins

Cancer patients treated with chemotherapy often develop anaemia. This cross-sectional analysis examined the effect of anaemia treatment on patient and caregiver time and activities.. The analysis included 9,920 patients from 646 US outpatient oncology centres. Patients completed a survey that contained questions about travel time, total time for the visit and other impacts.. The mean time taken for a single clinic visit to receive anaemia treatment was 2.2 h. On average, patients receiving epoetin alfa required 17.6 h more than patients receiving darbepoetin alfa to complete a course of anaemia treatment. All patients in the study reported that they had to adjust at least one activity as a result of clinic visits. Older patients, women and patients from low-income areas were more likely to be accompanied during clinic visits.. Reducing the number of clinic visits needed for anaemia treatment by using darbepoetin alfa may benefit patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Caregivers; Cross-Sectional Studies; Darbepoetin alfa; Employment; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Regression Analysis; Time Factors

Topics: Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematocrit; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Survival Analysis

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Therapeutic Equivalency

Topics: Anemia; Critical Illness; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Subcutaneous; Intensive Care Units; Postoperative Hemorrhage; Recombinant Proteins; Treatment Outcome

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

In a large, 16-week, prospective study of 2,964 anemic patients with various cancers undergoing chemotherapy, once-weekly subcutaneous administration of 40,000 U of epoetin alfa,with potential escalation to 60,000 U, increased hemoglobin (Hgb) levels, decreased transfusion requirements, and improved quality of life (QOL) as assessed using the Linear Analog Scale Assessment (LASA) for energy, activity, and overall QOL and the Functional Assessment in Cancer Therapy-Anemia (FACT-An) QOL instrument. A retrospective subset analysis conducted in 244 colorectal cancer patients enrolled in the study showed statistically significant improvements from baseline to final readings in LASA energy, activity, and overall QOL and FACT-An Anemia Symptoms and Fatigue subscale scores (P < 0.02). Moreover, patients who achieved larger improvements in Hgb levels also demonstrated greater percentage improvements in QOL over baseline measurements. Mean Hgb levels increased by 1.2 g/dL after 4 weeks of treatment and by 1.6 g/dL by study end, independent of red blood cell transfusion within 28 days prior to the Hgb assessment. Hematopoietic response (Hgb level > or = 12 g/dL and/or increase in Hgb level > or = 2 g/dL, independent of transfusion) was observed in 61% of patients (139/229). Additionally, the proportion of patients receiving transfusions decreased from 17% at baseline to 4% during the final month of therapy. Epoetin alfa was well tolerated, with no evidence of unexpected adverse events. Except for significantly higher QOL scores at baseline, results for the cohort of colorectal cancer patients were similar to those for patients with other cancer types in the main study population.

Topics: Adenocarcinoma; Adult; Anemia; Antineoplastic Agents; Clinical Trials as Topic; Colorectal Neoplasms; Epoetin Alfa; Erythropoietin; Fatigue; Hemoglobins; Humans; Quality of Life; Recombinant Proteins; Retrospective Studies

To evaluate epoetin alfa (EPO) treatment of anemia in geriatric cancer patients receiving chemotherapy, a retrospective subgroup analysis was conducted of anemic cancer patients > or =65 years of age from three 16-week community-based studies of thrice-weekly (TIW) or once-weekly (QW) EPO for chemotherapy-related anemia (CRA).. Analyses were conducted on the overall geriatric population (> or =65 years) and by age subgroup (65-74, 75-84, and > or =85 years), and compared with younger patients (<65 years) for each individual study and for pooled data.. Some 3,634 geriatric patients were compared with 3,467 younger patients. From baseline to final measurement, EPO therapy significantly increased Hb by 2.0 g/dl in patients > or =65 years and 1.9 g/dl in patients <65 years (P<0.0001) and reduced transfusion utilization in both groups (P<0.006). Both age groups also had significant improvements in quality of life (QOL), measured by the 100-mm Linear Analog Assessment Scale (LASA). In younger patients, mean LASA changes were significantly greater than those in geriatric patients (P<0.05); however, QOL improvements in both age groups were clinically meaningful. There were no significant differences across geriatric age subgroups or between TIW and QW regimens for Hb change or QOL improvement. Overall hematopoietic response rate to EPO was 65.4% for patients > or =65 years and 64.7% for patients <65 years. Predictors of greater hematopoietic response (based on a pooled analysis) included lower body weight, baseline Hb, and baseline serum erythropoietin levels; better tumor response; and history of EPO dose reduction and longer time on study.. Anemic geriatric patients receiving EPO for CRA responded comparably to younger patients <65 years and should be treated similarly.

Topics: Aged; Aged, 80 and over; Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Retrospective Studies

To determine if temporary discontinuation of epoetin therapy in anemic patients with end stage renal disease (ESRD) influences their responsiveness to epoetin.. We performed a post hoc analysis of the data from two consecutive single-center randomized trials (T1 and T2) comparing the efficacy of two epoetin products (E1 and E2) in anemic patients with ESRD. The analysis included a subset of 44 patients who participated in both trials and were not receiving epoetin in the period (median, 12 months; range 5-15) between the trials due to epoetin shortage. Two co-primary outcomes were average weekly hemoglobin difference from the baseline and average weekly epoetin dose.. With adjustment for potential differences between E1 and E2, average weekly hemoglobin difference of 1.21 g/dL from the baseline was lower in T2 than that of 1.71 g/dL in T1: difference -0.49 (95% confidence interval [CI], -0.68 to -0.29; P<0.001). Average weekly epoetin dose of 107 IU/kg in T2 was higher than 96 IU/kg in T1 (ratio, 1.13; 95% CI, 1.04-1.24; P=0.009). With additional adjustment for within-subject changes in baseline covariates from T1 to T2 (baseline hemoglobin, body mass index, serum albumin, ferritin and transferrin saturation, intact parathormone, C-reactive protein, dialysis dose, and use of angiotensin converting enzyme inhibitors), hemoglobin response remained lower (adjusted difference, -0.44 g/dL; 95% CI, -0.73 to -0.16; P=0.004) and weekly epoetin dose remained higher in T2 than inT1 (adjusted ratio, 1.17; 95% CI, 1.03-1.34; P=0.016).. In patients with ESRD, responsiveness to epoetin was lower in T2 after a period of epoetin therapy discontinuation than in T1 epoetin trial. Since this could not be explained by within-subject changes in factors known to affect response to epoetin, a prolonged withdrawal of epoetin in patients with ESRD might independently contribute to a reduced responsiveness to epoetin at a later re-exposure.. ClinicalTrials.gov Identifier for T1 trial: NCT00322413.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Middle Aged; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Anaemia is a common toxicity in cancer patients and epoetins (EPOs) are now an established treatment. The economic profile of EPO treatment was assessed in patients with breast cancer treated by adjuvant-chemotherapy.. Two strategies were compared: without treatment by EPO and with the possible use of treatment by EPO (epoetin alfa) when required. The clinical effectiveness criterion was time adjusted to quality of life and economic data included only direct medical costs.. One hundred ninety-two patients were included. In the group with the strategy containing the possible use of EPO, 45.5% of patients effectively received EPO. A significant difference in the haemoglobin level profile over time was observed which provided a significant overall benefit of 0.0052 (p<10(-4)) quality-adjusted life year (QALY) associated with an extra cost of 1,615 (p<10(-4)). In the base case analysis, the cost per added QALY was estimated as 310,577 with the strategy containing the possible use of EPO.. This robust result seems to be unacceptable, but the only relevant point of discussion might be the level of acceptable incremental cost-effectiveness ratio (ICER) for a patient.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Chemotherapy, Adjuvant; Cost-Benefit Analysis; Cyclophosphamide; Doxorubicin; Epirubicin; Epoetin Alfa; Erythropoietin; Female; Fluorouracil; France; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Middle Aged; Quality of Life; Quality-Adjusted Life Years; Recombinant Proteins; Retrospective Studies; Sensitivity and Specificity; Treatment Outcome

Anaemia is aggravated by the coexistence of chronic kidney disease (CKD) in patients infected with human immunodeficiency virus (HIV). Darbepoetin alfa effectively alleviates CKD-associated anaemia with less frequent dosing than recombinant human erythropoietin (EPO). The current study aimed to determine the efficacy, safety and cost-effectiveness of darbepoetin alfa compared with erythropoietin alfa (EPO-alfa) for treatment of anaemia in HIV-infected subjects receiving haemodialysis.. An open label, single arm, prospective study of 12 haemodialysis subjects with HIV infection was conducted for a duration of 6 months after switching from intravenous (i.v.) EPO-alfa two/three times weekly to i.v. darbepoetin alfa once weekly. The primary end point was the proportion of patients maintaining haemoglobin (Hb) levels>or=11 g/dl while a weekly dose of darbepoetin alfa was a secondary end point.. Darbepoetin alfa, as effectively as EPO-alfa maintained the proportion of the subjects having Hb levels>or=11 g/dl at an average weekly dose of 40.60 microg compared with an equivalent dose of 51.84 microg for EPO-alfa. Antiretroviral therapy and HIV infection stage remained the same for each specific patient throughout the study period, including the last 6 months of EPO-alfa therapy. No difference in the incidence of adverse effects was observed after switching from EPO-alfa to darbepoietin alfa.. Lower doses of darbepoetin alfa at extended dosing interval is as safe and effective as EPO-alfa for treating anaemia, suggesting that darbepoetin alfa is a more cost-effective therapeutic alternative to EPO-alfa in the management of anaemia associated with HIV infection in subjects receiving haemodialysis.

Topics: Adult; Anemia; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; HIV Infections; Humans; Injections, Intravenous; Kidney Diseases; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

The use of erythropoietic growth factors to treat chemotherapy-induced anemia (CIA) has been increasing as clinicians become more aware of the ability of these drugs to improve the quality of life of patients with cancer. The cost associated with erythropoietic growth factor therapy makes its appropriate use a practical issue for physicians and hospitals. Clinical practice guidelines can benefit physicians by increasing practice efficiency, reducing medical errors, increasing the quality of medical care, and decreasing reimbursement problems. The American Society of Clinical Oncology and the American Society of Hematology, the European Organisation for Research and Treatment of Cancer, and the National Comprehensive Cancer Network (NCCN) have all published guidelines for using erythropoietic growth factors to treat CIA, and this article reviews and summarizes those guidelines. Of the three guidelines for the use of erythropoietic growth factors in CIA, the NCCN guidelines are based on the most recent data. Current evidence indicates that erythropoietic growth factors can increase hemoglobin levels, reduce the need for red blood cell transfusions, and improve quality of life; the effect of erythropoietic therapy on outcomes in patients with CIA is still being investigated.

Topics: Anemia; Darbepoetin alfa; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Europe; Growth Substances; Hematinics; Humans; Recombinant Proteins; United States

Cost control is becoming an increasingly important consideration for clinicians when planning how to provide the best treatment for anaemic cancer patients. Administration of erythropoiesis stimulating agents (epoetin alpha, epoetin beta and darbepoetin alpha) has become the standard of care for treatment of anaemia in cancer patients. However, only limited information is available on the economic comparability of epoetin alpha, epoetin beta and darbepoetin alpha, and thus this study was conducted to compare cost per patient of each of these agents for anaemic cancer patients.. All prescriptions of the agents over 1 year were analysed by two Austrian regional public health insurance associations and cost per patient for each agent was calculated from invoicing data. Data from the two regions were combined to obtain total mean drug costs per patient per year.. Analyses showed significantly lower costs for epoetin alpha ( 2,743.27 euros) than for darbepoetin alpha (3,627.98 euros ) or epoetin beta ( 3,292.28 euros): epoetin alpha vs. darbepoetin alpha (P < 0.0001); epoetin beta vs. darbepoetin alpha (P = 0.0001); epoetin alpha vs. epoetin beta (P = 0.0009). As costs of the three agents in Austria are identical for therapeutically equivalent doses, the higher cost of darbepoetin alpha was believed to be due mainly to longer treatment duration to target haemoglobin level.. The finding of a cost difference favouring epoetin alpha over darbepoetin alpha suggests the need for prospective randomized studies comparing efficacy and cost effectiveness of all three agents to obtain more definitive data.

Topics: Aged; Anemia; Austria; Cost Control; Darbepoetin alfa; Economics, Pharmaceutical; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Neoplasms; Recombinant Proteins

Topics: Anemia; Child; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Absorption of a physiological dose of ferrous iron was studied in 18 patients with solid malignancy receiving epoetin therapy for mild chemotherapy-associated anemia. The historical control group consisted of 25 iron replete volunteers (iron absorption 20 +/- 11% in males and 26 +/- 13% in females) and 21 patients with uncomplicated iron deficiency (iron absorption 71 +/- 19%). Iron absorption was increased in the majority of the cancer patients (iron absorption 59 +/- 35%). There were no significant differences in iron absorption between cancer patients who were iron replete or iron deficient according to current clinical practice guidelines (iron deficiency: transferrin saturation < 20% and/or serum ferritin < 100 ng/mL). Red cell iron incorporation was not disturbed in the majority (89%) of patients.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Intestinal Absorption; Iron; Male; Middle Aged; Neoplasms; Organoplatinum Compounds; Recombinant Proteins

Treatment of anemia in the perioperative period of major orthopedic surgery decreases the need for blood transfusion and improves perioperative outcomes. Use of epoetin alfa in this setting is FDA-approved and provides significant benefit to qualified and carefully chosen patients.

Topics: Anemia; Arthroplasty, Replacement; Blood Transfusion; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Postoperative Complications; Preoperative Care; Recombinant Proteins; Risk

To evaluate the relationship between hemoglobin (Hb) level and quality of life (QOL) in anemic patients with non-dialysis chronic kidney disease receiving epoetin alfa.. A post-hoc analysis using data from a multicenter, open-label, prospective study of epoetin alfa for anemia in patients with chronic kidney disease not on dialysis was conducted. The relationship between Hb and QOL was analyzed using correlation and longitudinal analyses, the latter adjusting for sample selection bias. The Linear Analog Scale Assessment (LASA) and the Kidney Disease Questionnaire (KDQ) subscales were used to measure QOL. The impact of an incremental 1 g/dL increase in Hb level on LASA and KDQ scores was determined using an incremental analysis.. A total of 1183 and 1044 patients formed the study populations for the LASA and KDQ analyses, respectively. There was a positive and significant relationship between Hb levels and QOL (p < 0.05). Using non-linear regression analysis, we characterized the sigmoid-shape of the relationship between Hb levels and QOL scores. Hemoglobin change was a statistically significant determinant of QOL improvement for both LASA and KDQ scales (p < 0.05). The model predicted that, based on a 2 unit change in Hb, the greatest incremental QOL improvement per unit of Hb increase occurred when Hb was in the range of 11 to 12 g/dL.. This study demonstrates that, beyond the well-known relationship between Hb increases and QOL improvements, the maximal incremental gain in QOL occurred when Hb reached 11 to 12 g/dL. This suggests that treating anemic patients with non-dialysis chronic kidney disease until their Hb level reaches 12 g/dL will result in the greatest QOL improvement per Hb unit increase. The analyses were conducted based on an open-label study of epoetin alfa and could be further validated using a randomized, controlled trial, comparing incremental gains in QOL associated with treatment initiation at varying levels of Hb across arms.

Topics: Aged; Anemia; Chronic Disease; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Quality of Life; Recombinant Proteins

To determine patient preference for once-weekly Epoetin alfa versus once-monthly (QM) darbepoetin alfa in patients with chronic kidney disease (CKD) not receiving dialysis.. AMPS (Aranesp Monthly Preference Study) consisted of two studies of similar design, each with a 2-week screening/baseline period, a 20-week QM darbepoetin alfa dosing period, and an 8-week follow-up period. Patients aged > or = 18 years had a nephrologist-reported diagnosis of CKD but were not receiving dialysis, and were required to have at least two hemoglobin levels within 10-12 g/dL and to have been receiving a stable dose (< 25% change) of once-weekly or once-every-other-weekly Epoetin alfa for at least 8 weeks. At week 21, patients could continue on QM darbepoetin alfa or revert back to their previous Epoetin alfa regimen. The primary analysis assessed patient preference at week 21 for QM darbepoetin alfa versus previous once-weekly Epoetin alfa.. AMPS enrolled 442 patients: 54% were female, 67% were Caucasian, and mean (SD) age was 68.3 (13.5) years. At week 21, 346 patients remained on study. Of the patients converted from once-weekly Epoetin alfa, 86% (138/161) preferred darbepoetin alfa QM, and of all patients who expressed a preference, regardless of previous Epoetin alfa dosing frequency, 96% (305/319) preferred QM darbepoetin alfa. Mean (SD) hemoglobin at week 29 of the study was similar to mean hemoglobin at baseline (for those who completed the study and were receiving QM darbepoetin alfa at week 29: 11.2 [1.1] g/dL at week 29 versus 11.4 [0.7] g/dL at baseline). QM darbepoetin alfa was well tolerated.. These data show that the majority of study patients preferred QM darbepoetin alfa to more frequent Epoetin alfa, and that QM darbepoetin alfa maintained hemoglobin levels at week 29 and was well tolerated over the study period. The single-item questionnaire could be a potential limitation of this study and further investigation with a multi-question instrument may be helpful in confirming these results.

Topics: Aged; Anemia; Clinical Trials as Topic; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Patient Satisfaction; Recombinant Proteins; Renal Insufficiency, Chronic

Topics: Anemia; Cardiac Output, Low; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Iron; Oxygen Consumption; Recombinant Proteins; Risk Factors

Epoetin alfa (EPO) and darbepoetin alfa (DARB) are erythropoietic agents indicated in the United States for the treatment of anemia in chronic kidney disease (CKD).. This study investigated dosing patterns and costs associated with the use of erythropoietic-stimulating therapy (EST) in patients with CKD not on dialysis who were newly starting EPO or DARB therapy in managed care organizations.. This was a retrospective analysis of medical claims data from >30 health plans for the period from July 2002 to February 2005. Patients were included if they were aged > or =18 years, had > or =1 claim for CKD within 90 days before the initiation of treatment, had newly started therapy with EPO or DARB, and had received > or =2 doses of treatment. If a patient was undergoing renal dialysis, data were censored 30 days before the first date of dialysis. Patients with a diagnosis of cancer or who had undergone chemotherapy were excluded from the analysis. The mean dosing interval was determined for both groups. Mean weekly doses and costs (using 2005 wholesale acquisition costs), weighted by the treatment duration, were calculated. The frequency of outpatient nephrologist visits was described and included in cost considerations.. The study population consisted of 595 patients who received EPO and 260 who received DARB. The EPO group was significantly older than the DARB group (mean age, 63.5 vs 61.2 years, respectively; P = 0.020). The proportion of women was similar between the 2 groups (51.6% and 50.4%). Use of extended dosing (> or =q2wk) was common in both groups (63.2% and 90.8%). The weighted mean weekly dose was 11,536 U for EPO and 42.5 mug for DARB. The mean number of outpatient nephrologist visits during treatment was similar between the 2 groups (3.9 and 3.5). Mean weekly costs (EST drug cost plus cost of nephrologist visits) were significantly lower for EPO compared with DARB (159 dollars vs 205 dollars; P < 0.001).. The majority of these CKD patients newly started on EST in managed care organizations received extended dosing regimens (> or =q2wk) of EPO or DARB. EPO treatment was associated with significantly lower mean weekly costs compared with DARB. The number of outpatient nephrology visits did not differ significantly between groups.

Topics: Anemia; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Health Maintenance Organizations; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Office Visits; Outpatients; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Treatment Outcome

Topics: Anemia; Cardiovascular Diseases; Epoetin Alfa; Erythropoietin; Heart Failure; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Recombinant Proteins; Renal Insufficiency, Chronic

To investigate dosing patterns and drug costs of erythropoietic agents and assess the frequency of outpatient nephrologist visits in an elderly population with pre-dialysis chronic kidney disease (pCKD) newly initiated on epoetin alfa (EPO) or darbepoetin alfa (DARB).. An analysis of medical claims from more than 30 healthcare plans covering all census regions of the US in the period July 2002 through February 2005 was conducted. Patients were included if they were > or = 65 years of age, had at least one claim for CKD within 90 days prior to the initiation of any erythropoietic agent, were newly commenced on either EPO or DARB, and had received at least two treatment doses. If a patient received renal dialysis, data were censored 30 days prior to the first date of dialysis. Patients diagnosed with cancer or those who had undergone chemotherapy were excluded from the analysis. The average dosing interval for both EPO and DARB was calculated and classified as once weekly (qw), every 2 weeks (q2w) or every 3 weeks or less frequently (> or = q3w). Weighted average weekly doses were scaled based on treatment duration. The frequency of outpatient nephrologist visits was analysed. Average weekly treatment costs were calculated and presented using the May 2005 Wholesale Acquisition Costs.. A total of 293 EPO and 102 DARB patients met the inclusion criteria. The two groups of patients had similar mean age (74.4 years for EPO vs 74.3 years for DARB) and gender distribution (47.4% female for EPO vs 51.0% for DARB). Extended dosing (every 2 weeks or less frequently: > or = q2w) during treatment was observed in both groups (EPO: qw 49.8%, q2w 31.7%, > or = q3w 18.4%; DARB: qw 19.6%, q2w 52.9%, > or = q3w 27.5%). The average dosing interval between injections was 13.6 days for the EPO group and 17.3 days for the DARB group. The weighted average weekly dose was 12,748 units for EPO and 43.5 microg for DARB. The average weekly erythropoietic treatment cost was significantly greater for DARB compared with EPO (190 US dollars vs 155 US dollars per week [2005 values]; p = 0.028). After controlling for covariates, the cost difference between the two groups was more pronounced and remained statistically significant (adjusted cost difference 41 US dollars/week higher for DARB patients; p = 0.013). The frequency of outpatient nephrologist visits during treatment was similar between the two groups (EPO 3.4 vs DARB 3.0 visits).. Based on this analysis of claims data from more than 30 US healthcare plans, extended dosing (> or = q2w) of EPO and DARB was common in elderly pCKD patients treated with erythropoietic agents, with significantly higher weekly drug costs observed in the DARB group compared with the EPO group. The number of outpatient nephrologist visits was not significantly different between EPO and DARB patients. This study was the first to evaluate the dosing patterns of EPO and DARB in elderly pCKD patients in a large managed care population.

Topics: Aged; Anemia; Cohort Studies; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Costs; Epoetin Alfa; Erythropoietin; Health Care Costs; Humans; Kidney Failure, Chronic; Managed Care Programs; Office Visits; Recombinant Proteins; Renal Dialysis; Retrospective Studies

This study set out to identify the resource use and time commitment associated with treatment of anaemia with erythropoietic therapy, for both haematology/oncology clinics and patients.. The study was carried out at three haematology/oncology clinics in the US, and included 124 cancer patients with anaemia. Stages in the administration of epoetin alfa were identified (preparation, injection and documentation). At each site a trained researcher observed medical staff and recorded the time taken for each stage, in minutes, using a stopwatch. The supplies used for each stage were also recorded. Travel times, waiting times and demographics for patients and caregivers attending the clinic were obtained from self-report questionnaires during the clinic visit. In total, 177 injections of epoetin alfa were administered.. Total mean time clinic staff and patients spent on treatment visits.. The total mean time expended by clinic staff for each injection, including preparation, administration, documentation and phlebotomy, was 25.5 minutes (range 18.6-31.2 at individual centres). The total mean time requirement for patients (time spent travelling to and from the clinic, time spent waiting for the epoetin alfa injection) was 83 minutes.. Treatments that may reduce the time burden of anaemia management should be considered.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Caregivers; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Female; Health Resources; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins; Time Factors

Topics: Anemia; Cardiovascular Diseases; Drug Industry; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Despite an increase in the use and average dose of recombinant human EPO (rh-EPO) over the last 15 years, a substantial percentage of patients still do not achieve hemoglobin targets recommended by international guidelines. The definition of rh-EPO resistance has been introduced to identify those patients in whom the target hemoglobin level is not attained despite a greater-than-usual dose of erythropoietin-stimulating agent (ESA). In recent years, increasing attention has been paid to the relationship between dialysis, increased inflammatory stimulus, malnutrition, and ESA response. About 35% to 65% of hemodialysis patients show signs of inflammation that could be a cause of anemia through the suppression of bone marrow erythropoiesis by a number of cytokines. A large proportion of chronic kidney disease patients also have protein-energy malnutrition and wasting; low serum albumin levels, together with other more specific nutritional markers, are predictors of rh-EPO response. A diminished nutritional state could then be a feature of patients who are resistant to ESA treatment, with malnutrition probably being a consequence of a chronic inflammatory state. Starting from the hypothesis that anemia, partially attributable to a reduced response to ESA, could be the link among malnutrition, inflammation, and the poor outcome of chronic kidney disease patients, we designed a multicenter observational study, the Malnutrition-Inflammation-Resistance-Treatment Outcome Study (MIRTOS), aimed at evaluating the impact and possible causes of resistance to ESA in a large sample of hemodialysis patients. We hope the results of MIRTOS will represent a step forward toward a better understanding of the factors influencing the response to ESA in hemodialysis patients.

Topics: Anemia; Chronic Disease; Darbepoetin alfa; Drug Resistance; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Inflammation; Kidney Diseases; Kidney Failure, Chronic; Malnutrition; Protein-Energy Malnutrition; Recombinant Proteins; Renal Dialysis

An evidence-based epoetin alfa protocol and a multidisciplinary blood-conservation program were implemented in a medical intensive care unit (MICU) and surgical intensive care unit (SICU).. Baseline data were collected to evaluate the use of epoetin alfa and red blood cell (RBC) transfusions in our MICU and SICU. An evidence-based protocol for epoetin alfa use and a multidisciplinary blood-conservation program were designed, approved, and implemented. Preprotocol patients consisted of a convenience sample of 18 patients receiving epoetin alfa for various indications who were admitted to our MICU and SICU from January 1 to December 31, 2002. The postprotocol sample consisted of 40 patients who received epoetin alfa for the treatment of anemia due to critical illness who were admitted to the MICU and SICU from March 25 to May 23, 2003. Postprotocol data were collected and compared with baseline data. All patients seen in the MICU and SICU, during the postprotocol period, regardless of whether they were receiving epoetin alfa, were included in the multidisciplinary blood-conservation program. Postprotocol data showed statistically significant improvements in epoetin alfa dosing and monitoring and in the use of adjunctive therapy. Pharmacist-initiated blood-conservation strategies resulted in several blood-draw reductions and discontinuations. Statistically significant reductions in the number of RBC units transfused per patient and per intensive care unit (ICU) day were also observed.. An epoetin alfa protocol and a multidisciplinary blood-conservation program contributed to rational prescribing of epoetin alfa and to a reduction in the number of RBC units transfused per patient and per ICU day.

Topics: Anemia; Blood Specimen Collection; Clinical Protocols; Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hospital Bed Capacity, 500 and over; Hospitals, University; Humans; Intensive Care Units; Male; Middle Aged; Program Development; Quality Assurance, Health Care; Recombinant Proteins

Anemia is adversely associated with poor uremia control and is an established cardiovascular risk factor in patients with end-stage renal disease (ESRD). Nocturnal home hemodialysis (NHD) is a novel form of renal replacement therapy that offers superior clearance of uremic solutes and improvements in several cardiovascular outcome parameters. We conducted a retrospective cohort study to test the hypotheses that augmenting the dose and frequency of dialysis by NHD would improve hemoglobin (Hb) concentrations and decrease requirement of erythropoietin (EPO) in ESRD patients.. In 63 patients (mean age: 46 +/- 2 years) receiving NHD (mean duration: 2.1 +/- 0.2 years), Hb, EPO dose, iron saturation, ferritin were determined before and at six monthly repeated intervals after conversion to NHD. For comparison, 32 ESRD patients (mean age: 57 +/- 3 years) who remained on self-care conventional hemodialysis (CHD) were also studied.. There were no differences in baseline Hb concentrations, iron saturation, ferritin, or EPO dose between the two cohorts. After transfer from CHD to NHD, there were significant improvements in Hb concentrations (from 115 +/- 2 to 122 +/- 3 (6 months) and 124 +/- 2 (12 months) g/l, p = 0.03) despite a fall in EPO requirement (from 10,400 +/- 1400 to 8500 +/- 1300 (6 months) and 7600 +/- 1100 (12 months) U/week, p = 0.03). In contrast, CHD cohort had no change in EPO requirement (from 8300 +/- 1100 to 8100 +/- 1300 (6 months) and 8600 +/- 1000 (12 months) U/week, p > 0.05) or Hb concentrations (from 110 +/- 2 to 115 +/- 3 (6 months) and 115 +/- 2 (12 months), p > 0.05). There was a higher percentage of ESRD patients who did not require EPO in the NHD cohort (24% vs. 9.4%, p = 0.01). Lower Hb concentrations were noted in the CHD cohort despite higher iron saturation (0.25 +/- 0.01 (NHD) vs. 0.33 +/- 0.02 (CHD), p = 0.02) at the end of follow-up.. Enhancing uremic clearance by NHD resulted in a rise in Hb and a fall in EPO requirement.

Topics: Adult; Anemia; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemodialysis, Home; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Retrospective Studies

Recent studies have suggested that epoetin treatment of anaemia may influence the survival of patients with cancer. We conducted an analysis of long-term survival in patients with lymphoproliferative malignancies treated with epoetin-beta or placebo in a large-scale study. This was a randomized, double-blind trial in which patients with transfusion-dependent anaemia and lymphoproliferative malignancy received epoetin-beta 150 IU/kg or placebo three times weekly for 16 weeks. Long-term survival data were analysed by standard Kaplan-Meier methods and differences between groups were assessed using a log-rank test. The intention-to-treat population consisted of 343 patients (epoetin-beta, n = 170; placebo, n = 173). There were no major differences between the two treatment groups in demographic or clinical characteristics/prognostic factors. A total of 110 (65%) patients died in the epoetin-beta group (censored, n = 60) and 109 (63%) died in the placebo group (censored, n = 64) up to the end of long-term follow up. Kaplan-Meier curves for survival were similar in both groups. Median survival was 17 months with epoetin-beta and 18 months with placebo. A log-rank test indicated no significant difference in survival (P = 0.76). This long-term follow up indicated that epoetin-beta has no significant effect on survival compared to placebo in anaemic patients with lymphoproliferative malignancies.

Topics: Anemia; Double-Blind Method; Epoetin Alfa; Erythropoietin; Follow-Up Studies; Hematinics; Humans; Lymphoproliferative Disorders; Proportional Hazards Models; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Rate; Treatment Failure

The European Survey of Anaemia Management 2003 (ESAM 2003) was a 1 day randomized survey conducted to assess anaemia management in dialysis patients 4 years after the introduction of the European Best Practice Guidelines. The survey included 8100 patients from 11 European countries and Israel. Overall, haemoglobin (Hb) levels > or =11.0 g/dl, as recommended by the guidelines, were achieved in 66% of patients. Only 48% of patients had adequate iron status, with transferrin saturation values missing for 27% and functional or absolute iron deficiency reported for 17 and 9%, respectively. In order to identify factors affecting epoetin dose and Hb levels, the countries were divided into two groups based on the percentage of patients with Hb levels > or =11.0 g/dl (>70% in group 1 and 60-70% in group 2). The most probable causes for better management in group 1 were administration of higher epoetin doses and better monitoring and management of iron status. In patients with Hb <11.0 g/dl, mean epoetin-alpha/beta doses were significantly lower for subcutaneous than intravenous (i.v.) administration, whereas mean doses were similar for both routes in patients with Hb > or =11.0 g/dl. When standardized for Hb levels, the dose ratio of i.v. epoetin-alpha/beta to i.v. darbepoetin alfa was 176:1 (95% confidence interval, 166:1-189:1). Limited comparisons between the eight countries that participated in ESAM 2003 and the original ESAM revealed that many patients still have haemoglobin levels below the current recommendations despite significant improvements in management of renal anaemia over the last 5 years.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Erythropoietin; Europe; Female; Health Surveys; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies

The aim of this study was to evaluate the effectiveness and the impact of once-weekly administration of epoetin alfa (Ea) on the management of anaemia and on the quality of life (QOL) of cancer patients receiving chemotherapy. Eighty cancer patients with life expectancy > or = 24 weeks and haemoglobin (Hb) levels < 10.5 g/dL were studied. After an initial screening of patients' demographic and clinical characteristics, Ea 40000 U once a week was administered over a period of 4 months. In case of patients with Hb level exceeding > 14 g/dL or in case of non-response, the dosage was reconsidered. Every month, data regarding Hb levels, clinical variations, changes in the chemotherapy regimen and transfusion use since the last study visit, were evaluated. The Linear Analogue Scale Assessment scale was used for the evaluation of the QOL. The readmissions to hospital rates (P < 0.002) and the transfusion use rates (P < 0.003) were significantly decreased comparatively with baseline. A mean increase from baseline to the final Hb level (P < 0.001) was established, as well as a significant improvement in the functional ability, energy and in the overall QOL (P < 0.001). In conclusion, the treatment of cancer patients with Ea once-weekly is effective and safe, improving their haematological parameters and QOL.

Topics: Adult; Aged; Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Treatment Outcome

In 2002, it was contraindicated the use of epoetin alfa by a subcutaneous way to avoid the risk of the pure red cell aplasia in chronic renal failure patients. This forced to change the prescription in the way it was supplied, which was especially problematic in predialysis and peritoneal dialysis, as treating out-patients, that is why it was necessary to change to epoetina beta o darbepoetin, where this contraindication was not established, in order to continue using this way. The darbepoetin has an average lifetime longer than the epoetin. Its efficacy and security have been well studied, especially in pre-dialysis and haemodialysis, but little less in peritoneal dialysis.. To evaluate our experience about the efficacy and security of darbepoetin alfa, by a subcutaneous way, in our programme of peritoneal dialysis, after the conversion of the patients previously treated with epoetin alfa.. 35 patients. 7 analytical and clinical controls are evaluated, 2 before and 5 after the conversion, with an interval of 6 weeks. Statistics methods: means +/- typical deviation, medians, distribution of frequencies, Wilcoxon test and Friedman test.. The change into darbepoetin alfa has been successful in maintaining stable haemoglobin levels in patients in peritoneal dialysis, without meaningful changes in the mean levels of haemoglobin before and after the conversion. The percentage of patients with haemoglobin in the rank 11-13 g/dl (85%) has been higher with the darbepoetin, probably due to the dose increment in the patients with previous levels of haemoglobin less than 11 g/dl. The dosages might have been widely separated (7.5 +/- 3 vs 9.2 +/- 3.2 days). The darbepoetin has been well tolerated, without any important adverse effects.. The conversion of epoetin alfa into darbepoetin alfa in peritoneal dialysis was simple, effective, secure and well tolerated.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Peritoneal Dialysis; Recombinant Proteins

Pure red cell aplasia (PRCA) is a rare, but important, complication of erythropoietin (EPO) replacement therapy in patients with renal disease. There is no consensus about the best way to treat this condition; however, recent reports indicated that immunosuppressive therapy is beneficial. We report a patient with EPO-induced PRCA treated with a regimen initially designed for antifactor VIII antibodies in patients with hemophilia. This regimen consists of immunoadsorption therapy using protein A columns, followed by oral prednisolone and single bolus infusions of intravenous immunoglobulin G and cyclophosphamide. Shortly after the course, a swift and rapid increase in reticulocyte count was evident; the patient became transfusion independent and has remained so during 2 years of follow-up. By means of this report, we wish to encourage others to consider this option when first-line treatments fail.

Topics: Anemia; Blood Transfusion; Cyclophosphamide; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Nephrosclerosis; Peritoneal Dialysis; Prednisolone; Recombinant Proteins; Red-Cell Aplasia, Pure; Remission Induction; Reticulocyte Count; Sorption Detoxification; Staphylococcal Protein A

Current guidelines give evidence-based advice on how best to manage anaemia in patients with renal disease, but these guidelines do not consider individual patient needs, so tailoring anaemia management to each patient still remains a challenge for the treating physician. Two case studies are described that illustrate some of the key factors that need to be considered. The first case emphasizes that haemoglobin (Hb) targets recommended in current guidelines may not suit all patients. The patient had been stably maintained on subcutaneous epoetin therapy with an average Hb concentration of >13.0 g/dl because he developed angina symptoms when his Hb level fell to 12.2 g/dl. Iron deficiency was identified as the likely cause of falling Hb in this patient. After the patient's iron supplementation was increased, his Hb level was normalized back to >13.0 g/dl without increasing the epoetin dose, and the angina symptoms were resolved. The second case involved a pre-dialysis patient with diabetes, who required a higher dose of epoetin after beginning concomitant antihypertensive treatment with an angiotensin-converting enzyme inhibitor. Previously, the treatment of renal anaemia in pre-dialysis patients has not been the focus of attention. Two ongoing randomized controlled trials have been designed to study early initiation of epoetin treatment in pre-dialysis patients and will provide much needed information in this area.

Topics: Aged; Anemia; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

The use of epoetin has, in Europe, been restricted to the intravenous (i.v.) route in patients on hemodialysis. This study is aimed at investigating impacts of this change in policy. We retrospectively compared 45 hemodialysis patients treated with epoetin (alpha, beta) subcutaneously (subcutaneous [s.c.] period) for 12 months before and 12 months after changing the route from s.c. to i.v., and 38 patients of the i.v. period who underwent long-term, i.v. low-dose iron therapy (i.v. iron period) for 6 months. During the study period, the dose of epoetin increased in the i.v. period compared to the s.c. period by 6.4% (7379 +/- 3556 IU/week [median 7846] vs 6907 +/- 3842 IU/week [median 5846], respectively [NS]). During the i.v. iron period, patients began to receive regular i.v. iron. The postiron epoetin dose was 5923 +/- 4779 IU/week (median 4500). The dose was decreased in comparison with the s.c. and i.v. periods by 14.2% and 19.7%, respectively. Hemoglobin decreased in the i.v. period compared to the s.c. period (120.4 +/- 8.0 g/L vs 123.5 +/- 6.7 g/L [P < 0.01]), and increased in the i.v. iron period compared to the s.c. and i.v. periods ([126.5 +/- 9.9 g/L vs 123.5 +/- 6.7 [P < 0.01]), and vs 120.4 +/- 8.0 (P < 0.01)]. Changing the route of administration of epoetin required an insignificant increase in dosage. Regular low-dose iron improves the response to epoetin and lowers the dose of epoetin, even in cases when the intravenously administration route is used.

Topics: Anemia; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Iron; Longitudinal Studies; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies

Several recently published clinical trials in anaemic patients with cancer provide convincing evidence that the quality of life of such patients is considerably impaired and that a significant improvement in quality of life can be achieved if their anaemia is corrected by treatment with recombinant erythropoietin (epoetin alfa, Eprex). Findings of some of the major studies are summarised in this issue. These summaries have been prepared to make the findings more accessible to busy clinicians who may not have time to read longer reports in specialist journals but who need to understand the important clinical implications of this research.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins; United Kingdom

Topics: Anemia; Conflict of Interest; Drug Industry; Epoetin Alfa; Erythropoietin; Hemoglobins; HIV Infections; Humans; Recombinant Proteins

The effectiveness of extended dosing of epoetin alfa beyond once-weekly (QW) has not been well explored in patients being treated for anaemia of chronic kidney disease (CKD). The current study was undertaken to assess the effectiveness of extended dosing in maintaining haemoglobin (Hb) levels in this population.. A retrospective chart review was conducted to assess the efficacy of extended epoetin alfa dosing in patients being treated for CKD-related anaemia. Eligible patients were to have received epoetin alfa once every 2 weeks (Q2W), 3 weeks (Q3W), 4 weeks (Q4W), or >Q4W administered subcutaneously for at least 3 months to maintain Hb > or = 11.0 g/dl. Patients were > or =18 years with serum creatinine 1.5 to 6.0 mg/dl for females and 2.0 to 6.0 mg/dl for males, and were not receiving renal replacement therapy. Epoetin alfa dose and dosing frequency were adjusted during treatment at the clinician's discretion. For analysis, patients were stratified into dosing groups based on their most dominant dosing regimen.. 243 patients (mean age, 71.5 years; 79% white, 54% female) who received extended epoetin alfa dosing for a mean of 10.3 months were eligible for analysis. Mean baseline estimated glomerular filtration rate and mean serum creatinine were 21.2 ml/min/1.73 m(2) and 3.1 mg/dl, respectively. Primary causes of CKD included hypertension (36%) and diabetes (28%). Most patients (82%) receiving an extended epoetin alfa regimen maintained Hb > or =11.0 g/dl. The most common dosing regimen was Q2W (51%). Mean Hb for each dosing group was maintained between 11.6 g/dl and 12.4 g/dl during the study, and glomerular filtration rate remained stable. Epoetin alfa was well tolerated across all groups.. Data from private community nephrology practices showed that extended epoetin alfa dosing effectively maintained Hb > or =11.0 g/dl in 82% of these selected patients being treated for anaemia of CKD.

Topics: Aged; Anemia; Blood Transfusion; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Glomerular Filtration Rate; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Retrospective Studies; Safety

The objective of this observational study was the early evaluation of the impact, a week after the first administration of epoetin alfa 40000 U once weekly and i.v. dose of 62.5 mg sodium ferric gluconate for seven days in improving hemoglobin levels in cancer patients affected by mild/moderate or severe anemia during chemotherapy. Twenty patients affected by solid tumors who received epoetin alfa 40000 U once weekly and daily i.v. sodium ferric gluconate for one week were evaluated: 90% of the patients showed hemoglobin increase, with a median level of hemoglobin increase of 0.73 g/L from baseline, and 50% of them showing a hemoglobin increase > 1 gr/L. The treatment was well tolerated and no adverse event was observed. The early increase of hemoglobin level from baseline is interesting and suggestive for the possibility of achieving an adequate hemoglobin level with a short-term treatment. It is still necessary to further explore the real need of iron supplementation to maintain adequate erythropoiesis prior and during epoetin therapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Dietary Supplements; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Iron; Male; Middle Aged; Neoplasms; Recombinant Proteins; Treatment Outcome

In 2002, many haemodialysis patients were switched from subcutaneous (s.c.) to intravenous (i.v.) administration of epoetin-alpha following reports of antibody formation and development of pure red-cell aplasia in patients treated via the s.c. route. We evaluated the possible effect of this change in the route of administration on haemoglobin (Hb) levels and epoetin-alpha requirements.. This retrospective survey involved 223 haemodialysis patients from 25 Swedish centres. Variables were recorded before and after a mean period of 213 days (range 89-297 days) after the change in the route of administration.. The mean epoetin-alpha do had to be increased from 159+/-104 to 185+/-122 U/kg/week (p<0.0001) to maintain a constant Hb level (121+/-12 vs 120+/-11 g/l). Plasma ferritin, albumin, C-reactive protein, iron, iron transferrin saturation and body mass index remained constant. The relative increase in epoetin-alpha dose was negatively correlated with the s.c. dose prior to the switch (R=-0.3; p<0.0001), with the most pronounced dose increases occurring in patients who received a low s.c. dose.. A switch from s.c. to i.v. administration of epoetin-alpha in haemodialysis patients was accompanied by an increase in the mean dose requirement of 15%. This increase may be less pronounced in patients receiving high s.c. doses prior to the switch.

Topics: Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Treatment Outcome

It is unknown to what degree physicians adjust erythropoietin doses to achieve hemoglobin levels (11.0 to 12.0 g/dL [110 to 120 g/L]) recommended by the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) for patients with end-stage renal disease receiving hemodialysis. Our objective is to examine epoetin alfa prescribing patterns for achieving the target hemoglobin level range in this population.. Monthly hemoglobin levels and epoetin alfa doses from 2 large databases were retrospectively analyzed. One data set comprised 31,267 patients from the Fresenius Medical Care-North America (FMC-NA) database, and the other comprised 128,761 patients based on claims for Medicare services.. Longitudinal evaluation of the FMC-NA data set showed that hemoglobin levels in patients administered epoetin alfa cycled in and out of the NKF-K/DOQI hemoglobin target range, and doses were decreased in 98.8% of patients with persistent hemoglobin levels greater than 12.0 g/dL (> 120 g/L). Hemoglobin levels in patients from the Medicare data set that initially were outside the target range migrated into the range with epoetin alfa dose titration. FMC-NA patients with a 3-month average hemoglobin level less than 11.0 g/dL (< 110 g/L) were administered significantly greater epoetin alfa doses than those with average hemoglobin levels greater than 12.0 g/dL (> 120 g/L; 21,838 versus 13,503 U/wk; P < 0.0001). Less than 0.4% of patients administered epoetin alfa were persistently anemic (hemoglobin < 11.0 g/dL [< 110 g/L]) and were administered persistently high doses (> 30,000 U/wk), but failed to respond with a 0.5-g/dL or greater (> or = 5-g/L) increase in hemoglobin levels.. In these analyses, few hemodialysis patients experienced persistent anemia while being administered high epoetin alfa doses. Physicians appeared to appropriately adjust doses to achieve hemoglobin levels recommended by the NKF-K/DOQI guidelines.

Topics: Anemia; Cross-Sectional Studies; Databases, Factual; Dose-Response Relationship, Drug; Drug Prescriptions; Drug Utilization; Epoetin Alfa; Erythropoietin; Guideline Adherence; Hemoglobins; Humans; Kidney Failure, Chronic; Practice Guidelines as Topic; Practice Patterns, Physicians'; Recombinant Proteins; Retrospective Studies; Treatment Outcome; United States

This retrospective observational survey assessed, in a routine clinical practice setting, the modalities of treatment with recombinant erythropoietic agents: alpha erythropoietic agents [epoetin alpha (Eprex) and darbepoetin alpha (Aranesp)] and epoetin beta (NeoRecormon). Evolution of haematological response parameters such as haemoglobin (Hb) during treatment of anaemic patients with cancer were contrasted for the different agents. Records of 125 consecutive adult cancer patients (42 epoetin alpha, 40 epoetin beta, 43 darbepoetin alpha) receiving chemotherapy and erythropoietic treatment for anaemia, and treated between September 2003 and February 2004, were analysed. Mean periods of observation of treatment were 103 days (epoetin alpha), 114 days (epoetin beta) and 95 days (darbepoetin alpha). The mean changes in maximum Hb level during treatment were 2.8 g/dl (epoetin alpha), 3.3 g/dl (epoetin beta) and 2.1 g/dl (darbepoetin alpha) (P=0.02, epoetin beta versus darbepoetin alpha). The proportions of patients achieving > or =1 g/ dl Hb increases were 85.7% (epoetin alpha), 87.5% (epoetin beta) and 79.1% (darbepoetin alpha). The mean cumulative doses administered to achieve these increases were 284, 722 IU; 201, 428 IU; and 208, 823 IU [dose calculated (based on equivalent peptide mass) using 1 microg darbepoetin alpha is equivalent to 200 IU epoetin], respectively. The proportions of patients achieving > or =2 g/dl Hb increases were 66.7% (epoetin alpha), 77.5% (epoetin beta) and 58.1% (darbepoetin alpha). This survey suggests that in real-life clinical conditions the available erythropoietic agents increase Hb effectively in anaemic patients with cancer, and that epoetin beta therapy may have therapeutic advantages over the other agents assessed.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies; Time Factors; Treatment Outcome

Erythropoiesis-stimulating proteins, such as erythropoietin alfa and darbepoetin alfa, have positively impacted anemia management. These medications improve patient outcomes and quality of life. Their costs, however, remain a major barrier for health systems.. To evaluate the development, implementation, and cost-effectiveness of an inpatient therapeutic interchange protocol for erythropoiesis-stimulating proteins at a large, tertiary care, university-affiliated health system.. Virginia Commonwealth University Health System (VCUHS) developed and implemented a therapeutic interchange program to convert therapy for all inpatients undergoing dialysis from erythropoietin alfa to darbepoetin alfa for treatment of chronic kidney disease-related anemia. An evaluation of the economic impact of this program on drug expenditures over a fiscal quarter (2003) was conducted using historical comparator data (2002).. Preliminary evaluation of the program demonstrated cost-savings and reduced drug utilization of erythropoiesis-stimulating proteins in hospitalized dialysis patients. For the first quarter of 2003 compared with the first quarter of 2002, VCUHS realized a cost-savings of nearly 10,000 US dollars, which was related to the program's aggressive screening procedure. When these data were normalized for equal numbers of patients in each group receiving one of the drugs, the actual cost-savings was over 2000 US dollars. These cost-savings are largely due to reduced utilization of these expensive biotechnology products with implementation of a dosing protocol.. VCUHS has successfully developed and implemented a darbepoetin alfa therapeutic interchange protocol for hospitalized dialysis patients. This has translated into reduced use of erythropoiesis-stimulating proteins, resulting in cost-savings for the health system.

Topics: Anemia; Chronic Disease; Clinical Protocols; Costs and Cost Analysis; Darbepoetin alfa; Drug Administration Schedule; Drug Utilization Review; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Hospitals, University; Humans; Injections, Intravenous; Kidney Diseases; Length of Stay; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Therapeutic Equivalency; Virginia

In 1997, the Health Care Financing Administration Hematocrit Measurement Audit (HMA) program initiated use of a 3-month rolling average hematocrit (Hct) level for reimbursement of epoetin claims in hemodialysis patients, with denial of payment when this value exceeded 36.5%. This study evaluated the impact of the HMA program on anemia-related outcomes in hemodialysis patients. An observational, retrospective study of 987 hemodialysis patients from 11 dialysis centers in the United States was performed, collecting data between October 1996 and December 1997. Centers were selected from a pool of nearly all facilities in the United States, which during May 1997 satisfied one of two criteria: greater than 75% of patients at the facility had mean Hct level of > or =33% (Group A) or fewer than 50% of patients at the facility had mean Hct level of > or =33% (Group B). Each facility maintained its own anemia management practices without specific anemia management interventions as part of this study. Hct level, hemoglobin (Hb) level, and epoetin dose were analyzed to compare the pre-HMA period (October 1996 to May 1997) to the HMA period (June to December 1997) and/or for each of the five quarters of the study period. The primary study endpoint was the percentage of patients with Hct levels of > or =33% during each study quarter. The mean Hct level at baseline was 34% in Group A and 33.4% in Group B (p = 0.01). Hct levels, which were increasing before implementation of the HMA program, decreased during the HMA period (p < 0.001 and p = 0.013 in Groups A and B, respectively). The percentage of patients in Groups A and B with mean quarterly Hct levels of > or =33% decreased during the last quarter of the HMA implementation period compared to the quarter immediately preceding the start of the HMA program (p < 0.001 for both comparisons). Changes in Hb levels were similar to those seen in Hct levels. The mean epoetin dose administered decreased from 13,090 U/week at the start of the study to 11,884 U/week immediately before the HMA program took effect (p < 0.05). The HMA program adversely affected anemia treatment outcomes, regardless of whether dialysis units before HMA implementation had <50% of patients with a Hct level of > or =33% or had >75% of patients with a Hct level of > or =33%. The decline in mean weekly dose of epoetin was likely a result of withholding doses out of concern among providers about risk of reimbursement denial.

Topics: Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Health Policy; Hematocrit; Humans; Insurance, Health, Reimbursement; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Epoetin alfa (EPO) and darbepoetin alfa (DARB) are approved for the treatment of chemotherapy-related anemia (CRA) in patients with nonmyeloid malignancies. This study examined dosing and hematologic outcomes with these agents in community oncology clinics.. Medical charts were abstracted retrospectively for 1005 patients (527 EPO, 478 DARB) with CRA (hemoglobin [Hb] < or = 11 g/dL) who received EPO or DARB at 10 U.S. oncology clinics between January 2002 and March 2003.. Outcome measures included dose and frequency of erythropoietic therapy, change in Hb at 4, 8, and 12 weeks after initiation of therapy, and transfusion of packed red blood cells.. Baseline characteristics were generally similar between groups. Most EPO-treated patients received EPO once weekly, but 25% received EPO every 2-3 weeks, with 40,000 U the predominant dose. DARB was usually given every 1-2 weeks in doses ranging from 200-400 mcg/injection. Mean treatment duration was relatively short (< 8 weeks) in both groups, with a similar number of Hb determinations and similar incidence of red blood transfusion between groups. Hb increased from baseline in the EPO and DARB groups at 4 weeks (0.99 vs. 0.69 g/dL, p = 0.003), 8 weeks (1.39 vs. 1.06 g/dL, p = 0.011), and 12 weeks (1.43 vs. 1.11 g/dL, p = 0.055). Early Hb response (> or = 1 g/dL increase by 4 weeks) was more common with EPO than DARB (48% vs. 38%, p = 0.008).. EPO was superior to DARB for early hematologic outcomes in patients with CRA in community oncology clinics. Retrospective data collection and relative inexperience with DARB at the time of the study may limit the generalization of these results. Randomized, controlled trials comparing EPO and DARB are warranted.

Topics: Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Recombinant Proteins; Retrospective Studies

To compare the cost-effectiveness of epoetin alfa (EPO) and darbepoetin alfa (DARB) for the treatment of chemotherapy-induced anemia (CIA), using dosing regimens approved by the FDA (EPO 40,000 U once weekly and DARB 2.25 U once weekly and DARB 2.25 mcg/kg once weekly).. The study compared published results of two double-blind, randomized, phase III trials one utilizing EPO (N = 166) and the other, DARB (N = 367). Patients in both trials similar baseline characteristics. Effectiveness was measured as the proportion of EPO or DARB patients who were successfully treated (i.e., did not require blood transfusion) during weeks 0-16 and 5-16, respectively. Estimated drug costs were presented in 2005 USD based on wholesale acquisition cost (WAC) and average drug utilization over 16 weeks. Cost-effectiveness was calculated as the estimated drug costs divided by transfusion effectiveness. Threshold analysis was used to determine the break-even point at which EPO and DARB had the same drug costs.. Estimated drug costs over 16 weeks were $9,039 for EPO and $13,555 for DARB. During weeks 5-16, 85% of EPO patients and 73% of DARB patients were successfully treated, resulting in average cost-effectiveness ratios of $106 for EPO and $186 for DARB per one per cent of successfully treated patients. A 33% reduction in DARB WAC was required to achieve the same drug costs as for EPO.. Utilizing FDA-approved doses, EPO was found to result in lower drug costs and better treatment success when compared to DARB. Hence, EPO is a dominant alternative compared to DARB for the treatment of CIA. The analyses presented here are not without limitations. Specifically, although the studies were comparable, patients were ultimately drawn from different populations.

Topics: Anemia; Antineoplastic Agents; Clinical Trials, Phase III as Topic; Darbepoetin alfa; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Patient Selection; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Anemia; Bias; Biomarkers; Chronic Disease; Epoetin Alfa; Erythropoietin; Goals; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Randomized Controlled Trials as Topic; Recombinant Proteins; Reference Values; Research Design; Treatment Outcome

Topics: Anemia; Cost Savings; Cost-Benefit Analysis; Darbepoetin alfa; Delivery of Health Care; Drug Utilization; Epoetin Alfa; Erythropoietin; Humans; New Jersey; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins

(1) Current treatments for anaemia in patients receiving cancer chemotherapy include blood transfusion and epoetin alfa and beta. These epoetins correct anaemia in 40% to 65% of patients and reduce the number of patients who require transfusions during the second and third months of treatment by 12-35% in absolute terms. (2) Darbepoetin alfa is slightly more glycosylated than epoetin alfa and beta. It is no more effective than these two drugs in chronic renal failure. Darbepoetin alfa is now approved for the treatment of anaemia in patients who are receiving chemotherapy for non myeloid malignancies. (3) Two placebo-controlled dose-finding studies and two placebo-controlled trials involving nearly 1000 patients in total have shown that darbepoetin alfa decreases the number of transfused patients by 17-25% in absolute terms, and that it probably reduces fatigue. However, one-quarter of patients receiving darbepoetin were nonetheless transfused. (4) In the absence of reliable comparisons, there is no firm evidence that darbepoetin alfa is more effective than other epoetins. (5) According to relatively imprecise company reports, darbepoetin alfa increased the risk of thromboembolic events during clinical trials (6% versus 3%), including pulmonary embolism (1.3% versus 0%); the company also states that darbepoetin alfa does not increase the risk of arterial hypertension, a classical effect of epoetin that is mentioned in the summary of product characteristics (SPC). Placebo-controlled trials and dose-finding studies show no impact on the outcome of cancer, but follow-up is limited and a negative effect cannot be ruled out. The company states that no cases of erythroblastopenia have occurred among more than 70 000 treated patients. (6) According to the SPC, darbepoetin alfa can be given once a week. However, the optimal epoetin dosing schedule is unknown. Epoetin therapy takes several weeks to correct anaemia, whereas transfusion is immediately effective. (7) In practice, darbepoetin alfa seems a little easier to administer than epoetin alfa or beta, but the advantages and disadvantages of these drugs as compared with blood transfusion are not entirely clear.

Topics: Anemia; Blood Transfusion; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Humans; Recombinant Proteins; Treatment Outcome

Although previous studies have recognized that timely correction of anemia is desirable, no published research quantifies the association between the timeliness of the hemoglobin rise and patients' outcomes. This study evaluates whether anemic patients with cancer who are receiving chemotherapy and who experienced an early response to epoetin alfa (> or = 1 g/dL hemoglobin increase at the end of 4 weeks of treatment) experienced better clinical and drug utilization outcomes compared with patients who did not experience an early response. Three large, open-label, community studies of epoetin alfa for the treatment of chemotherapy-related anemia were retrospectively analyzed to assess the association of early hemoglobin response to subsequent transfusion requirements, subsequent hemoglobin response, quality of life, and epoetin alfa dosage administered over the study. Two epoetin alfa dosing regimens were evaluated: 10,000 units 3 times weekly with potential escalation to 20,000 units, and 40,000 units once weekly with potential escalation to 60,000 units. In all studies, patients who experienced an early hemoglobin response had statistically lower subsequent transfusion requirements, higher rates of subsequent hemoglobin response, shorter time to hemoglobin response, better improvements in quality of life scores, and lower average weekly epoetin alfa dose than patients who did not experience an early hemoglobin response. Similar proportions of patients experienced early response in the 3-times weekly and once-weekly epoetin alfa regimens. This ad hoc analysis found that early hemoglobin response to epoetin alfa therapy was associated with improved clinical benefits and drug utilization. Early hemoglobin response may therefore be considered as a desired goal of epoetin alfa therapies.

Topics: Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Quality of Life; Recombinant Proteins; Retrospective Studies; Time Factors; Treatment Outcome

The cost of darbepoetin alfa versus that of epoetin alfa in a hospital setting was studied.. The study was an observational, retrospective review of the hospitalwide use of darbepoetin and epoetin during hospital admissions beginning in the period from January 2003 through April 2003. After the identification from daily charge reports of patients who used at least one of the study drugs during an admission, charts were requested for review. Drug product costs were determined from hospital purchasing information. Material and labor costs were combined to estimate drug administration costs. Total costs were calculated as the sum of drug product costs and administration costs.. A total of 429 epoetin records and 80 darbepoetin records were included. The two cohorts were similar with respect to demographic characteristics. With respect to costs, the only significant difference between cohorts was in daily administration costs, which were lower for patients receiving darbepoetin. Sensitivity analysis found lower costs for darbepoetin only after the dose-conversion ratio (DCR) was increased to above 256.74 units:1 microg. The overall DCR based on the median daily dose of each drug was 244.90 units:1 microg.. A cost-minimization study in a hospital showed no cost difference between treatment with epoetin and darbepoetin.

Topics: Anemia; Darbepoetin alfa; Drug Costs; Epoetin Alfa; Erythropoietin; Hemoglobins; Hospital Costs; Hospitals; Humans; Kidney Diseases; Length of Stay; Neoplasms; Recombinant Proteins

Topics: Anemia; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cyclophosphamide; Doxorubicin; Epoetin Alfa; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Neutropenia; Polyethylene Glycols; Positron-Emission Tomography; Prednisone; Recombinant Proteins; Rituximab; Stomach Neoplasms; Vincristine

Oxidative stress often occurs in chronic hemodialysis (HD) patients. The objective of our study was to investigate the interrelationship between oxidative stress and the degree of renal anemia.. In 107 consecutive HD patients, serum concentrations of two major aldehydic lipid peroxidation (LPO) products, 4-hydroxynonenal (HNE) and malondialdehyde (MDA), and of protein carbonyls were analyzed as parameters of oxidative stress and related to the degree of renal anemia. Additionally, in 76 patients treated with epoetin long-term changes in the serum levels of aldehydic LPO products were observed.. In HD patients, serum levels of HNE, MDA, and protein carbonyls are increased in comparison to controls. The lower the hemoglobin, i.e. the stronger the degree of renal anemia, the higher the serum concentrations of HNE, MDA, and protein carbonyls. The HNE and MDA levels decreased during HD. Long-term studies on the correction of renal anemia by epoetin demonstrated a mitigation of oxidative stress during this therapy. During periods of 1 and 2 years, it was observed that the serum levels of HNE and MDA could be reduced.. Chronic renal failure is connected with oxidative stress which correlates with the degree of renal anemia, and the serum levels of aldehydic LPO products could be reduced during correction of renal anemia by epoetin.

Topics: Aged; Aldehydes; Anemia; Blood Proteins; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins

Epoetin alfa administered s.c. three times weekly or once weekly increases hemoglobin (Hb) levels, decreases transfusion requirements, and improves quality of life in anemic cancer patients receiving chemotherapy. This study assessed the feasibility of using higher initial doses of once-weekly epoetin alfa followed by less frequent maintenance doses to increase and then maintain adequate Hb levels in this population.. In this open-label, nonrandomized, pilot study, anemic (baseline Hb < or = 11 g/dl) cancer patients undergoing chemotherapy received initial doses of epoetin alfa of 60,000 U s.c. once weekly to increase Hb levels by at least 2 g/dl, followed by 120,000 U s.c. every 3 weeks to maintain Hb levels. The maximum treatment duration was 24 weeks.. The mean baseline Hb level was 10.1 +/- 0.8 g/dl (n = 20). Once-weekly dosing resulted in mean Hb level increases of 1.0 +/- 1.1 g/dl by week 4 and 2.9 +/- 1.9 g/dl by week 8; 86% and 79% of patients evaluable at week 8 and week 12, respectively, demonstrated increases of at least 2 g/dl (target Hb level of > or = 12 g/dl). Thirteen patients (65%) received at least one maintenance dose; the mean Hb level increased from 12.8 +/- 1.1 g/dl before starting maintenance therapy to 13.3 +/- 1.4 g/dl at the last maintenance week. Both dosage regimens were well tolerated.. Once-weekly epoetin alfa at a dose of 60,000 U effectively increased Hb levels by week 8; 86% of patients achieved rises of at least 2 g/dl or Hb levels > or = 12 g/dl. Moreover, epoetin alfa at doses of 120,000 U every 3 weeks maintained or increased Hb levels. Results from this pilot study suggest that higher initial once-weekly dosing of epoetin alfa followed by less frequent maintenance dosing appears to be feasible for treating anemia in cancer patients undergoing chemotherapy. Further evaluation of these and other epoetin alfa dosage regimens is warranted.

Topics: Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Pilot Projects; Practice Guidelines as Topic; Recombinant Proteins

Topics: Anemia; Cell Hypoxia; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Disease Models, Animal; Dose Fractionation, Radiation; Epoetin Alfa; Erythropoietin; Female; Head and Neck Neoplasms; Hematinics; Hemoglobins; Humans; Male; Meta-Analysis as Topic; Neoplasm Recurrence, Local; Neoplasms; Pelvic Neoplasms; Placebos; Prognosis; Radiotherapy Dosage; Recombinant Proteins; Retrospective Studies; Risk; Risk Factors; Time Factors; Treatment Outcome; Uterine Cervical Neoplasms

To evaluate the efficacy of darbepoetin alfa 200 microg subcutaneously every 2 weeks after therapeutic substitution for epoetin alfa.. Retrospective multicenter chart review.. Three US Oncology-affiliated outpatient sites.. Three hundred thirty anemic patients with nonmyeloid malignancies, of whom 174 had been treated previously with epoetin alfa (switched group) and 156 had not been treated recently with epoetin alfa (naive group).. Therapeutic substitution with darbepoetin alfa was started according to the US Oncology Pharmacy and Therapeutics Committee's recommended dosing guidelines: anemic patients with cancer received a starting dosage of darbepoetin alfa 200 microg every 2 weeks regardless of whether or not they had previously received epoetin alfa. Hematologic and darbepoetin alfa usage data were abstracted from consecutive medical records dated from May 2002-March 2003.. Median exposure to darbepoetin alfa was 10 weeks (25th quartile 6 wks, 75th quartile 17 wks) and 10 weeks (25th quartile 5 wks, 75th quartile 18 wks) for the naive and switched groups, respectively. The week before the switch to darbepoetin alfa, the 174 patients receiving epoetin alfa were administered the following weekly doses: less than 40,000 U (9%), 40,000 U (50%), or 45,000-90,000 U (41%). Mean hemoglobin level increased from baseline (wk 0) in both the naive and switched groups. The proportion of patients receiving a red blood cell transfusion in the darbepoetin alfa treatment phase was low (15% in each group). No variation in transfusion rates was observed across weight categories in patients who received a fixed dosage of darbepoetin alfa. Darbepoetin alfa was well tolerated. A detailed usage algorithm was validated by these results and is being used in these three US Oncology-affiliated practices.. A darbepoetin alfa starting dosage of 200 microg subcutaneously every 2 weeks administered according to US Oncology-recommended dosing guidelines is effective in treating chemotherapy-induced anemia in both epoetin alfa-naive patients and those switched from epoetin alfa.

Topics: Aged; Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Injections, Subcutaneous; Male; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins; Retrospective Studies; Therapeutic Equivalency; Time Factors; Weight Gain

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Topics: Anemia; Disease Progression; Drug Industry; Epoetin Alfa; Erythropoietin; Health Policy; Hematinics; Humans; Marketing; Randomized Controlled Trials as Topic; Recombinant Proteins; Safety; Societies, Medical; Survival Analysis; Treatment Outcome

Current therapy for the treatment of hepatitis C virus (HCV) infection is standard interferon (IFN) or pegylated interferon (PEG-IFN) in combination with ribavirin (RBV). Hematologic side effects (neutropenia, thrombocytopenia, anemia) are a major reason for dose reduction of anti-HCV therapy. Because treatment adherence and maintenance of IFN or PEG-IFN and RBV doses have been shown to be important in achieving a sustained virologic response, appropriate management of hematologic side effects might play a substantial role in optimizing treatment outcomes. Neutropenia and thrombocytopenia are usually managed by IFN or PEG-IFN dose reduction; the role of hematopoietic growth factors to ameliorate these side effects needs further evaluation, but some studies suggest granulocyte colony-stimulating factor (G-CSF) may be useful in the management of IFN/PEG-IFN-associated neutropenia. Anemia is primarily due to RBV-induced hemolytic anemia, but IFN/PEG-IFN also suppresses bone marrow erythroid precursors. Treatment-induced anemia has usually been managed by RBV dose reduction or discontinuation. However, recent studies suggest that epoetin alfa can increase hemoglobin levels and facilitate maintenance of RBV dosage in patients with chronic hepatitis C who became anemic during standard combination therapy. Results of a randomized, randomized, double-blind, placebo-controlled trial suggest that epoetin alfa therapy can maintain RBV dosage, increase hemoglobin levels, and improve quality of life in this population. In patients who have chronic hepatitis C who experience hematologic toxicities during standard therapy, the use of hematopoietic growth factors such as epoetin alfa might have the potential to improve treatment adherence rates and allow optimal doses of IFN or PEG-IFN and RBV to be maintained, thereby leading to improved treatment outcomes.

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Hematinics; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Interferons; Neutropenia; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Thrombocytopenia

Topics: Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins

Anemia in human immunodeficiency virus (HIV)-infected patients can have serious implications, which vary from functional and quality-of-life decrements to an association with disease progression and decreased survival. In 2002, 16 members of the Anemia in HIV Working Group, an expert panel of physicians involved in the care of HIV-infected patients that met first in 1998, reconvened to assess new data and to translate these data into evidence-based treatment guidelines. The group reached consensus on the prevalence of anemia in the highly active antiretroviral therapy era; the risk factors that are independently associated with the development of anemia; the impact of anemia on quality of life, physical functioning, and survival; the impact of the treatment of hepatitis C virus coinfection on anemia in HIV-infected patients; evidence-based guidelines for treatment of anemia in HIV-infected patients, including the therapeutic role of epoetin alfa; and directions for future research.

Topics: Anemia; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antiviral Agents; Epoetin Alfa; Erythropoietin; Forecasting; Hepatitis C; HIV Infections; Humans; Quality of Life; Recombinant Proteins

Anemia is a common comorbidity with HIV. Before the highly active antiretroviral therapy (HAART) era, anemia was found to be associated with decreased survival. This study examined the prevalence of anemia since HAART's availability and the associations between anemia treatments and survival.. Anemia prevalence in a cohort of HIV-infected persons was described. In a smaller cohort of HIV-infected anemic patients, survival was modeled with a time-dependent proportional hazards regression model adjusting for CD4+ T-lymphocyte count, plasma HIV RNA concentration load, hemoglobin (Hb) level, and other factors.. Anemia (Hb level < 10.5 g/dL, or physician diagnosis) decreased from 13 to 5 percent (p < 0.05) in 1996 through 2001. Anemia prevalence was highest (24-35%) and did not decrease among patients with CD4 count less than 100 cells per mL. In total, 216 severely anemic HIV-infected individuals (mean Hb level, 8.1 g/dL) followed for a median of 13 months had a 37-percent mortality rate. Of these, 22 percent were untreated (13% mortality rate), 42 percent received transfusion alone (52% mortality), 12 percent received epoetin alfa alone (19% mortality), and 24 percent received both (47% mortality). Transfusion was associated with a threefold excess mortality risk, but epoetin alfa prescription was not associated with mortality.. The prevalence of anemia decreased in the HAART era, and transfusion was positively associated with risk of death, suggesting limiting use of transfusions in nonemergency situations.

Topics: Adolescent; Adult; Anemia; Antiretroviral Therapy, Highly Active; Blood Transfusion; CD4 Lymphocyte Count; Cohort Studies; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; HIV Infections; Humans; Longitudinal Studies; Male; Middle Aged; Prevalence; Proportional Hazards Models; Recombinant Proteins; Survival Analysis; Treatment Outcome; Viral Load; Washington

Topics: Anemia; Blood Transfusion, Autologous; Drug Overdose; Epoetin Alfa; Erythropoietin; Ferritins; Humans; Iron Deficiencies; Orthopedic Procedures; Platelet Count; Preoperative Care; Recombinant Proteins; Research Design; Sample Size

Epoetin alfa (Eprex*; Johnson & Johnson, Manati, PR) has been used successfully to correct the anemia of chronic renal failure for more than 12 years. Anti-erythropoietin (anti-EPO) antibodies have been reported in a small number of patients, resulting in a blood disorder, pure red cell aplasia (PRCA). To evaluate the utility of a large-scale anti-EPO antibody screening program in patients with chronic kidney disease (CKD) administered epoetin alfa, a study involving 5 large renal centers in southern Ontario, Canada, was conducted.. More than 1,500 hemodialysis, peritoneal dialysis, and predialysis patients were screened for the prevalence of anti-EPO antibodies by means of a radioimmunoprecipitation (RIP) assay. Serum samples were drawn and shipped to PPD Development (Richmond, VA) for the immunoprecipitation assay. Serum EPO levels also were measured. All samples that tested positive or borderline for antibodies were sent to MDS Pharma Services (Montreal, Canada) for the neutralization assay.. Of 1,531 samples tested, 1 patient tested low-positive and 3 borderline results were detected by means of RIP. PRCA previously was diagnosed in the patient with the low-positive antibody level; the patient was treated with cyclosporine and currently is being administered epoetin alfa with good response. The 3 patients with borderline antibody results manifested no clinical signs of PRCA. Neutralization assays performed on all 4 serum samples were negative for anti-EPO antibodies.. Results from this surveillance study show that the prevalence of antibody to EPO in patients with CKD administered epoetin alfa in 5 Canadian renal centers is low, and the value of a large-scale antibody screening program for PRCA cannot be justified.

Topics: Aged; Aged, 80 and over; Anemia; Autoantibodies; Autoimmune Diseases; Cross-Sectional Studies; Cyclosporine; Epoetin Alfa; Erythropoietin; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Male; Mass Screening; Middle Aged; Ontario; Peritoneal Dialysis; Population Surveillance; Radioimmunoprecipitation Assay; Recombinant Proteins; Red-Cell Aplasia, Pure; Renal Dialysis

The objective of this retrospective observational cohort study was to compare the effectiveness of darbepoetin alfa with that of epoetin alfa in patients with chemotherapy-induced anemia using data from noncontemporaneous chart audits conducted at a community-based oncology practice.. For the first chart audit, data were collected from consecutive patients with nonmyeloid malignancies with diagnoses of chemotherapy-induced anemia and hemoglobin levels < or = 10.5 g/dl who were receiving concurrent chemotherapy and had at least 5 weeks of visits from July-September 2000. After therapeutic substitution of darbepoetin alfa for epoetin alfa for all patients with chemotherapy-induced anemia, data were collected from consecutive darbepoetin alfa-treated patients with diagnoses of chemotherapy-induced anemia and at least 8 weeks of visits from June-October 2002 (darbepoetin alfa was approved in July 2002).. Most (86%) of the 212 epoetin alfa-treated patients had received an initial dose of 40,000 U once weekly, and most (85%) of the 196 darbepoetin alfa-treated patients had received a fixed dose of either 100 microg once weekly (49%) or 200 microg every 2 weeks (36%). At 8 weeks, the mean change in hemoglobin level was 1.1 g/dl for the darbepoetin alfa patient group and 1.0 g/dl for the epoetin alfa patient group.. Utilization, dose escalation rates, and clinical outcomes were considered comparable for the darbepoetin alfa and epoetin alfa patient groups.. Darbepoetin alfa, 100 microg once weekly or 200 microg every 2 weeks, appears to be as effective as epoetin alfa, 40,000 U once weekly, for the treatment of chemotherapy-induced anemia in the clinical practice setting.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies; Treatment Outcome

Recombinant Human Erythropoietin (EPO) is extensively used for anemia in renal failure patients. It is normally safe and effective, improving symptoms of anemia. We report here a case of renal anemia in a patient undergoing peritoneal dialysis (PD) for end stage renal failure from renovascular disease. He initially responded well to Epoetin alpha (Eprex) but subsequently developed EPO antibodies and pure red cell aplasia (PRCA), becoming blood transfusion dependent. Subsequently, he responded to Darbepoetin alpha (Aranesp), without any complications in the presence of persisting EPO antibodies. This positive response, which restored hemoglobin values to normal, occurred despite general belief that any form of EPO will cross-react to EPO antibodies. This is the first case report where PRCA with EPO antibodies responded well to another EPO preparation without intervention from immunosuppression therapy.

Topics: Aged; Aged, 80 and over; Anemia; Antibodies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Male; Peritoneal Dialysis; Recombinant Proteins; Red-Cell Aplasia, Pure

The recommended conversion dose for changing from epoetin alfa to darbepoetin alfa is 200 units to 1 microg. However, this may result in the over treatment of uraemic anaemia.. All in-centre haemodialysis patients (n = 60) were converted from an existing subcutaneous epoetin alfa regimen to weekly intravenous darbepoetin alfa. The protocol for anaemia management included a target haemoglobin (Hb) concentration of 120-130 g/L and a ferritin of 300-600 microg/L. Patient treatments were converted from subcutaneous epoetin alfa to weekly, intravenous darbepoetin alfa at month 0, at a conversion dose of 200 units epoetin alfa to 1 microg darbepoetin.. Both Hb and ferritin concentrations remained within the target range, but darbepoetin dosages fell from 50.8 to 42.3 microg/week by month 3 (P = 0.02). The initial conversion factor of 210 units/microg rose to 275 units/microg (P = 0.01) at month 4. No difference in conversion dosage could be determined between patients who were epoetin sensitive (<200 units/kg per week) or resistant (>200 units/kg per week, P = NS). Patients were then switched to fortnightly darbepoetin alfa dosing treatments; the existing weekly dose being doubled and Hb levels fell from 125 to 110 g/L (P < 0.0001), despite an increase in the mean dose from 44.9 to 47.5 microg/week (P = 0.02).. The original dosage reduction after the switch from epoetin alfa to weekly intravenous darbepoetin alfa may offset the increased relative cost of the latter. When administered weekly and intravenously, darbepoetin alfa maintains Hb at a more favourable conversion rate than is currently recommended.

Topics: Anemia; Darbepoetin alfa; Drug Administration Schedule; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Uremia

Topics: Anemia; Cost-Benefit Analysis; Darbepoetin alfa; Drug Costs; Epoetin Alfa; Erythropoietin; Humans; Recombinant Proteins

The sudden interruption of recombinant human erythropoietin (rHuEPO) in end-stage renal disease (ESRD) patients leads to rapid anemization. The mechanisms of this phenomenon are, however, insufficiently understood. The present study examined the response to immediate rHuEPO withdrawal in dialysis patients.. 10 chronic hemodialysis (HD) patients regularly receiving rHuEPO were studied. rHuEPO was stopped and reinitiated after 7 days. Reticulocyte profile, haemoglobin and haematocrit were measured at 0, 7 and 15 days. As a complementary study, and with the purpose of analyzying whether uremia was a relevant factor, 10 non-uremic male Wistar rats were treated with rHuEPO. After two weeks, rHuEPO was withdrawn in 5 animals, and continued for 7 additional days in the remainder. The same variables than in the human study were determined.. Changes in reticulocyte subtypes from baseline to day 7 were: total 18.2 +/- 0.9 vs 14.3 +/- 1.8% (p < 0.06); high-fluorescence (HFR): 2.6 +/- 0.4 vs 0.75 +/- 0.2 (p < 0.001); medium-fluorescence (MFR): 13.0 +/- 1.1 vs 6.6 +/- 0.9% (p < 0.02); and low-fluorescence (LFR): 84.2 +/- 1.4 vs 92.7 +/- 1% (p NS). The baseline pattern was recovered upon 7 days of rHuEPO reinitiation (p NS). Mean hemoglobin and hematocrit decreased by day 14 (p < 0.02) in spite of rHuEPO reinitiation at day 7. In non-uremic rats, changes were similar to that in the ESRD patients.. rHuEPO induces changes in the reticulocyte pattern, consisting in a reduction of immature reticulocytes. These changes appear to be independent of the presence of uremia. Accordingly, complete rHuEPO withdrawal in HD patients will cause a rapidly-developing anaemia due to an alteration in the reticulocyte maturation series; therefore, sudden rHuEPO interruption should be avoided whenever is possible. As a collateral application, the specific changes described herein have potential use for detecting illegal administration of rHuEPO.

Topics: Aged; Anemia; Animals; Doping in Sports; Drug Administration Schedule; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Male; Middle Aged; Rats; Rats, Wistar; Recombinant Proteins; Recurrence; Renal Dialysis; Reticulocyte Count; Uremia

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Meta-Analysis as Topic; Recombinant Proteins

Lung cancer is associated with the one of the highest rates of anaemia of all solid tumours. Anaemia has a negative impact on treatment outcome and overall survival of patients with cancer and also affects their quality of life. Recombinant human erythropoietin (epoetin) provides an effective and safe treatment of cancer-related anaemia without the risks associated with red blood cell transfusion. Epoetin therapy increases haemoglobin levels, reduces the need for blood transfusions and improves the quality of life of patients with anaemia and lung cancer. Epoetin beta is also effective for preventing the development of anaemia and decreasing transfusion requirements when administered with concomitant platinum-based chemotherapy. In addition, preliminary evidence suggests that treatment with erythropoietic agents may improve survival of lung cancer patients, although this needs to be verified in prospective clinical trials specifically designed to evaluate survival. Therefore, early initiation of epoetin beta to prevent chemotherapy-associated anaemia may represent the best strategy for patients with lung cancer being treated with chemotherapy.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Lung Neoplasms; Quality of Life; Recombinant Proteins; Survival

Topics: Anemia; Cost-Benefit Analysis; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Humans; Recombinant Proteins

Anemia is a frequent complication of end-stage renal disease. Poor responsiveness to epoetin therapy hampers the management of anemia. Escalating epoetin doses often are used to overcome epoetin resistance. The objective of this study is to examine the relationship between epoetin dose requirements and mortality.. Using United States Renal Data System administrative claims data, we conducted a retrospective cohort study of 94,569 prevalent hemodialysis patients in 2000 and 2001. A Cox proportional hazard regression analysis, adjusted for baseline variables, and a 5-knot cubic regression spline were used to model the dose-response relationship between epoetin and all-cause mortality.. Significant interpatient variation exists in epoetin dose requirements to attain defined hematocrit levels. For every hematocrit cohort studied, patients administered higher doses of epoetin had significantly lower hematocrit values and greater mortality rates. Using the cubic spline function, a significant nonlinear relationship between increased epoetin dose and mortality was found regardless of hematocrit (P < 0.0001), with the steepest increase in relative risk for death found after the 72.5th dose percentile.. Epoetin dose requirement is an independent predictor of total mortality in hemodialysis patients after adjustment for hematocrit. Poor responders who continue to have low hematocrit values despite the administration of high epoetin doses may not necessarily benefit from more epoetin, but perhaps should be considered for other adjunctive therapies. In contrast to conventional wisdom, this study suggests that epoetin dosing requirements could provide important prognostic information beyond that predicted by hematocrit alone.

Topics: Aged; Anemia; Black People; Cohort Studies; Dose-Response Relationship, Drug; Drug Resistance; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Humans; Incidental Findings; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Sensitivity and Specificity; United States; White People

To investigate effects of early correction of anemia on the rate of cardiovascular complications and survival on regular hemodialysis (RHD).. Eighty patients with chronic renal failure (CRF) on regular hemodialysis entered two groups: group 1 with hemoglobin (Hb) < 80 g/l (n = 36) and group 2 with Hb > 100 g/l (n = 44). 90% patients of group 2 were treated for renal anemia for 6-8 months of predialysis CRF. When placed on RHD, group 1 started therapy with epoetin, 39 patients of group 2 continued epoetin treatment.. Patients of group 2 had a higher rate of eccentric left ventricular hypertrophy (LVH) with reduced ejection fraction and development of congestive cardiac failure and coronary heart disease. Eccentric LVH in group 1 patients regressed only in 80% when the patients were on hemodialysis and received epoetin for correction of anemia. Overall cardiac death in group 1 was twice that of group 2 patients.. Early correction of anemia led to a 50% increase in 5-year survival. This fact can be explained with inhibited progression of eccentric LVH.

Topics: Adult; Anemia; Cardiotonic Agents; Case-Control Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Ventricular Function, Left

Topics: Anemia; Animals; Cell Hypoxia; Clinical Trials as Topic; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Insurance, Health, Reimbursement; Kidney Failure, Chronic; Male; Medicare; Middle Aged; Quality of Life; Recombinant Proteins; Renal Dialysis; Sickness Impact Profile; United States

Patients with end-stage renal disease requiring hemodialysis are frequently treated with epoetin alfa (recombinant human erythropoietin, rHuEPO) for anemia. The aim of this study was to determine whether successful management of anemia could be maintained by changing the dosing schedule of epoetin alfa from 2 or 3 times per week to once-weekly administration via not only the subcutaneous (s.c.) but also the intravenous (i.v.) route.. Patients included in the study had hemodialysis for > 12 months, treatment with epoetin for > or = 6 months and adequate iron stores. The study consisted of a pre-study period (12 weeks), Phase I (4 weeks, patients continued prestudy regimen), Phase II (12 weeks, once-weekly i.v. or s.c. regimen with dose adjustments permitted to maintain target hemoglobin (Hb) concentrations) and Phase III (4 weeks, once-weekly i.v. or s.c. regimen without dose adjustments).. The study was completed by 203 patients (per-protocol population: i.v. group, n = 115, s.c. group, n = 88). In the majority of patients (69.4% overall: i.v. group, 67.0%, s.c. group, 72.7%), the individual Phase I Hb concentrations were maintained within +/-1.0 g/dl (+/-10 g/l) during Phase III. In 79.3% of the patients (i.v. group, 75.7%, s.c. group, 84.1%), a stable Hb concentration (decrease of < or = 1 g/dl (< or = 10 g/l)) was maintained without statistically significant dose adjustments (82.4+/-33.8 - 86.8+/-42.1 IU/kg body weight/week). Hb concentrations decreased from 11.57+/-0.83 g/dl(115.7+/-8.3 g/l) in Phase I to 11.39+/-1.09 g/dl (113.9+/-10.9 g/l) in Phase III (p < 0.05) in the entire group. The weekly dose of epoetin alfa required to maintain the individual target Hb concentrations changed from 85.1+/-34.6 IU/kg in Phase I to 92.1+/-45.1 IU/kg in Phase III in the entire population (p <0.05).. With once-weekly administration of epoetin alfa, Hb concentrations can be maintained in the majority of stable hemodialysis patients, and only minimal dose adjustments are required.

Topics: Anemia; Cross-Over Studies; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Safety

Topics: Aged; Anemia; Catheterization, Central Venous; Catheters, Indwelling; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematologic Tests; Humans; Male; Prospective Studies; Recombinant Proteins; Renal Dialysis; Risk Factors

Topics: Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Humans; Quality of Life; Recombinant Proteins

The PRE-dialysis survey on anaemia management (PRESAM) was designed to assess the care given to pre-dialysis patients in the 12 months before haemodialysis or peritoneal dialysis, with emphasis on anaemia management.. For this epidemiological study, a retrospective chart review was conducted for patients who started haemodialysis or peritoneal dialysis between 1 August, 1999 and 6 April, 2000. All adult patients who entered one of the 779 participating centres in 21 European countries, Israel or South Africa were included, except for patients who underwent dialysis only during an acute episode. In addition to demographic characteristics, the study examined the prevalence of anaemia, anaemia management including the use of iron supplementation and epoetin, source of referral to the dialysis centre, comorbidities and major clinical events.. A total of 4333 new dialysis patients were included in the survey. At the first visit to the dialysis centre, 68% of the patients had a haemoglobin (Hb) concentration < or = 11.0 g/dl; Hb concentration was positively correlated with creatinine clearance rate (r = 0.43, P < 0.01). Patients who received epoetin had a mean Hb concentration of 8.8 g/dl at the start of epoetin treatment, and 96% of these patients had an Hb concentration < or = 11.0 g/dl. Only 26.5% of the patients received epoetin before dialysis. The length of time under the care of a nephrologist was associated with meeting the European Best Practice Guidelines (EBPG) target Hb concentration, as well as receiving epoetin.. Few pre-dialysis patients met the EBPG target for Hb concentration, despite regular nephrology care.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Europe; Female; Health Surveys; Hemoglobins; Humans; Iron; Israel; Male; Practice Guidelines as Topic; Recombinant Proteins; Renal Dialysis; Retrospective Studies; South Africa; Time Factors

The Predialysis Survey on Anemia Management was designed to assess the care given to predialysis patients within 3 months of the start of hemodialysis or peritoneal dialysis (PD) therapy. In this presentation, we focus on demographic data and patient referral practices of patients who enter kidney centers.. We conducted a retrospective chart review of patients who had started hemodialysis or PD therapy between August 1999 and April 2000. All patients (age, 16 to 99 years) who entered 1 of the 779 centers in 21 European countries, Israel, or South Africa were included, except those for whom dialysis therapy was only started during an acute episode. Demographic characteristics, referral to kidney centers, comorbidities, drug treatments, major clinical events, and use of epoetin were documented.. Mean creatinine clearance rate at the first visit to the kidney center was 18.2 mL/min (0.303 mL/s). Of all patients, greater than 35% had a creatinine clearance less than 10.0 mL/min (<0.167 mL/s) at their first visit. Overall, 87% of patients were initiated on hemodialysis therapy, and 13% were started on PD therapy. PD was used more often the longer a patient was under the care of a nephrologist. Of 4,333 new dialysis patients, 68% had a hemoglobin concentration of 11.0 g/dL or less (< or =110 g/L) at the first visit.. The majority of patients in the survey had been under the care of a nephrologist for more than 12 months before the start of dialysis therapy. Nevertheless, most of these patients were anemic, and only a minority were on epoetin treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Chronic Disease; Epoetin Alfa; Erythropoietin; European Union; Female; Health Care Surveys; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Peritoneal Dialysis; Practice Guidelines as Topic; Recombinant Proteins; Referral and Consultation; Renal Dialysis; Retrospective Studies

Recombinant human erythropoietin (epoetin) is widely used for correction of anaemia in patients with chronic renal disease and its efficacy has been confirmed in numerous studies. Disturbances in carnitine metabolism may also contribute to the development of renal anaemia. Although increases in erythrocyte count (RBC) and changes in RBC metabolism during L-carnitine administration have been observed, supplementation with L-carnitine in anaemic hemodialysis patients is not routine. The aim of our study was to determine the influence of epoetin on hematological parameters and plasma carnitine profile in anaemic hemodialysis patients. 36 hemodialysis patients (22 men, 14 female, aged from 17 to 64 years, mean 43) and 30 healthy volunteers (12 men, 18 female, aged from 25 to 65 years, mean 40) were studied. Epoetin (Eprex, Janssen-Cilag) was administered subcutaneously for twelve months with the starting dose 2000 IU three times per week (range from 75 to 133, mean 102 +/- 21 IU/kg/week). The target hemoglobin (Hb) range at the time of the study was between 10-11 g/dL. Laboratory markers of hematological response, carnitine and iron status, were measured before epoetin administration and then controlled every three months. During epoetin treatment a significant increase in Hb concentration was observed (100% of patients responded to epoetin). In the third and six month of epoetin treatment, along with a significant increase in mean reticulocyte count and the highest increment of RBC count and Hb levels, probably due to increased erythropoiesis, a significant, transient decrease of mean total and free plasma carnitine levels was observed. This may suggest the utilisation of carnitine by a new RBC population. It also indicates that there is a need for L-carnitine in carnitine deficient maintenance hemodialysis patients particularily during erythropoiesis induced by epoetin treatment.

Topics: Adolescent; Adult; Aged; Anemia; Carnitine; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Reticulocyte Count

To determine the degree of anaemia corresponding to the decreasing levels of renal function in patients with chronic renal failure (CRF) and not yet on dialysis, and to assess the indications for treatment with recombinant erythropoeitin (epoetin).. We studied the relationship between haemoglobin (Hb) concentration and creatinine clearance (Ccr) in 403 consecutive patients with CRF regularly monitored in nephrology consultations between January 1 and June 30, 1999, and who received appropriate iron and vitamin supplementation. These patients were then followed-up until June 30, 2000 or until maintenance dialysis was initiated.. There was a significant and close correlation between the degree of anaemia and renal dysfunction. An Hb value<11 g/dl (corresponding to the present threshold for the indication of epoetin) was observed in 62% of patients with creatinine levels>400 micromol/l and in 58% when Ccr was<20 ml/mn/1.73 m2. Whatever the level of CRF, the degree of anaemia was higher in the women than in the men. Among the 123 patients who had to start maintenance dialysis during the observation period, 85 (69%) were treated with epoetin before dialysis was started.. In patients with CRF, clinically symptomatic anaemia is more frequent than imagined, and early treatment is required. Regular monitoring of Hb and iron levels is mandatory in order to allow patients to benefit from timely initiation of epoetin and thus prevent the development of disabling asthenia and other deleterious consequences of anaemia.

Topics: Adult; Age Factors; Aged; Analysis of Variance; Anemia; Creatinine; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Recombinant Proteins; Renal Dialysis; Sex Factors; Time Factors

Topics: Anemia; Bone Marrow; Epoetin Alfa; Erythropoietin; Humans; Injections, Intravenous; Injections, Subcutaneous; Iron; Iron Deficiencies; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma; Recombinant Proteins

Topics: Adult; Anemia; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Statistics, Nonparametric; Treatment Outcome

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase III as Topic; Darbepoetin alfa; Double-Blind Method; Drug Administration Schedule; Drug Costs; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Lung Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; United States

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Anemia; Contraindications; Epoetin Alfa; Erythroblasts; Erythropoietin; Humans; Recombinant Proteins; Renal Insufficiency

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hemoglobinometry; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Structure-Activity Relationship; Treatment Outcome

In 2000 and 2001, The Centers for Medicare & Medicaid Services (CMS) End-Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) project collected data on all in-center hemodialysis (HD) patients in the United States aged >or=12 and <18 years. There were 433 of 486 (89%) patients and 435 of 516 (84%) patients who had the minimum required data submitted and were included in the 2000 and 2001 study years, respectively. There were 188 patients (43%) who had data submitted in both study years, providing longitudinal data on this cohort. A comparison of clinical parameters on these 188 patients in the 2000 and 2001 study years reveals significant improvement in mean calculated spKt/V (1.50+/-0.36 vs. 1.58+/-0.30, P<0.01), mean hemoglobin (11.0+/-1.6 g/dl vs. 11.5+/-1.3 g/dl, P<0.001), mean ferritin (286+/-278 ng/ml vs. 460+/-353 ng/ml, P<0.001), mean transferrin saturation (27.8+/-15.1% vs. 31.3+/-15.0%, P<0.05), mean serum albumin as measured by the bromocresol green method (3.83+/-0.54 g/dl vs. 3.95+/-0.42 g/dl, P<0.01), and mean height standard deviation score (-1.814+/-1.756 vs. -1.699+/-1.657, P<0.05). In addition, 20 of 29 (69%) patients who had a spKt/V <1.2 in the 2000 study year had a spKt/V >1.2 in the 2001 study year. Of 68 (44%) patients who had a catheter as their HD access in the 2000 study year, 30 had an arteriovenous fistula or graft in the 2001 study year and 49 of 80 (61%) patients who had a mean hemoglobin <11 g/dl in the 2000 study year had a hemoglobin >11 g/dl in the 2001 study year. In summary, these longitudinal data demonstrate significant improvements in nearly all clinical parameters studied in these adolescent HD patients.

Topics: Adolescent; Adolescent Development; Anemia; Arteriovenous Shunt, Surgical; Body Height; Catheters, Indwelling; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Longitudinal Studies; Male; Recombinant Proteins; Renal Dialysis; Serum Albumin; Treatment Outcome

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins

We report the case of a patient with a severe chronic radiation enteropathy. She had been dependent on red cell transfusions for many years. On admission, she displayed anemia (8.6 g/dL) resulting from both inadequate EPO production and a functional iron deficiency. A 3-wk IV iron sucrose treatment (200 mg once weekly) resulted in an increased reticulocyte count, but did not raise the hemoglobin (Hb) level. The adjunction of epoetin alpha (10,000 IU three times a week) made it possible to reach the normal range (12.9 g/dL) after a 17-wk treatment. As the anti-anemic treatment discontinued, the Hb level decreased to 11.1 g/dL within 2 wk. Giving EPO again (10,000 IU twice a week) failed to maintain the Hb level, which dropped under basal values (7.8 g/dL). In contrast, a second combination EPO/iron sucrose did restore a normal Hb level and maintained it. This case report supports the combination of EPO and IV iron supplementation in patients with anemia of chronic disease and either an impaired iron absorption or intolerance to oral iron.

Topics: Anemia; Chronic Disease; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Middle Aged; Radiation Injuries; Recombinant Proteins; Reticulocyte Count

Data indicate that a wide range of factors can contribute to inter- and intrapatient variability in hemoglobin (Hb) levels in dialysis patients. Some of these factors are controllable and can be minimized by implementing nursing practices that encourage consistent and accurate Hb assessments and management. However, many of these factors are difficult or impossible to modify, and natural intrapatient variations are therefore expected and unavoidable. When natural variability leads to Hb levels that temporarily exceed 12 g/dL, appropriate protocol-guided nursing responses should include long-term, patient-specific laboratory trend analyses, data-driven adjustments in the anemia management prescription, and accurate nursing documentation of assessments, interventions, and outcomes.

Topics: Aged; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Anemia is a multifactorial problem in patients with human immunodeficiency virus (HIV) infection, cancer, and hepatitis C virus (HCV) infection. New insights regarding anemia symptoms and quality of life (QOL) have prompted reassessment of traditional triggers for anemia treatment to increase hemoglobin (Hb) and improve QOL. In HIV-positive patients, anemia is independently associated with disease progression and survival. Many HIV-positive patients receiving highly active antiretroviral therapy (HAART) still develop mild to moderate anemia and associated QOL impairment. Epoetin alfa effectively increases Hb and improves QOL in these patients. Many HIV-positive patients are coinfected with HCV. Standard HCV therapy (interferon alfa/ribavirin) can cause anemia that may result in treatment alterations and compromised virologic outcome. Epoetin alfa therapy in anemic HCV patients increases Hb levels and may provide other benefits. Neuroprotective effects of epoetin alfa in preclinical models of central nervous system disorders have recently been demonstrated, implying a new therapeutic role for this cytokine.

Topics: Anemia; Central Nervous System Diseases; Epoetin Alfa; Erythropoietin; Hepacivirus; Hepatitis C; HIV; HIV Infections; Humans; Neoplasms; Recombinant Proteins

Anemia commonly occurs in patients with cancer or human immunodeficiency virus (HIV) infection as a result of the disease, its treatment, or both. The negative impact of anemia on patient quality of life (QOL), functional status, and treatment outcomes underscores the need for its correction in these patients. In anemic patients with cancer or HIV infection, treatment with epoetin alfa increases hemoglobin (Hb) levels, decreases transfusion requirements, and improves QOL. In both settings, the gains in overall QOL have been significantly and directly related to increases in Hb, with maximum QOL gains in the range of Hb levels of 11-13 g/dL, supporting the need to achieve and maintain Hb levels > or =12 g/dL in an effort to preserve and maximize QOL benefits. A potential survival benefit has also been associated with correction of anemia in patients with HIV infection--and possibly in those with cancer as well.

Topics: Anemia; Clinical Trials as Topic; Disease Progression; Epoetin Alfa; Erythropoietin; HIV; HIV Infections; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Hepatitis C virus (HCV) infection is a significant worldwide health care problem. Nearly one-third of all patients infected with human immunodeficiency virus (HIV) are coinfected with HCV. Compared with HIV-monoinfected persons, coinfected individuals experience more rapid progression of fibrosis and higher incidence of cirrhosis and death as a result of liver disease. Treatment for HCV infection includes ribavirin (RBV) plus interferon alfa (IFN-alpha) or pegylated IFN, a combination treatment associated with anemia that may require RBV dose reduction or discontinuation. IFN-RBV-associated anemia is more profound among coinfected patients, who have a high prevalence of pretreatment anemia and may also be taking other medications causing anemia. Epoetin alfa administration to HCV-infected patients with IFN-RBV-related anemia can significantly increase hemoglobin levels and maintain significantly higher RBV doses compared with patients treated with RBV dose reduction alone. Higher RBV doses and adherence to HCV therapy have been associated with higher sustained virologic response (SVR) rates. Maintenance of RBV dose with epoetin alfa may improve adherence, thereby affecting SVR.

Topics: Anemia; Antiviral Agents; Epoetin Alfa; Erythropoietin; Hepacivirus; Hepatitis C, Chronic; HIV Infections; Humans; Interferon-alpha; Recombinant Proteins; Ribavirin

Recombinant human erythropoietin (r-HuEPO; epoetin alfa) is well established as safe and effective for the treatment of anemia. In addition to the erythropoietic effects of endogenous erythropoietin (EPO), recent evidence suggests that it may elicit a neuroprotective effect in the central nervous system (CNS). Preclinical studies have demonstrated the presence of EPO receptors in the brain that are up-regulated under hypoxic or ischemic conditions. Intracerebral and systemic administration of epoetin alfa have been demonstrated to elicit marked neuroprotective effects in multiple preclinical models of CNS disorders. Epoetin alfa has also been shown to prevent the loss of autoregulation of cerebral blood flow in a model of subarachnoid hemorrhage. The mechanisms of EPO-induced neuroprotection include prevention of glutamate-induced toxicity, inhibition of apoptosis, anti-inflammatory effects, antioxidant effects, and stimulation of angiogenesis. Collectively, these findings suggest that epoetin alfa may have potential therapeutic utility in patients with ischemic CNS injury.

Topics: Anemia; Central Nervous System; Central Nervous System Diseases; Clinical Trials as Topic; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Neuroprotective Agents; Recombinant Proteins

Data indicate that a significant percentage of dialysis patients do not achieve the hemoglobin (Hb) target range of 11 to 12 g/dL. Our dialysis facility undertook a quality improvement program to assess and modify the processes affecting anemia-related outcomes. A 30% reduction in the percentage of patients with Hb levels below 11 g/dL was achieved by: (a) empowering an anemia manager to coordinate the team quality improvement effort, (b) integrating the Epotein alfa and iron protocols, (c) implementing a dose titration model for patients with Hb levels in the upper end of the target range, and (d) devising a "rapid ramping" protocol to ensure timely achievement of target Hb levels in patients who were new to dialysis or returning to the facility after hospitalization.

Topics: Aged; Anemia; Clinical Protocols; Epoetin Alfa; Erythropoietin; Hemoglobins; Hospitalization; Humans; Iron; Male; Monitoring, Physiologic; Process Assessment, Health Care; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Neovascularization, Pathologic; Recombinant Proteins

Darbepoetin alfa is the second erythropoietic protein to be approved for the treatment of chemotherapy-induced anemia (CIA). In the clinical setting, darbepoetin alfa can be administered less frequently than epoetin alfa with similar efficacy. Practice patterns and outcomes associated with the use of darbepoetin alfa and epoetin alfa in the clinical setting have not been reported.. This study compared practice patterns and clinical outcomes of the use of darbepoetin alfa and epoetin alfa for CIA at oncology practices in the United States.. This was a multicenter retrospective cohort study. Data were abstracted from the medical charts of consecutive patients who began darbepoetin alfa treatment between August 1 and October 4, 2002, or epoetin alfa treatment between April 1 and July 31, 2002, and were receiving concurrent chemotherapy. These data were used to determine the initial dose and dosing schedule, dose changes, and changes in hemoglobin concentrations after 4, 8, and 12 weeks of treatment, adjusted for red blood cell (RBC) transfusions, and the incidence of RBC transfusions over time. To minimize potential bias, the study protocol defined specific end points and prespecified analytic techniques for assessing clinical outcomes with the 2 agents.. The records of 1391 patients from 16 community and hospital outpatient oncology clinics were abstracted. Of these, 1293 patients (93.0%) received only 1 erythropoietic agent (darbepoetin alfa, 735 [56.8%]; epoetin alfa, 558 [43.2%]); the remainder received both agents. In the patients who received darbepoetin alfa, most (553 [75.2%]) received an initial dosage of 200 microg q2wk. A similar proportion (414 [74.2%]) received epoetin alfa at an initial dosage of 40,000 U qwk. As these were the regimens for the majority of patients whose records were abstracted, the results reported here are for these patients. The dose was increased in 63 darbepoetin alfa recipients (11.4%) and 58 epoetin alfa recipients (14.0%) at a median of 7 weeks. After 12 weeks, the 2 groups had an identical mean imputed change from baseline in hemoglobin concentration (1.0 g/dL), and the incidence of RBC transfusions during treatment was also similar between groups (darbepoetin alfa, 44553 [8.0%]; epoetin alfa, 39414 [9.4%]).. Darbepoetin alfa 200 microg q2wk was used as a standard regimen for CIA at the 16 US oncology practices participating in this study. It appeared to be as effective as epoetin alfa 40,000 U qwk, with a reduced frequency of dosing.

Topics: Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Drug Utilization Review; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Practice Patterns, Physicians'; Recombinant Proteins; Retrospective Studies

Topics: Aged; Anemia; Autoantibodies; Diagnosis, Differential; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Recombinant Proteins; Red-Cell Aplasia, Pure

Topics: Anemia; Drug Costs; Drug Industry; Epoetin Alfa; Erythropoietin; Health Expenditures; Humans; Italy; Kidney Failure, Chronic; National Health Programs; Recombinant Proteins

Anemia management protocols provide a consistent, standardized, therapeutic approach that can help nurses and other members of the nephrology team achieve more stable Hb levels within the target range of 11 to 12 g/dL recommended by the NKF-K/DOQI. This article provides an overview of Winthrop University Hospital's anemia management protocol, with a focus on an Epoetin alfa algorithm that was developed to guide therapeutic interventions.

Topics: Algorithms; Anemia; Clinical Protocols; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Patient Care Planning; Recombinant Proteins; Renal Dialysis

Strategies for managing antineoplastic therapy-associated hematopoietic toxicity (thrombocytopenia, neutropenia, and anemia) are discussed. Hemorrhage secondary to decreases in platelets is the major risk posed by chemotherapy-induced thrombocytopenia. Patients with < 20,000 platelets per microliter are at increased risk of bleeding, particularly if they have a history of bleeding associated with this condition. The risks of infection and complications are related to both the severity and duration of neutropenia. The rate of febrile neutropenia with most antineoplastic regimens is < 40%, and routine use of cytokine therapy is probably not cost-effective. The frequency of cancer-related anemia is dependent on the type, stage, and duration of disease. Chemotherapy-induced anemia is affected by the types of agents used, the schedule of drug administration, and the intensity of the regimen. Fatigue is the most common symptom of anemia, being reported by 80-100% of patients undergoing chemotherapy. Although fatigue is a major factor in patients' quality of life, it has often not been treated systematically and aggressively. Anemia used to be treated with transfusions, but therapy with epoetin alfa is showing promise as an alternative. The introduction of epoetin alfa has led to more aggressive treatment. Chemotherapy-induced hematopoietic toxicity is a multifactorial challenge that affects the treatment of oncology patients.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Fatigue; Hematinics; Humans; Neutropenia; Practice Guidelines as Topic; Recombinant Proteins; Severity of Illness Index; Thrombocytopenia

Recent American and European guidelines recommend that epoetin therapy should be considered whenever the blood haemoglobin (Hb) level is <10-11 g/dl in dialysis patients and in pre-dialysis patients. Thus, data on the current prevalence of anaemia with respect to the degree of chronic renal insufficiency are needed in order to determine the potential indications of epoetin therapy in the pre-dialysis period.. We prospectively studied 403 consecutive ambulatory pre-dialysis patients whose serum creatinine (Scr) was 200 micro mol/l or more at their first passage at our out-patient clinic between January 1 and June 30, 1999. Hb and Scr values were determined at each visit until June 30, 2000, or until the start of maintenance dialysis. Patients had a clinical and laboratory evaluation every 2-3 months, and monthly when treated with epoetin.. The mean (+/-SD) age of patients was 60.9+/-17.2 years at presentation. The Hb level was <11 g/dl in 62% of patients with Scr > or =400 micro mol/l, and in 58% of patients with an estimated creatinine clearance (Ccr) <20 ml/min/1.73 m(2). The proportion of anaemic patients was higher for any given Ccr value in females than in males. A total of 136 patients were treated with epoetin during the observation period. At the start of epoetin, their mean Hb value was 9.5+/-0.6 g/dl and Ccr level 13.9+/-4.9 ml/min/1.73 m(2). Among the 123 patients who began maintenance dialysis therapy during the observation period, 85 (or 69%) received epoetin therapy before the start of dialysis. Their mean Hb value at the start of dialysis was 10.8+/-1 g/dl compared with 10.5+/-1.1 g/dl in the 41 dialysed patients who did not require epoetin therapy during the pre-dialysis period.. Based on the data gained in a large cohort of patients receiving regular pre-dialysis nephrological care, the proportion of subjects with a Hb level <11 g/dl may be estimated at approximately 60% when the Ccr is <20 ml/min/1.73 m(2). If the Hb level is to be maintained at no less than 11 g/dl, at least two-thirds of patients at this advanced stage of chronic renal failure should require pre-dialysis epoetin therapy.

Topics: Anemia; Creatinine; Cross-Sectional Studies; Epoetin Alfa; Erythropoietin; Female; France; Hemoglobins; Humans; Incidence; Kidney Diseases; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Regression Analysis; Renal Replacement Therapy; Sex Characteristics; Uremia; White People

Anemia occurs frequently in children with cancer, but there is little information quantifying the incidence of anemia or treatment. A survey was conducted in 1998 in Europe by The Research Partnership with the objective of determining the incidence of anemia, identifying the hemoglobin triggers that initiated anemia treatment, and the current anemia treatment options available to clinicians.. The survey was conducted in the 10 largest pediatric oncology centers each in France, Germany, Italy, Spain, and the UK, and in the 8 largest centers in both Belgium and The Netherlands. Telephone interviews with the most senior physician available in the institution were used to collect data, which included the numbers of patients treated or under follow-up, cancer types, and treatment practices for anemia.. Data were collected for 25,093 patients. Over 80% of patients were anemic (WHO: hemoglobin

Topics: Adolescent; Anemia; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Epoetin Alfa; Erythropoietin; Europe; Female; Health Surveys; Hematinics; Humans; Incidence; Infant; Infant, Newborn; Male; Neoplasms; Recombinant Proteins

Anemia resulting from cancer or its treatment is an important clinical problem increasingly treated with the recombinant hematopoietic growth factor erythropoietin. To address uncertainties regarding indications and efficacy, the American Society of Clinical Oncology and the American Society of Hematology developed an evidence-based clinical practice guideline for the use of epoetin in patients with cancer. The guideline panel found good evidence to recommend use of epoetin as a treatment option for patients with chemotherapy-associated anemia with a hemoglobin (Hgb) concentration below 10 g/dL. Use of epoetin for patients with less severe anemia (Hgb level below 12 g/dL but never below 10 g/dL) should be determined by clinical circumstances. Good evidence from clinical trials supports the use of subcutaneous epoetin thrice weekly (150 U/kg) for a minimum of 4 weeks. Less strong evidence supports an alternative weekly (40 000 U/wk) dosing regimen, based on common clinical practice. With either administration schedule, dose escalation should be considered for those not responding to the initial dose. In the absence of response, continuing epoetin beyond 6-8 weeks does not appear to be beneficial. Epoetin should be titrated once the hemoglobin concentration reaches 12 g/dL. Evidence from one randomized controlled trial supports use of epoetin for patients with anemia associated with low-risk myelodysplasia not receiving chemotherapy; however, there are no published high-quality studies to support its use for anemia in other hematologic malignancies in the absence of chemotherapy. Therefore, for anemic patients with hematologic malignancies it is recommended that physicians initiate conventional therapy and observe hematologic response before considering use of epoetin.

Topics: Anemia; Clinical Trials as Topic; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Hematinics; Humans; Neoplasms; Quality Assurance, Health Care; Recombinant Proteins

Topics: Anemia; Arthroplasty, Replacement, Hip; Blood Loss, Surgical; Epoetin Alfa; Erythropoietin; Humans; Preoperative Care; Recombinant Proteins

Anemia is a common complication of advancing chronic kidney disease, yet little is known about the consistency of anemia treatment before end-stage renal disease (ESRD) and mortality on dialysis therapy.. We studied 89,193 incident Medicare patients with ESRD in 1995 to 1997 aged 67 plus years with claims 2 years before their dialysis therapy initiation. Patients were classified as follows: no epoetin, 25% or less (least consistent), greater than 25% to 50%, greater than 50% to 75%, and greater than 75% (most consistent) epoetin treatment in the available months from the first pre-ESRD epoetin dose to the first ESRD service date. Cox regression modeled the risk for 1-year death in the post-ESRD period, adjusting for age, sex, race, diabetic status, albumin level, and incidence year.. Sixty percent of patients had hematocrits less than 30% at ESRD initiation, yet only 15.6% (N = 13,877) had epoetin claims before ESRD. The most consistent epoetin treatment group had hematocrits increase from 27.5% to 30.8% (P < 0.0001) by month 4 of treatment. Patients with the most consistent epoetin treatment had a greater mean hematocrit (29.2% +/- 0.11%; P < 0.0001) and albumin level (3.31 +/- 0.01 g/dL [33.1 g/L]) at initiation than those with the least consistent treatment (28.1% +/- 0.10% and 3.21 +/- 0.01 g/dL [32.1 g/L], respectively). The relative risk for death in patients with the least consistent versus the most consistent (the reference) epoetin treatment was 1.460 (95% CI, 1.245 to 1.713; P < 0.0001) 1 year after the first ESRD service date.. Elderly patients with consistent pre-ESRD epoetin treatment had lower risks for death in the first year of dialysis therapy after ESRD initiation.

Topics: Aged; Anemia; Diabetes Complications; Diabetes Mellitus; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Indices; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Male; Models, Statistical; Mortality; Racial Groups; Recombinant Proteins; Renal Dialysis; Reproducibility of Results; Serum Albumin; Sex Factors; Survival Rate

Topics: Anemia; Drug Labeling; Epoetin Alfa; Erythropoietin; Fraud; HIV Infections; Humans; Recombinant Proteins; United States; United States Food and Drug Administration

Topics: Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Research Design

A wide spectrum of clinical data has consistently demonstrated improvements in survival, hospitalization, and other factors affecting quality of life in dialysis patients who maintain hemoglobin levels between 11 and 12 g/dL, and most U.S. dialysis facilities generally target this range for their patients. Recent data indicate that several factors, including time on dialysis, Epoetin alfa dosing practices, peritoneal dialysis modality, younger age, African American race, and some comorbidities, may increase the risk for lower hemoglobin levels. Although additional clinical studies are required to fully define the factors that may contribute to lower hemoglobin levels in these patients, nephrology nurses should be aware of the potential need to modify therapeutic approaches in these subpopulations to ensure that all patients have the opportunity to attain and maintain target hemoglobin levels.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Hemoglobins; Humans; Recombinant Proteins; Renal Dialysis

Chronic kidney disease (CKD) is a growing public health problem. Morbidity and mortality rates from CKD and end-stage renal disease remain high despite the advent of new knowledge, therapies, and clinical practice guidelines. Consequently, the reasons for the underdiagnosis and undertreatment of CKD must be addressed and appropriate preventive and therapeutic interventions implemented. Managed care organizations (MCOs) can facilitate this process by implementing intervention programs that target clinicians and patients with kidney disease. These programs should promote 1) early detection of CKD and comorbid conditions; 2) use of appropriate outcome measures to stratify patient care; 3) implementation of strategies to delay disease progression and prevent or treat complications; and 4) adequate preparation for and timely initiation of renal replacement therapy. Early detection and proactive care of predialysis patients not only improve outcomes and quality of life, but also reduce costs for society and MCOs.

Topics: Anemia; Darbepoetin alfa; Education, Medical, Continuing; Epoetin Alfa; Erythropoietin; Glomerular Filtration Rate; Hematinics; Humans; Kidney Failure, Chronic; Managed Care Programs; Mass Screening; Practice Guidelines as Topic; Preventive Health Services; Quality Assurance, Health Care; Quality Indicators, Health Care; Recombinant Proteins; Renal Dialysis; United States

Topics: Anemia; Animals; Epoetin Alfa; Erythropoietin; Humans; Kidney Failure, Chronic; Recombinant Proteins

This study was undertaken to describe the relationship between hematocrit (Hct) and changes in the prescribed dose of erythropoietin (EPO) as well as selected patient and process care measures across annual national samples of hemodialysis patients from 1994 to 1998. This study uses the cohorts identified in the ESRD Core Indicators Project, random samples of 6181, 6241, 6364, 6634, and 7660 patients, stratified by ESRD Networks drawn for each year from 1994 to 1998. Patient demographic and clinical information was collected from October to December for each year. Surrogates of iron stores and patterns of iron and EPO administration were profiled from 1996 to 1998. Multivariable stepwise linear regression analyses were performed to adjust for potential confounding variables and to identify independent variables associated with Hct and EPO dose. Mean Hct and EPO dose increased each year from 31.1 +/- 5.2% to 34.1 +/- 3.7% and from 58.2 +/- 41.8 U/kg to 68.2 +/- 55.0 U/kg, respectively (P = 0.0001). Increasing Hct was positively associated with male gender, more years on dialysis, older age, higher urea reduction ratio and transferrin saturation, prescription of intravenous iron, and lower ferritin and EPO dose in multivariable models (all P = 0.0001). Male gender, older age, diabetes, higher Hct, and increasing weight, urea reduction ration, and transferrin saturation were associated with lower EPO doses (all P < 0.01). Conversely, intravenous EPO and iron were associated with higher prescribed EPO doses (all P = 0.0001). Although increasing Hct is associated with decreasing EPO dose at the patient level, the increase in Hct seen across years among the cohorts of hemodialysis patients in the United States has been associated with increasing doses of EPO at the population level.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Male; Quality Indicators, Health Care; Recombinant Proteins; Renal Dialysis; Serum Albumin; Transferrin; United States

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

(1) The standard treatment for symptomatic anaemia due to cytotoxic chemotherapy is blood transfusion. (2) The licensing terms for epoetin alfa have been extended to cover the treatment of anaemia induced by all cytotoxic drugs, no longer only by platinum salts. The licensing terms for epoetin beta have been extended to cover some haematological malignancies. (3) The clinical file on epoetin alfa contains data from 8 placebo-controlled double-blind trials in patients with anaemia. Four trials showed a significant reduction (of 12-35%) in the number of patients transfused during the second and third months of treatment with epoetin alfa. (4) Quality of life was mentioned in only two trial reports. In one, the score was significantly better on epoetin alfa than on placebo, but the practical repercussions of this difference are unclear. In the other trial there was no significant difference between the groups. (5) The clinical file on epoetin beta contains data only from unblended dose-finding studies showing a favourable impact on the haemoglobin level and transfusion requirements. (6) The preventive effect of the two epoetins has not been compared with that of alternative treatments. (7) The main known risks of epoetin are arterial hypertension and thrombosis. Stimulation of tumour growth cannot be ruled out. (8) Epoetin beta has a practical advantage, in that it can be stored for a few days at room temperature. (9) In practice, epoetin is the standard treatment of anaemia after chemotherapy, outside emergency situations.

Topics: Anemia; Clinical Trials as Topic; Drug Approval; Epoetin Alfa; Erythropoietin; France; Hematinics; Humans; Neoplasms; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythroblasts; Erythropoietin; Humans; Recombinant Proteins; Renal Insufficiency

Topics: Adverse Drug Reaction Reporting Systems; Anemia; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Red-Cell Aplasia, Pure; United States

Breast cancer patients receiving chemotherapy often exhibit anemia, which contributes to symptoms such as fatigue, compromising quality of life (QOL). The present subset analysis assessed the effects of recombinant human erythropoietin (rHuEPO, epoetin alfa) on anemia and QOL in approximately 1300 patients with breast cancer, who were derived from 3 large, community-based clinical trials of epoetin alfa in anemic chemotherapy patients with various malignancies. Epoetin alfa effectively and safely corrected anemia and improved QOL scores on the Linear Analogue Self-Assessment, which measures energy, ability to perform daily activities, and QOL. Clinical, laboratory, and QOL improvements were qualitatively and quantitatively similar to those reported in the larger populations with various tumor types. The efficacy and safety of epoetin alfa did not vary according to dosing frequency (1 vs. 3 times weekly). Epoetin alfa is, therefore, effective and safe in the management of anemia in patients with breast cancer treated with chemotherapy.

Topics: Anemia; Antineoplastic Agents; Breast Neoplasms; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Female; Humans; Injections, Subcutaneous; Quality of Life; Recombinant Proteins; Retrospective Studies

Recombinant human erythropoietin (rHuEpo) may affect the human immune system. The aim of the study was to examine changes in CD4(+) and CD8(+) T-cell subpopulations, the expression of the inhibitory molecule, CD152 on T lymphocytes and the levels of interleukins (IL) 2, 6, 10, 12 and tumour necrosis factor alpha (TNF alpha) in primary glomerulonephritis chronic haemodialysis (HD) patients before and under rHuEpo treatment.. Expression of T-cell surface molecules was measured in 14 HD patients ex vivo by flow cytometry of lymphocytes sampled from peripheral blood and in vitro using whole blood cell cultures stimulated either with phytohaemagglutinin (PHA) or with physiological as well as non-physiological doses of rHuEpo. The concentrations of the cytokines were measured in the supernatants from non- or PHA-stimulated cultures using bioassays (IL2, IL6, TNF alpha) or ELISA tests (IL10, IL12).. Compared with findings before the start of rHuEpo therapy the CD4(+)/CD8(+) ratio increased after 1 year of follow-up, whereas the percentage of CD152(+) peripheral blood lymphocytes decreased. The increase of the CD4(+)/CD8(+) ratio was dependent on a decrease of the percentage of CD8(+) cells. The decrease of CD152(+) population affected mainly CD8(+)CD152(+) cells. All these effects became apparent after 6 months of rHuEpo treatment. In vitro stimulation of whole blood cultures revealed that the addition of PHA up-regulated the percentage of CD152(+) lymphocytes, while physiological concentrations of rHuEpo decreased the percentage of CD8(+)152(+) T cells. None of the stimuli used affected the percentage of CD8(+) T cells. The pattern of the cytokines shifted toward TH1 phenotype (increase of IL2 and 12 levels) with a decreased level of proinflammatory cytokines (decrease of IL6 and TNFalpha levels).. The observed decrease of CD152(+) lymphocytes together with the decrease of CD8(+) cells may reflect the improved immune response observed in HD patients under rHuEpo treatment.

Topics: Abatacept; Anemia; Antigens, CD; Antigens, Differentiation; CD4-CD8 Ratio; CTLA-4 Antigen; Cytokines; Epoetin Alfa; Erythropoietin; Ferritins; Glomerulonephritis; Hematinics; Humans; Immunoconjugates; Lymphocyte Count; Lymphocytes; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Transferrin

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Research Design

Topics: Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Medical Oncology; Neoplasms; Practice Guidelines as Topic; Quality of Life; Recombinant Proteins; United States; United States Agency for Healthcare Research and Quality

Topics: Anemia; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis

To define the incidence, course, and etiology of hematologic abnormalities in children on tacrolimus-based immunosuppression, we reviewed records of 106 transplant patients (70 heart, 16 heart and lung, 20 double lung), 0-21 yr of age, who were transplanted at the Children's Hospital of Pittsburgh from 1989 to 1997. Fifty-four of the 106 patients (51%) developed 65 abnormal hematologic episodes (32 anemia, nine neutropenia, nine thrombocytopenia, 15 simultaneous anemia and neutropenia with or without thrombocytopenia). Common etiologies included: infections, post-transplant lymphoproliferative disease, and medications. Eleven episodes (seven anemia, one neutropenia, and three simultaneous anemia and neutropenia) had unclear etiologies and process of elimination suggested an association with tacrolimus. Interventions included filgrastim (effective in 15 of 15 patients, with resolution of neutropenia in a median of 5 days) and epoetin alfa (effective in five of 16 patients, including four of four patients with anemia possibly related to tacrolimus). Five patients (two with neutropenia and three with simultaneous neutropenia and anemia) were switched to cyclosporin A (CsA); rapid resolution occurred in four of the five patients, suggesting a possible association of the hematologic abnormalities with tacrolimus. In summary, hematologic abnormalities are common in children on tacrolimus-based immunosuppression. Most of these hematologic abnormalities are caused by common etiologies; however, a sub-population exists where tacrolimus may be the etiologic agent. Anemia and neutropenia respond to treatment with epoetin alfa and filgrastim. After thorough investigation, a trial switch to CsA may be warranted.

Topics: Adolescent; Adult; Anemia; Child; Child, Preschool; Epoetin Alfa; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Heart Transplantation; Heart-Lung Transplantation; Hematologic Diseases; Humans; Immunosuppressive Agents; Infant; Lung Transplantation; Male; Neutropenia; Recombinant Proteins; Retrospective Studies; Tacrolimus; Thrombocytopenia

Topics: Aged; Aged, 80 and over; Anemia; Biopsy; Bone Marrow; Cell Nucleus; Diagnosis, Differential; Epoetin Alfa; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Leukopenia; Multiple Myeloma; Recombinant Proteins

Topics: Algorithms; Anemia; Clinical Protocols; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Patient Care Team; Pharmacists; Program Evaluation; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Statistics, Nonparametric; Transferrin; Treatment Outcome

Anaemia is a common complication of cancer and cancer therapies, and fatigue is one of the most common symptoms of anaemia, disrupting functional performance and reducing overall quality of life. The positive effects of treating renal patients with recombinant human erythropoietin are well documented. This case report series details the specific effects of fatigue on individual patients with cancer and their way of life, and describes their significant improvement in lifestyle following the reversal of anaemia using recombinant human erythropoietin, epoetin alfa.

Topics: Aged; Anemia; Epoetin Alfa; Erythropoietin; Fatal Outcome; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins

The Health Care Financing Administration's End-Stage Renal Disease (ESRD) Core Indicators Project collects clinical information on prevalent adult patients receiving in-center hemodialysis (HD) care in the United States to assess the quality of care delivered. Although hematocrit values, transferrin saturations, and iron prescription practices have improved over the last five years, we sought to determine whether continued opportunities for improvement of this domain of care exist.. A random sample of 7292 adult in-center HD patients was selected. Dialysis facility staff provided clinical information for the period of October through December 1996 for 6858 (94%) patients; complete laboratory information was available from 4991 (73%) returned forms. Hematocrit values, transferrin saturations, serum ferritin concentrations, epoetin alfa dosing, and iron prescriptions were abstracted from patient medical records to assess anemia management practices.. The mean hematocrit for this cohort was 32.6 +/- 3.5%. Seventy-two percent of patients had hematocrit values> 30%. Forty-two percent had hematocrit values of 33 to 36%, and 10% were severely anemic (hematocrit <28%). Ninety-four percent of the patients received epoetin alfa intravenously (i.v.) and 6% subcutaneously. The mean weekly dose was 202.4 +/- 137.2 units/kg. The mean transferrin saturation was 27.4 +/- 12.6%; 73% of patients had a mean transferrin saturation > or = 20%. The mean serum ferritin concentration was 386 +/- 422 ng/mL; 79 and 12% of patients had a serum ferritin concentration of> 100 and> 800 ng/mL, respectively. Nine percent of the sample (N = 434) had a transferrin saturation <20% and serum ferritin concentration <100 ng/mL. Regardless of the patient's transferrin saturation, approximately three fourths of the patients received either oral or i.v. iron, and only approximately one half of the patients received i.v. iron. Of the subset of patients with transferrin saturation <20% and serum ferritin concentration <800 ng/mL, only 53% were prescribed intravenous iron. Multivariate linear regression analysis revealed that serum albumin, urea reduction ratio, age, and transferrin saturation were significantly positively associated with hematocrit. Epoetin alfa dose and serum ferritin concentration were significantly and negatively associated with the hematocrit (P < 0.001).. Although substantial improvements have been made in anemia management for adult in-center HD patients over the past five years, significant opportunities persist to improve iron prescription practices.

Topics: Adult; Aged; Ambulatory Care; Anemia; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Quality Indicators, Health Care; Recombinant Proteins; Renal Dialysis; Serum Albumin; Transferrin; United States

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Treatment Failure

Topics: Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Epoetin Alfa; Erythropoietin; Europe; Evidence-Based Medicine; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Practice Patterns, Physicians'; Quality of Life; Recombinant Proteins; Treatment Outcome; United States

Topics: Anemia; Antineoplastic Agents; Child; Child, Preschool; Epoetin Alfa; Erythropoietin; Humans; Infant; Infant, Newborn; Infant, Premature; Iron; Kidney Failure, Chronic; Neoplasms; Radiotherapy; Recombinant Proteins

Documentation is an integral part of good anemia management. In addition to relaying vital clinical information, documentation demonstrates how nurses and other medical professionals are striving to achieve the standards of care mandated by law, their profession, third party payers, and individual health care providers. Proper documentation of anemia management practices should include a written chronological history of the rationales, plans, interventions, and evaluations initiated to achieve patient-specific Hb/Hct target levels across the spectrum of care.

Topics: Anemia; Documentation; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Middle Aged; Recombinant Proteins

Topics: Anemia; Cost Savings; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Specialties, Nursing

I.v. ascorbic acid has been used in an effort to mobilize ferritin stores in hyporesponsive HD patients receiving Epoetin alfa. However, not all patients who respond to i.v. ascorbic acid therapy will have subsequent decline in feritin stores (Gastaldello et al., 1995; Tarng & Huang, 1998). Additionally, predicting those patients who will overcome their Epoetin alfa hyporesponsiveness remains unclear. Ascorbic acid's effect on hemosiderin deposits may be another possible mechanism to the increased Epoetin alfa response observed in some HD patients (Hemosiderin is a pathologic deposition of iron in tissues including the spleen, small intestine, and bone marrow). Although there are no well-controlled studies evaluating hemosiderin and i.v. ascorbic acid, it should be noted that subjects with scurvy often present with excessive iron deposits in the tissues, indicating the possible effects of ascorbic acid on hemosiderin metabolism (Bothwell et al., 1964). Ascorbic acid deficiency is often present in many HD patients due to its removal during dialysis and lack of dietary intake (Ponka & Kuhlback, 1983). It remains controversial whether oral ascorbic acid supplementation is indicated in patients receiving HD. Therefore, the Recommended Daily Allowance (RDA) of 60 mg/day should be advised (Makoff, 1999). I.v. ascorbic acid should be considered as a possible adjuvant to therapy in patients who are "iron-overloaded" and hyporesponsive to Epoetin alfa. Although the long-term effects of i.v. ascorbic acid on HD patients is unknown, the potential risk of secondary oxalosis should be considered (Costello, 1991; Pru, Eaton, & Kjellstrand, 1985). It may be necessary to monitor plasma oxalate levels if long-term therapy with i.v. ascorbic acid is used. Clinical studies have examined i.v. ascorbic acid doses from 300 mg-500 mg given up to TIW for a maximum duration of 12 weeks without any significant deleterious effects (Gastaldello et al., 1995; Tarng & Huang, 1998; Tarng et al., 1999). However, large-scale, prospective, and controlled trails are needed to determine the long-term safety and efficacy of i.v. ascorbic acid therapy in iron overloaded HD patients receiving Epoetin alfa.

Topics: Anemia; Antioxidants; Ascorbic Acid; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins

Because anemia is associated with reduced long-term survival, and because allogeneic transfusion is linked to increased recurrence of disease and reduced rates of long-term survival, alternative options for managing anemia in the orthopedic oncologic patient have been sought. Managing the anemia of cancer is particularly challenging given the many obstacles to employing conventional blood management options. One potential means of treating perioperative anemia in orthopedic oncologic patients involves the use of Epoetin alfa. The clinical utility of Epoetin alfa in this setting, however, must be determined in controlled trials.

Topics: Anemia; Blood Loss, Surgical; Blood Transfusion, Autologous; Bone Neoplasms; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins; Recurrence; Transfusion Reaction

Carnitor use for carnitine deficiency in chronic renal failure is a multidisciplinary management issue. This medication and its usefulness needs require further nursing investigation.

Topics: Aged; Aged, 80 and over; Anemia; Carnitine; Drug Resistance; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Male; Nursing Diagnosis; Recombinant Proteins; Renal Dialysis

The HCFA ESRD Core Indicators Project is designed to assess several key indicators of care in peritoneal dialysis patients, including anemia management. Information on hematocrit levels, epoetin alfa dosing, estimates of iron stores, and iron therapy as obtained in a national sample of 1,219 peritoneal dialysis patients are described. The average hematocrit was 32.8% +/- 3.8%, and severe anemia (hematocrit < 25%) occurred in 1.4% of PD patients. The mean weekly epoetin alfa dose was 134.6 U/kg. In general, there was an inverse relationship between hematocrit and epoetin alfa doses. Most (83%) of PD patients received iron therapy, with only 8% of patients receiving intravenous iron. The mean serum ferritin was 303 ng/mL, with 64% of patients having a ferritin greater than 100 ng/mL. The mean transferrin saturation was 28%, with 60% of patients having a value of less than 20%. There was an inverse relationship between serum ferritin levels and hematocrit but no relationship between hematocrit and transferrin. It is concluded that there could be improvement in the epoetin alfa and iron management in many patients.

Topics: Adolescent; Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Recombinant Proteins; Transferrin

Topics: Anemia; Antineoplastic Agents; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Treatment of metastatic melanoma with biochemotherapy results in the rapid onset of anemia, requiring blood transfusion in 9 of 13 (69%) patients. Prophylactic use of weekly subcutaneous recombinant epoetin alfa eliminated the need for transfusion in all but 1 of 21 (5%) patients.

Topics: Anemia; Blood Transfusion; Cost-Benefit Analysis; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Melanoma; Neoplasm Metastasis; Quality of Life; Recombinant Proteins

Topics: Activities of Daily Living; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Orthopedics; Preoperative Care; Randomized Controlled Trials as Topic; Recombinant Proteins; Transfusion Reaction; Treatment Outcome

Epoetin alfa is being used to treat patients with symptomatic anemia of cancer and to prevent or postpone chemotherapy-induced anemia in cancer treatment. As only approximately 50% of unselected anemic cancer patients respond sufficiently to epoetin alfa treatment, careful patient selection according to reliable prediction criteria is of great importance. Predictions of response to epoetin alfa treatment are based either on the degree of blunted erythropoietin response to the anemic condition or on indicators of responsiveness during the early treatment phase. The most accurate predictions of responsiveness, however, are derived from combinations of predictive factors. Combinations of synergistically acting hematopoietic growth factors, particularly epoetin alfa and granulocyte colony-stimulating factor, are beneficial to selected patients with myelodysplastic syndrome and may prolong survival in certain cases. Correction of anemia in cancer patients is particularly important because highly significant correlations have been reported between hemoglobin levels and quality of life in these patients.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Myelodysplastic Syndromes; Neoplasms; Patient Selection; Quality of Life; Recombinant Proteins

Even with the reservations that exist regarding the accuracy of tools to measure quality of life, there is little doubt that epoetin has dramatically improved the quality of life in patients with the anemia of chronic renal failure. Patients feel better and have increased energy levels, greater capacity for physical exercise, fewer symptoms of lethargy and tiredness, improved memory and concentration, and less angina and breathlessness. Cardiac, sexual, and cognitive functions all improve, and quality of life assessments suggest enhancements in both physical and social aspects of well-being. Furthermore, circumstantial evidence suggests that treatment with epoetin is quite likely to reduce cardiovascular morbidity and mortality in patients with renal anemia. While chronic anemia has common characteristics irrespective of the etiology, the implications on quality of life in patients with chronic renal failure vary in a number of ways from those in patients with cancer.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms; Quality of Life; Recombinant Proteins

High-dose chemotherapy (HDCT) with bone marrow transplantation (BMT) is associated with the development of significant anemia. The anemia is caused mainly by myelosuppression, although gastrointestinal-, genitourinary-, and phlebotomy-induced blood loss may also contribute. The number of red blood cell units transfused during the first 30 days following HDCT depends on the chemotherapy used, the underlying disease, and whether BMT was allogeneic, autologous, and used either peripheral blood stem cell or bone marrow support. Epoetin alfa has been used to treat the anemia that develops in the HDCT setting. Controlled studies in patients with both hematologic malignancies and solid tumors who were given epoetin alfa following HDCT have shown that red blood cell transfusion requirements decrease in patients receiving allogeneic BMT. Results using epoetin alfa in patients receiving autologous BMT have been disappointing. Alternatively, combination therapy with granulocyte colony-stimulating factor and epoetin alfa has been effective in mobilizing stem cell and committed myeloid/erythroid precursors before HDCT, but has not resulted in a lower red blood cell transfusion requirement after HDCT. Administration of epoetin alfa before HDCT while the bone marrow is still responsive to growth factors may be a new strategy with which to decrease the anemia in this setting.

Topics: Anemia; Antineoplastic Agents; Bone Marrow Transplantation; Epoetin Alfa; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Neoplasms; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Due to the increased risks associated with allogenic blood transfusion, blood management in surgical procedures, especially in orthopedic settings, should include reduction of perioperative blood loss. Preoperative nursing assessment will help define patients at increased risk for transfusion. Both nonpharmacologic and pharmacologic techniques can help minimize allogenic transfusion by reducing blood loss. One such method of managing anemia and reducing patient exposure to allogenic transfusion is the perioperative use of recombinant human erythropoietin--erythropoietin alfa--an innovative surgical blood management tool. Increased awareness by perioperative nurses of the use of erythropoietin alfa and patient implications can contribute to the overall blood conservation goal.

Topics: Anemia; Anesthesia, Epidural; Blood Loss, Surgical; Blood Transfusion; Christianity; Contraindications; Elective Surgical Procedures; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Operating Rooms; Perioperative Nursing; Recombinant Proteins; Treatment Refusal; United States

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Infant; Male; Recombinant Proteins; Skull

The cost-effectiveness impact of iron dextran administration on the use of epoetin alfa and blood in hemodialysis patients was studied. Subjects were ambulatory hemodialysis patients who had been receiving hemodialysis for at least six months before the start of an iron dextran protocol and who had been given epoetin alfa for at least four of those six months. Clinical data were collected for six months before and six months after the protocol was implemented. Successful treatment was defined as a hematocrit of 33-36%, a transferrin saturation of >10%, a ferritin concentration of >100 ng/mL, and no blood use except for acute blood loss. A total of 33 patients completed the study. Fifty units of blood were used in the first six months and nine units in the second six months. There was significant improvement in mean hematocrit, ferritin, and transferrin saturation values after the protocol began. Average epoetin alfa doses did not change significantly. There was significant improvement in success rates for ferritin and blood use and in the overall success rate. Ten patients met all success criteria in the preprotocol period, versus 27 in the postprotocol period. Monthly cost-effectiveness analysis for the preprotocol and postprotocol periods indicated costs of $1350 and $526, per successful treatment, respectively. The incremental cost-effectiveness of iron dextran was $42 per successful treatment. Iron dextran improved iron indices and reduced the need for blood transfusions but did not reduce the average dose of epoetin alfa. The additional cost of therapy per month seemed justified by the clinical benefits.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hematocrit; Humans; Idaho; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Transferrin

Guidelines for the treatment of anemia in chronic renal failure (CRF) patients were recently published by NKF-DOQI. The background was provided by the fact that anemia in CRF patients fulfills all the criteria requested for the outlining of guidelines. In fact: 1) anemia is a clinically relevant problem for CRF patients; 2) it may be prevented by adequate erythropoietin (EPO) therapy; 3) a great variability in its management exists, not only concerning the optimal hematocrit (HCT) level, but also the treatment schedule as well as iron supplementation. More than eight hundred forty five scientific articles were retrieved in full text, eventually leading to 530 structurally reviewed papers (349 cited in the final text) thus providing the basis for the strength of recommendations (evidence or opinions): all topics were subdivided into 7 main issues (diagnostic and therapeutic). Main results were the following: HCT, hemoglobin (Hb), red blood cell, serum iron binding capacity, percent transferrin saturation (TSAT) and serum ferritin (FERR), to evaluate the degree of anemia and iron status; HCT 33 to 36% and Hb 11 to 12 g/dl as possible target levels; TSAT >20% and FERR >100 ug/dl as acceptable lower values for iron status; oral iron administration not <200 mg/day of elemental iron and intravenous iron 50-100 mg/week or 500-100 mg/month (for patients on predialysis or peritoneal dialysis) as therapeutic schedules; subcutaneous route for EPO administration at 80-120 U/kg body weight/week as starting doses. Some issues may be debatable, such as, the underestimation of dialysis efficacy among the causes of inadequate response to EPO as well as the risk of thrombosis among the possible side effects of EPO therapy, or the lack of recommendation for upper limits of FERR values. However, this exhaustive study is an important demonstration of efforts to improve the quality of care in CRF patients.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Italy; Kidney Failure, Chronic; Peritoneal Dialysis; Practice Guidelines as Topic; Quality Assurance, Health Care; Recombinant Proteins; Renal Dialysis

To study the impact of Procrit (epoetin alfa; Amgen Inc, Thousand Oaks, CA) on quality of life, transfusion requirements, and hemoglobin in anemic cancer patients receiving chemotherapy.. More than 500 community-based oncologists enrolled 2,342 patients with malignancies undergoing cytotoxic chemotherapy in an open-label study. Patients were treated with epoetin alfa 150 U/kg three times weekly, which could be doubled if the therapuetic response was judged inadequate. Total treatment was up to 4 months.. Of the 2,342 patients enrolled, data were available for 2,030 patients. Of the 2,030, 1,047 patients completed all 4 months of epoetin alfa therapy. Epoetin alfa was associated with significant increases in mean self-rated scores for energy level, activity level, and overall quality of life; these improvements correlated with the magnitude of the hemoglobin increase and were independent of tumor response. In addition, epoetin alfa was associated with a significant increase in mean hemoglobin and with a significant decrease in the proportion of patients requiring transfusions (baseline to final value, P < .001). Epoetin alfa was well tolerated.. Epoetin alfa is effective in improving the functional status and quality of life in anemic cancer patients receiving chemotherapy, as well as increasing hemoglobin level and decreasing transfusion requirements. Improvement in functional status can be attributed to an increase in hemoglobin level, demonstrating that quality of life in this group of patients can be improved by aggressively treating anemia. Further studies will be required to define the optimal doses and schedules for epoetin alfa.

Topics: Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Humans; Iron; Kidney Failure, Chronic; Recombinant Proteins

Topics: Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Recombinant Proteins; Treatment Outcome

Topics: Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematinics; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Recombinant Proteins

Topics: Anemia; Animals; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Kidney Failure, Chronic; Recombinant Proteins

Anemia is best managed with an effective protocol that provides standardized guidance for clinical interventions while maintaining the flexibility to respond to the needs of individual patients. An anemia management protocol can help nurses and other clinicians: (a) monitor and manage erythropoietic parameters, (b) successfully achieve the higher hematocrit (33% to 36%) and hemoglobin (11 g/dL to 12 g/dL) target levels recommended by the Dialysis Outcomes Quality Initiative (DOQI) guidelines, and (c) maintain a stable Hct to help manage the new Medicare Hematocrit Measurement Audit policy. Maintaining a stable hematocrit higher in the target range has been associated with improved patient outcomes. This article describes how to use a continuous quality improvement (CQI) approach to develop an anemia management protocol. The potential benefits of coordinating protocol implementation through an anemia management nurse are also discussed.

Topics: Anemia; Clinical Protocols; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Monitoring, Physiologic; Outcome Assessment, Health Care; Recombinant Proteins

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Breast Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Female; Humans; Middle Aged; Neoplasms; Recombinant Proteins; Risk Assessment

Autologous blood (AB) donation can minimize exposure to allogeneic blood in patients scheduled for coronary artery bypass graft (CABG) surgery. During AB donation in this group of patients, minimization of the accompanying decrease in hemoglobin (Hb) levels is important to reduce the risk of provoking silent myocardial ischemia and/or arrhythmias. Recombinant human erythropoietin (rHuEPO) has been used to facilitate AB donation and minimize the accompanying decrease in Hb levels in patients scheduled for cardiac surgery. In 24 patients scheduled for CABG surgery, once-weekly subcutaneous (s.c.) administration of rHuEPO (epoetin alfa 400 IU/kg) plus oral iron supplementation for 4 weeks prior to surgery caused marked stimulation of erythropoiesis and significantly increased collection of autologous red blood cells (RBCs) compared with oral iron alone. Furthermore, epoetin alfa minimized the decrease in Hb levels associated with AB donation and significantly attenuated allogeneic blood requirements by facilitating the collection of 4 AB units prior to surgery. During AB donation, no changes in the incidence or severity of ischemic attacks or ST-segment changes were observed using electrocardiographic monitoring. Epoetin alfa was well tolerated. Once-weekly s.c. administration of epoetin alfa for 4 weeks therefore represents a practical means of facilitating AB donation by patients scheduled for CABG surgery.

Topics: Anemia; Blood Transfusion, Autologous; Coronary Artery Bypass; Elective Surgical Procedures; Epoetin Alfa; Erythropoiesis; Erythropoietin; Ferrous Compounds; Hemodilution; Hemoglobins; Humans; Injections, Subcutaneous; Male; Premedication; Recombinant Proteins; Treatment Outcome

Topics: Anemia; Blood Transfusion; Blood Transfusion, Autologous; Cardiac Surgical Procedures; Contraindications; Elective Surgical Procedures; Epoetin Alfa; Erythropoietin; Female; Hematocrit; Humans; Male; Premedication; Recombinant Proteins; Time Factors

We hypothesize that reduced sympathetic stimulation of erythropoietin production may maintain the anemia which develops in virtually all space travellers. We tested this hypothesis in a human model of reduced sympathetic activity. Thirty-three patients with the Bradbury-Eggleston syndrome were divided into three groups according to their hemoglobin (Hgb) level. Patients with low Hgb had lower upright norepinephrine and lower upright renin. Patients with anemia also had inappropriately low plasma erythropoietin levels. We administered recombinant erythropoietin (Epogen) 25-50 units/kg s.c. 3 times per week and found that the anemia seen in autonomic failure could be reversed by this treatment. These results support the hypothesis that erythropoiesis is modulated by the sympathetic nervous system and that at such mechanisms may also operate in the microgravity environment where sympathetic activity is reduced.

Topics: Anemia; Catecholamines; Epoetin Alfa; Erythrocyte Volume; Erythropoiesis; Erythropoietin; Humans; Hypotension, Orthostatic; Posture; Recombinant Proteins; Renin; Space Flight; Sympathetic Nervous System; Weightlessness

Topics: Adaptation, Physiological; Altitude; Anemia; Biochemical Phenomena; Biochemistry; Epoetin Alfa; Erythropoietin; Hypoxia; Iron Isotopes; Kidney; Phenylhydrazines; Rats; Research; Serum Albumin; Serum Albumin, Radio-Iodinated

Topics: Anemia; Animals; Blood; Epoetin Alfa; Erythropoietin; Haplorhini; Infarction; Ischemia; Kidney Transplantation; Macaca mulatta; Nephrectomy; Research; Thrombosis; Transplantation, Autologous; Uremia

Topics: Anemia; Animals; Callitrichinae; Epoetin Alfa; Erythropoietin; Estrogens; Haplorhini; Hypoxia; Nephrectomy; Pharmacology; Research; Testosterone

Topics: Anemia; Animals; Callitrichinae; Epoetin Alfa; Erythropoietin; Haplorhini; Hypoxia; Research; Saguinus

Topics: Anemia; Animals; Blood Chemical Analysis; Cobalt; Electrophoresis; Enzymes; Epoetin Alfa; Erythropoietin; Iron Isotopes; Isoenzymes; Kidney; L-Lactate Dehydrogenase; Lagomorpha; Metabolism; Oxygen; Pharmacology; Rabbits; Research

Following the successful replacement of diseased kidneys by renal homotransplants, regression of the anemia of chronic renal disease was found in five patients. Increased erythropoietic-stimulating activity was demonstrated in the serum of one patient seven weeks after renal transplantation when he suffered a severe hemorrhage. It is postulated that a renal homotransplant can produce enough erythropoietin to maintain a normal hemoglobin value and to respond to the stimulus of a sudden hemorrhage.

Topics: Anemia; Epoetin Alfa; Erythrocyte Count; Erythropoiesis; Erythropoietin; Hemoglobins; Hemorrhage; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Male; Postoperative Complications; Reticulocytes; Transplantation, Homologous

Topics: Anemia; Epoetin Alfa; Erythropoiesis; Erythropoietin; Iron; Iron Isotopes; Protein Deficiency; Rats; Research

Topics: Anemia; Animals; Epoetin Alfa; Erythrocyte Count; Erythropoietin; Hemoglobinometry; Hemolysis; Mice; Phenylhydrazines; Physiology; Polycythemia; Rabbits; Research; Toxicology

Topics: Anemia; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Pernicious; Blood Coagulation; Blood Proteins; Chloramphenicol; Epidemiology; Epoetin Alfa; Erythropoietin; Haptoglobins; Hematologic Diseases; Hematology; Hemochromatosis; Humans; Iron-Dextran Complex; Leukemia; Polycythemia; Thromboplastin; Vitamin B 12

Topics: Anemia; Animals; Bone Marrow; Bone Marrow Cells; Carbon Isotopes; Epoetin Alfa; Erythropoietin; Glycine; Heme; In Vitro Techniques; Lagomorpha; Proteins; Rabbits; Research

Topics: Anemia; Anemia, Aplastic; Anemia, Pernicious; Epoetin Alfa; Erythropoietin; Humans; Polycythemia Vera; Saliva; Splenectomy

Topics: Anemia; Blood Chemical Analysis; Epoetin Alfa; Erythropoietin; Hematinics; Intestine, Small; Intestines; Postgastrectomy Syndromes; Surgical Procedures, Operative; Urine; Vitamin B 12

Topics: Anemia; Animals; Bone Marrow Transplantation; Epoetin Alfa; Erythropoietin; Phenylhydrazines; Plasma; Rabbits; Radiation Injuries; Radiation Injuries, Experimental; Rats; Research

Topics: Anemia; Animals; Blood Volume; Bone Marrow Cells; Chromium Isotopes; Dogs; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hypoxia; Iron Isotopes; Kidney; Nephrectomy; Research; Sheep; Uremia; Ureter

Topics: Anemia; Anemia, Aplastic; Blood Transfusion; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Leukemia; Leukemia, Lymphoid; Metabolism

Topics: Anemia; Body Fluids; Chemistry Techniques, Analytical; Epoetin Alfa; Erythropoietin; Humans; Tracheophyta; Urine

Topics: Anemia; Body Fluids; Epoetin Alfa; Erythrocytes; Erythropoietin; Iron Isotopes; Polycythemia; Rats; Research; Reticulocytes; Urine

Topics: Anemia; Anemia, Hemolytic; Cell Division; DNA; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hemoglobins; Metabolism; Proteins; Reticulocytes; RNA; RNA, Messenger

Topics: Anemia; Anemia, Hypochromic; Anemia, Iron-Deficiency; Anemia, Macrocytic; Blood Platelets; Bone Marrow Cells; Drug Therapy; Epoetin Alfa; Erythropoietin; FIGLU Test; Folic Acid; Folic Acid Deficiency; Glutamates; Hemoglobins; Humans; Infant; Infusions, Parenteral; Injections, Intravenous; Iron; Iron-Dextran Complex; Megakaryocytes; Reticulocytes; Thrombocytopenia; Thrombocytosis; Vitamin B 12

Topics: Anemia; Animals; Bone Marrow Cells; Epoetin Alfa; Erythropoietin; Hemorrhage; In Vitro Techniques; Iron; Polycythemia; Rabbits; Research; Reticulocytes; Sheep; Stem Cells; Tritium

Topics: Anemia; Anemia, Hemolytic; Animals; Biomedical Research; Bone and Bones; Bone Marrow; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematocrit; Hemoglobinometry; Hemorrhage; Humans; Iron Isotopes; Liver; Male; Pharmacology; Phenylhydrazines; Physiology, Comparative; Rabbits; Rats; Research; Spleen

Topics: Alpha-Globulins; Anemia; Antibodies; Biological Assay; Blood; Cerebellar Neoplasms; Electrophoresis; Epoetin Alfa; Erythropoiesis; Erythropoietin; Exudates and Transudates; Hemangiosarcoma; Humans; Hypoxia; Immune Sera; Kidney; Kidney Diseases, Cystic; Leukemia; Leukemia, Lymphoid; Neuraminidase; Trypsin

Topics: Adrenocorticotropic Hormone; Anemia; Basal Metabolism; Epoetin Alfa; Erythrocytes; Erythropoiesis; Erythropoietin; Growth Hormone; Hormones; Human Growth Hormone; Hydrocortisone; Hypophysectomy; Pharmacology; Pituitary Hormones, Anterior; Polycythemia; Rats; Research; Thyrotropin; Thyroxine; Urine

Topics: Anemia; Anemia, Aplastic; Animals; Biological Assay; Epoetin Alfa; Erythropoietin; Haplorhini; Hypoxia; Injections, Intraperitoneal; Iron Isotopes; Kidney; Mice; Nephrectomy; Pharmacology; Physiology, Comparative; Polycythemia; Rabbits; Radiometry; Research; Urine

Topics: Acetylcholinesterase; Alkaline Phosphatase; Anemia; Anemia, Hemolytic; Anticoagulants; Australia; Blood Transfusion; Chromium Isotopes; Coombs Test; Dextrans; Diagnosis, Differential; Drug Therapy; Epoetin Alfa; Erythrocyte Count; Erythrocytes; Erythropoietin; Hematologic Tests; Hemoglobinuria; Hemoglobinuria, Paroxysmal; Hemosiderin; Humans; Iron; Iron Isotopes; Phenindione; Prednisone; Splenectomy; Waldenstrom Macroglobulinemia

Topics: Anemia; Animals; Animals, Newborn; Bloodletting; Epoetin Alfa; Erythropoietin; Rats; Research

Topics: Anemia; Basal Metabolism; Dextrans; Dogs; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematocrit; Physiology; Research; Reticulocytes; Spirometry; Thyroid Function Tests

Topics: Anemia; Anemia, Hemolytic; Antineoplastic Agents; Cytostatic Agents; Epoetin Alfa; Erythropoiesis; Erythropoietin; Pharmacology; Rats; Research; Triaziquone

Topics: Anemia; Animals; Eating; Epoetin Alfa; Erythropoiesis; Erythropoietin; Radiation Injuries; Radiation Injuries, Experimental; Research; Strontium Isotopes; Swine; Swine, Miniature; Toxicology

Topics: Anemia; Anemia, Hemolytic; Animals; Biomedical Research; Bone Marrow; Bone Marrow Examination; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Iron Isotopes; Male; Phenylhydrazines; Rabbits; Radiography; Radioisotopes; Radionuclide Imaging; Rats; Research; Skeleton

Topics: Anemia; Biological Assay; Cobalt; Epoetin Alfa; Erythropoietin; Humans; Hypophysectomy; Hypoxia; Oxygen; Starvation

Topics: Abscess; Anemia; Animals; Epoetin Alfa; Erythropoietin; Hypoxia; Rats; Turpentine

Topics: Anemia; beta-Thalassemia; Epoetin Alfa; Erythroblasts; Erythropoietin; Humans; Protein Deficiency

Topics: Anemia; Anemia, Aplastic; Cerebellar Neoplasms; Epoetin Alfa; Erythropoietin; Hemangiosarcoma; Kidney; Kidney Diseases, Cystic; Radiation Effects; Radiation, Ionizing

Topics: Anemia; Animals; Cattle; Cattle Diseases; Epoetin Alfa; Erythropoietin; Iron

Topics: Acute Kidney Injury; Anemia; Epoetin Alfa; Erythropoietin; Humans; Renal Insufficiency

Topics: Anemia; Blood Chemical Analysis; Bone Marrow; Dietary Proteins; Epoetin Alfa; Erythrocytes; Erythropoietin; Hemoglobins; Hemolysis; Iron; Iron Isotopes; Liver; Phenylhydrazines; Protein Deficiency; Rats; Research; Reticulocytes

Topics: Anemia; Anemia, Aplastic; Blood Chemical Analysis; Body Fluids; Epoetin Alfa; Erythropoietin; Humans; Leukemia; Urine

Topics: Anemia; Animals; Bone Marrow; Culture Media; Epoetin Alfa; Erythropoietin; Humans; Kidney Diseases; Rabbits; Research; Tissue Culture Techniques

After hypertransfusion, normal ww and anemic WW(T) mice show the same increase in red-cell volume, decrease in reticulocytes, and temporary cessation of blood formation. The time required for the red cell volume to return to the value observed before treatment is the same for both groucps of inice. The cell volume at which new erythrocytes are again released into the circulation depends upon the genotype of functioning blood-forming tissue. Injections of erythropoietin stimulate red cell formation in polycythemic ww mice, but have much less (if any) effect upon polycythemic WW(T) mice.

Topics: Anemia; Animals; Epoetin Alfa; Erythrocyte Count; Erythrocytes; Erythropoiesis; Erythropoietin; Homeostasis; Mice; Polycythemia; Research; Reticulocytes

Topics: Anemia; Anemia, Aplastic; Aorta; Cell Division; Epoetin Alfa; Erythropoietin; Humans; Leukemia; Metabolism

Topics: Anemia; Biomedical Research; Blood Chemical Analysis; Bone and Bones; Bone Marrow; Epoetin Alfa; Erythropoietin; Hematopoiesis; Hydroxylamines; Iron; Iron Isotopes; Pharmacology; Physiology; Rats; Research

Topics: Anemia; Animals; Biological Assay; Epoetin Alfa; Erythropoietin; Guinea Pigs; Hematocrit; Hypoxia; Iron Isotopes; Pharmacology; Phenylhydrazines; Polycythemia; Rabbits; Research

Topics: Anemia; Anemia, Hemolytic; Bone Marrow Examination; Epoetin Alfa; Erythrocytes; Erythropoietin; Hematology; Humans; Infant; Infant, Newborn; Metabolism; Physiology

Topics: Anemia; Anemia, Hypochromic; Epoetin Alfa; Erythrocytes; Erythropoietin; Hematologic Diseases; Humans

Topics: Anemia; Epoetin Alfa; Erythrocytes; Erythropoietin; Hematologic Diseases; Hematopoiesis; Humans; Hypoxia

Topics: Anemia; Anemia, Aplastic; Bone Marrow; Epoetin Alfa; Erythrocytes; Erythropoietin; Humans

Topics: Anemia; Bone Marrow; Epoetin Alfa; Erythrocytes; Erythropoietin; Humans; In Vitro Techniques

Topics: Anemia; Animals; Epoetin Alfa; Erythrocytes; Erythropoietin; Hematopoiesis; Rats; Uremia

Topics: Anemia; Anemia, Hemolytic; Anemia, Sickle Cell; Epoetin Alfa; Erythroblastosis, Fetal; Erythrocytes; Erythropoietin; Humans; Infant, Newborn

Topics: Anemia; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans