ferric-carboxymaltose and Inflammatory-Bowel-Diseases

To review the pharmacology, efficacy, and safety of ferric maltol (FM), an oral iron formulation, for iron deficiency anemia (IDA).. A MEDLINE/PubMed and EMBASE (January 1, 1985, to June 19, 2020) literature search was performed using the terms. English language literature evaluating FM pharmacology, pharmacokinetics, efficacy, or safety in the treatment of IDA were reviewed.. FM is a ferric, non-salt-based oral iron formulation demonstrating improved tolerance in patients with previous intolerance to other iron formulations. Phase 3 trials demonstrated significant improvements in anemia and serum iron parameters in patients with inflammatory bowel disease (IBD) and chronic kidney disease (CKD). Common adverse effects were gastrointestinal intolerance.. FM is an effective and well-tolerated alternative to oral iron salts for patients with IBD or CKD and IDA. Emerging data suggest that FM is noninferior to intravenous (IV) ferric carboxymaltose in patients with IBD and IDA. Prior to selecting FM over IV iron products, consideration should be given to time to normalization of Hb, ease of administration, cost, and tolerability.. FM is a relatively safe, effective oral iron therapy that may be better tolerated than other oral iron formulations. FM may be an effective alternative to IV iron in patients with IBD.

Topics: Administration, Intravenous; Administration, Oral; Adult; Anemia, Iron-Deficiency; Clinical Trials as Topic; Female; Ferric Compounds; Hematinics; Humans; Inflammatory Bowel Diseases; Male; Maltose; Pyrones; Renal Insufficiency, Chronic; Treatment Outcome

Intravenous ferric carboxymaltose (Ferinject

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Chronic Disease; Female; Ferric Compounds; Heart Failure; Humans; Inflammatory Bowel Diseases; Kidney Diseases; Maltose; Neoplasms; Postpartum Period; Pregnancy; Treatment Outcome; Uterine Hemorrhage

Iron deficiency (ID) and anemia of chronic diseases (ACD) are the most common causes of anemia in inflammatory bowel disease (IBD), and frequently coexist. In these circumstances, detection of ID may be difficult as inflammation influences the parameters of iron metabolism. The prevalence of iron deficiency anemia (IDA) ranges between 36% and 76% in this population of patients. Anemia may impair physical condition, quality of life (QOL), and cognitive function, negatively affecting almost every aspect of daily life. Furthermore, it may be one of the causes of death in IBD. Consequently, iron replacement therapy should be initiated as soon as ID or IDA is detected, together with the treatment of underlying inflammation. Oral iron therapy is a simple and cheap treatment, but often is poorly tolerated and may worsen the intestinal damage. Moreover, in inflammatory states, duodenal iron absorption is blocked by a cytokine-mediated mechanism. Consequently, intravenous iron therapy is preferred in the presence of severe anemia, intolerance or lack of response to oral iron, and moderately to severely active disease. Recently, new intravenous iron compounds (iron carboxymaltose, iron isomaltoside 1000, ferumoxytol) have become available. Iron carboxymaltose has been shown to be safe and effective in IBD patients with IDA. Furthermore, it allows for rapid administration of high single doses, saving time and costs. If proven to be efficacious and well tolerated, it may become the standard therapy in the near future.

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Clinical Trials as Topic; Ferric Compounds; Humans; Inflammatory Bowel Diseases; Maltose; Quality of Life

Anemia and iron deficiency anemia are very common in inflammatory bowel disease (IBD). In most cases, anemia is a consequence of mixed pathogenesis; inflammation and iron deficiency being the most important factors. Iron status should be evaluated carefully, as ferritin is unreliable in the presence of inflammation. It is always necessary to control disease activity; however, supplementation is usually required to fully correct iron deficiencies. Oral iron, intravenous iron, erythropoietin, and blood transfusions can be used in different clinical scenarios. Oral iron may be used in mild cases if the disease has no clinical activity. Intravenous iron should be preferred where oral iron is poorly tolerated or where it has failed in moderate to severe anemia, and in combination with erythropoietin. Iron sucrose is very safe and effective, but not very convenient, as the total needed dose must be divided into several infusions. Ferric carboxymaltose is much more convenient, and has been shown to be more effective than iron sucrose in a large randomized trial. Iron isomaltose shows theoretical promise, but very limited data are available from IBD populations. Blood transfusion can be necessary, especially in acute life-threatening situations, but the trigger for indication should be in the low range. With the correct use of available resources, anemia and iron deficiency should be well controlled in practically all IBD patients.

Topics: Anemia, Iron-Deficiency; Animals; Ferric Compounds; Humans; Inflammatory Bowel Diseases; Iron; Maltose

Iron deficiency anemia (IDA) frequently occurs in patients suffering from inflammatory bowel disease (IBD) and negatively impacts their quality of life. Nevertheless, the condition appears to be both under-diagnosed and undertreated. Regular biochemical screening of patients with IBD for anemia by the gastroenterology community has to be advocated. Oral iron is a low cost treatment however its effectiveness is limited by low bioavailability and poor tolerability. Intravenous (IV) iron rapidly replenishes iron stores and has demonstrated its safe use in a number of studies in various therapeutic areas. A broad spectrum of new IV iron formulations is now becoming available offering improved tolerability and patient convenience by rapidly restoring the depleted iron status of patients with IBD. The following article aims to review the magnitude of the problem of IDA in IBD, suggest screening standards and highlight existing and future therapies.

Topics: Algorithms; Anemia, Iron-Deficiency; Clinical Trials as Topic; Diagnosis, Differential; Disaccharides; Dose-Response Relationship, Drug; Ferric Compounds; Ferric Oxide, Saccharated; Ferrosoferric Oxide; Glucaric Acid; Hematinics; Humans; Inflammatory Bowel Diseases; Infusions, Intravenous; Iron Deficiencies; Maltose; Prevalence; Thrombocytosis; Thromboembolism

The prevalence of anemia across studies on patients with inflammatory bowel disease (IBD) is high (30%). Both iron deficiency (ID) and anemia of chronic disease contribute most to the development of anemia in IBD. The prevalence of ID is even higher (45%). Anemia and ID negatively impact the patient's quality of life. Therefore, together with an adequate control of disease activity, iron replacement therapy should start as soon as anemia or ID is detected to attain a normal hemoglobin (Hb) and iron status. Many patients will respond to oral iron, but compliance may be poor, whereas intravenous (i.v.) compounds are safe, provide a faster Hb increase and iron store repletion, and presents a lower rate of treatment discontinuation. Absolute indications for i.v. iron treatment should include severe anemia, intolerance or inappropriate response to oral iron, severe intestinal disease activity, or use of an erythropoietic stimulating agent. Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profiles: iron gluconate and iron sucrose (lower single doses), and iron dextran and ferric carboxymaltose (higher single doses). After the initial resolution of anemia and the repletion of iron stores, the patient's hematological and iron parameters should be carefully and periodically monitored, and maintenance iron treatment should be provided as required. New i.v. preparations that allow for giving 1000-1500 mg in a single session, thus facilitating patient management, provide an excellent tool to prevent or treat anemia and ID in this patient population, which in turn avoids allogeneic blood transfusion and improves their quality of life.

Topics: Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Gluconates; Humans; Inflammatory Bowel Diseases; Infusions, Intravenous; Injections, Intraventricular; Iron; Iron-Dextran Complex; Maltose; Treatment Outcome

To determine whether intravenous (IV) or oral iron suppletion is superior in improving physical fitness in anemic children with inflammatory bowel disease (IBD).. We conducted a clinical trial at 11 centers. Children aged 8-18 with IBD and anemia (defined as hemoglobin [Hb] z-score < -2) were randomly assigned to a single IV dose of ferric carboxymaltose or 12 weeks of oral ferrous fumarate. Primary end point was the change in 6-minute walking distance (6MWD) from baseline, expressed as z-score. Secondary outcome was a change in Hb z-score from baseline.. We randomized 64 patients (33 IV iron and 31 oral iron) and followed them for 6 months. One month after the start of iron therapy, the 6MWD z-score of patients in the IV group had increased by 0.71 compared with -0.11 in the oral group (P = .01). At 3- and 6-month follow-ups, no significant differences in 6MWD z-scores were observed. Hb z-scores gradually increased in both groups and the rate of increase was not different between groups at 1, 3, and 6 months after initiation of iron therapy (overall P = .97).. In this trial involving anemic children with IBD, a single dose of IV ferric carboxymaltose was superior to oral ferrous fumarate with respect to quick improvement of physical fitness. At 3 and 6 months after initiation of therapy, no differences were discovered between oral and IV therapies. The increase of Hb over time was comparable in both treatment groups.. NTR4487 [Netherlands Trial Registry].

Topics: Administration, Oral; Anemia; Anemia, Iron-Deficiency; Child; Ferric Compounds; Hemoglobins; Humans; Inflammatory Bowel Diseases; Iron; Maltose; Treatment Outcome

Iron-deficiency anemia is common in inflammatory bowel disease, requiring oral or intravenous iron replacement therapy. Treatment with standard oral irons is limited by poor absorption and gastrointestinal toxicity. Ferric maltol is an oral iron designed for improved absorption and tolerability.. In this open-label, phase 3b trial (EudraCT 2015-002496-26 and NCT02680756), adults with nonseverely active inflammatory bowel disease and iron-deficiency anemia (hemoglobin, 8.0-11.0/12.0 g/dL [women/men]; ferritin, <30 ng/mL/<100 ng/mL with transferrin saturation <20%) were randomized to oral ferric maltol 30 mg twice daily or intravenous ferric carboxymaltose given according to each center's standard practice. The primary endpoint was a hemoglobin responder rate (≥2 g/dL increase or normalization) at week 12, with a 20% noninferiority limit in the intent-to-treat and per-protocol populations.. For the intent-to-treat (ferric maltol, n = 125/ferric carboxymaltose, n = 125) and per-protocol (n = 78/88) analyses, week 12 responder rates were 67% and 68%, respectively, for ferric maltol vs 84% and 85%, respectively, for ferric carboxymaltose. As the confidence intervals crossed the noninferiority margin, the primary endpoint was not met. Mean hemoglobin increases at weeks 12, 24, and 52 were 2.5 vs 3.0 g/dL, 2.9 vs 2.8 g/dL, and 2.7 vs 2.8 g/dL with ferric maltol vs ferric carboxymaltose. Treatment-emergent adverse events occurred in 59% and 36% of patients, respectively, and resulted in treatment discontinuation in 10% and 3% of patients, respectively.. Ferric maltol achieved clinically relevant increases in hemoglobin but did not show noninferiority vs ferric carboxymaltose at week 12. Both treatments had comparable long-term effectiveness for hemoglobin and ferritin over 52 weeks and were well tolerated.

Topics: Administration, Intravenous; Administration, Oral; Adult; Anemia, Iron-Deficiency; Female; Ferric Compounds; Hemoglobins; Humans; Inflammatory Bowel Diseases; Male; Maltose; Pyrones; Treatment Outcome

Secondary thrombocytosis is a common clinical feature. In patients with cancer, it is a risk factor for venous thromboembolic events. In inflammatory bowel disease (IBD), thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population. Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis. Here, we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis.. We performed a randomized, single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose (FCM) in patients with IBD with secondary thrombocytosis (platelets > 450 G/L). Changes in platelet counts, hemoglobin, iron parameters, disease activity, megakaryopoietic growth factors, erythropoietin, and platelet activity were assessed. Patients received placebo or up to 1500 mg iron as FCM. Endpoints were evaluated at week 6.. A total of 26 patients were included in the study, 15 patients were available for the per protocol analysis. A drop in platelets >25% (primary endpoint) was observed in 4 of 8 (50%, iron group) and 1 of 7 patients (14%, placebo group, P = 0.143). Mean platelet counts dropped on FCM but not on placebo (536 G/L to 411 G/L versus 580 G/L to 559 G/L; P = 0.002). Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM. The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression.. FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferric Compounds; Hepcidins; Humans; Inflammatory Bowel Diseases; Intercellular Signaling Peptides and Proteins; Male; Maltose; Middle Aged; P-Selectin; Platelet Activation; Platelet Aggregation; Platelet Count; Prognosis; Prospective Studies; Thrombocytosis; Young Adult

Iron-deficiency anemia is the most common systemic complication of inflammatory bowel diseases (IBD). Iron-deficiency anemia recurs frequently and rapidly after iron-replacement therapy in patients with IBD. We performed a randomized, placebo-controlled trial to determine if administration of ferric carboxymaltose (FCM) prevents anemia in patients with IBD and low levels of serum ferritin.. We performed a single-blind, multicenter study of nonanemic patients who had completed the FERGIcor study. Serum levels of ferritin were assessed every second month, and patients were given FCM (total iron dose, 1181 ± 662 mg; n = 105) or placebo (n = 99) when levels decreased to less than 100 μg/L. The primary end point was time to recurrence of anemia within 8 months. Secondary end points included changes of quality of life, disease activity, results from laboratory tests, and adverse events.. Anemia recurred in 26.7% of subjects given FCM and in 39.4% given placebo. The time to anemia recurrence was longer in the FCM group (hazard ratio, 0.62; 95% confidence interval, 0.38-1.00; P = .049). Markers of body levels of iron increased or remained at normal levels in subjects given FCM (ferritin increased by 30.3 μg/L, transferrin saturation increased by 0.6%) but decreased in the group given placebo (ferritin decreased by 36.1 μg/L, transferrin saturation decreased by 4.0%). Changes in quality of life and disease activity were comparable between groups. Adverse events were reported in 59.0% of the FCM group and 50.5% of the placebo group, and serious adverse events were reported in 6.7% and 8.1%, respectively.. FCM prevents recurrence of anemia in patients with IBD, compared with placebo. Nevertheless, the high rate of anemia recurrence warrants optimization of the frequency and requirements for FCM treatment.

Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Dietary Supplements; Female; Ferric Compounds; Humans; Inflammatory Bowel Diseases; Male; Maltose; Middle Aged; Placebos; Secondary Prevention; Single-Blind Method; Treatment Outcome; Young Adult

Iron deficiency anemia (IDA) is common in chronic diseases and intravenous iron is an effective and recommended treatment. However, dose calculations and inconvenient administration may affect compliance and efficacy. We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen (FCM) with individually calculated iron sucrose (IS) doses in patients with inflammatory bowel disease (IBD) and IDA.. This randomized, controlled, open-label, multicenter study included 485 patients with IDA (ferritin <100 μg/L, hemoglobin [Hb] 7-12 g/dL [female] or 7-13 g/dL [male]) and mild-to-moderate or quiescent IBD at 88 hospitals and clinics in 14 countries. Patients received either FCM in a maximum of 3 infusions of 1000 or 500 mg iron, or Ganzoni-calculated IS dosages in up to 11 infusions of 200 mg iron. Primary end point was Hb response (Hb increase ≥ 2 g/dL); secondary end points included anemia resolution and iron status normalization by week 12.. The results of 240 FCM-treated and 235 IS-treated patients were analyzed. More patients with FCM than IS achieved Hb response (150 [65.8%] vs 118 [53.6%]; 12.2% difference, P = .004) or Hb normalization (166 [72.8%] vs 136 [61.8%]; 11.0% difference, P = .015). Both treatments improved quality of life scores by week 12. Study drugs were well tolerated and drug-related adverse events were in line with drug-specific clinical experience. Deviations from scheduled total iron dosages were more frequent in the IS group.. The simpler FCM-based dosing regimen showed better efficacy and compliance, as well as a good safety profile, compared with the Ganzoni-calculated IS dose regimen.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Comorbidity; Dose-Response Relationship, Drug; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hemoglobins; Humans; Inflammatory Bowel Diseases; Infusions, Intravenous; Male; Maltose; Middle Aged; Outcome Assessment, Health Care; Treatment Outcome; Young Adult

Iron deficiency and iron deficiency anemia are common in pediatric inflammatory bowel disease and often require supplementation with iron. There is a paucity of literature regarding optimal iron formulation. The aim of this study is to compare outcomes in pediatric patients with inflammatory bowel disease receiving either iron sucrose or ferric carboxymaltose during inpatient hospitalizations.. This was a single-center retrospective study of pediatric patients with inflammatory bowel disease admitted for newly diagnosed disease or flare who received either iron sucrose or ferric carboxymaltose. Linear regression was used to assess differences in iron repletion. Longitudinal linear mixed-effects models and generalized estimating equations compared hematologic and iron outcomes 6 months post-iron repletion.. Thirty patients received ferric carboxymaltose. Sixty-nine patients received iron sucrose. Baseline hemoglobin and iron deficits were similar in both groups. A larger percentage of iron deficit was repleted in the ferric carboxymaltose group (81.4%) compared with iron sucrose (25.9%) (P < 0.001) with fewer infusions. Cumulative doses of ferric carboxymaltose administered (18.7 mg/kg) were higher than iron sucrose (6.1 mg/kg) (P < 0.001). Hemoglobin increased more quickly with ferric carboxymaltose compared with iron sucrose (P = 0.04 and P = 0.02, respectively). Total iron binding capacity and red cell distribution width levels decreased more over time with ferric carboxymaltose vs iron sucrose (P < 0.01 and P = 0.01, respectively). No adverse effects were seen.. Hematologic and iron parameters responded more quickly with fewer infusions in patients who received ferric carboxymaltose vs iron sucrose. Patients who received ferric carboxymaltose achieved a higher percentage of iron deficit repleted.

Topics: Child; Ferric Compounds; Ferric Oxide, Saccharated; Hemoglobins; Humans; Inflammatory Bowel Diseases; Iron; Retrospective Studies

We evaluated an on-demand ferric carboxymaltose (FCM) infusion strategy in inflammatory bowel disease (IBD) patients with iron deficiency anemia (IDA).. The primary outcome was the response rate to single or multiple FCM infusions after 12 months. Secondary outcomes were the response rate to a single FCM infusion after 3 months and the FCM safety profile.. We retrospectively included 185 IBD patients who received at least one FCM infusion of 500 mg, between 2015 and 2018. FCM was administered to patients with Hb ≤10 g/dL and hypoferritinemia and repeated according to the physician's assessment. Complete response (CR) was defined as Hb ≥12 g/dL (≥13 g/dL for men) or Hb increase ≥2 g/dL. Partial response (PR) was defined as an Hb increase between 1 and 2 g/dL. A univariate analysis was performed at 3 and 12 months.. After 12 months, the response rate was 75.1% (CR, 48.6%; PR, 26.4%; mean number of FCM infusions, 1.7 ± 1.1). In total 169/185 patients received a single FCM infusion during the first 3 months and 79.2% achieved response (CR, 56.8%; PR, 22.4%). At univariate analysis, no variable was associated with response. No adverse events were reported.. An on-demand strategy was effective and well-tolerated in treating IDA in IBD patients.

Topics: Anemia, Iron-Deficiency; Chronic Disease; Ferric Compounds; Humans; Inflammatory Bowel Diseases; Male; Maltose; Retrospective Studies; Treatment Outcome

Chronic non-specific multiple ulcers of the small intestine is a disease condition postulated in Japan. It is an uncommon gastrointestinal disease that causes chronic anemia and hypoalbuminemia by causing numerous ulcers without any histopathologically identifiable features. In recent years, it has been revealed that the mutations of SLCO2A1, which codes the prostaglandin transporter protein, are the cause of this disease;it is called the new name "chronic enteropathy associated with SLCO2A1 gene." The ileum, except the terminal ileum, is the most common place making it difficult to identify major lesions. Other than conservative treatments, such as nutrition therapy and iron supplements, no effective treatment has been identified so far. We present a case of chronic non-specific multiple ulcers of the small intestine diagnosed by capsule endoscopy and effectively treated by ferric carboxymaltose. A 48-year-old female had chronic iron deficiency anemia since around the age of 15. Because of severe anemia, the patient had upper and lower endoscopy at the age of 47 to find the source of the bleeding, but it was not detected. Except for the terminal ileum, the capsule endoscopy revealed ring-like ulcers, tape-like ulcers, and oblique ulcer scars in the ileum. Genetic analysis showed a homozygous mutation in intron 7, c.940+1G>A, indicating a definitive diagnosis of non-specific multiple ulcers of the small intestine. Anemia and anemia-related symptoms such as general malaise persisted despite continuous oral administration of iron drugs. Three intravenous injections of ferric carboxymaltose increased hemoglobin and enhanced the symptoms.

Topics: Anemia; Anemia, Iron-Deficiency; Capsule Endoscopy; Female; Ferric Compounds; Humans; Inflammatory Bowel Diseases; Iron; Maltose; Middle Aged; Organic Anion Transporters; Ulcer

Although intravenous ferric carboxymaltose (FCM) is effective in treating iron deficiency anemia (IDA) in paediatric inflammatory bowel disease (pIBD), no data are available on its post-infusion related risks.. We assessed the efficacy of FCM and the rate of post-infusion hypophosphatemia in a large cohort of children with IBD and IDA.. All children with IBD with IDA treated with FCM over 5-year period were reviewed. Disease activity, biohumoral assessment and treatments were evaluated at baseline, 4-6 and 12 weeks after each infusion.. 128 patients [median age at first infusion: 13 years] were identified, 81 (63.3%) were <14 years, 10 (7.8%) <6 years. Eighty-three children (64.8%) received one infusion, whilst 45 (35.2%) repeated infusions. A significant increase in Hb (p<0.001), iron (p<0.001) and ferritin (p<0.001) was observed 4-6 and 12 weeks post-infusion. Hb gain was unrelated to disease severity. Low baseline iron was the main predicting factor for repeated infusions (p<0.05). Three patients reported infusion reactions, none <6 years. Twenty-five children had low post-infusion serum phosphate (11 were <14 years, 3 <6 years). Two children developed severe hypophosphatemia.. FCM administration is effective for IDA management in pIBD, including children <6 years. Due to the high prevalence of post-infusion hypophosphatemia, serum phosphate monitoring should be mandatory.

Topics: Administration, Intravenous; Adolescent; Anemia, Iron-Deficiency; Child; Child, Preschool; Female; Ferric Compounds; Ferritins; Hemoglobins; Humans; Hypophosphatemia; Inflammatory Bowel Diseases; Iron; Male; Maltose; Phosphates; Prevalence; Risk Factors; Severity of Illness Index; Treatment Outcome

Topics: Disaccharides; Ferric Compounds; Humans; Hypophosphatemia; Incidence; Inflammatory Bowel Diseases; Iron; Maltose

Topics: Disaccharides; Ferric Compounds; Humans; Hypophosphatemia; Incidence; Inflammatory Bowel Diseases; Iron; Maltose

Topics: Anemia, Iron-Deficiency; Cost-Benefit Analysis; Denmark; Disaccharides; Ferric Compounds; Humans; Inflammatory Bowel Diseases; Maltose

Topics: Anemia, Iron-Deficiency; Cost-Benefit Analysis; Denmark; Disaccharides; Ferric Compounds; Humans; Inflammatory Bowel Diseases; Maltose

Iron deficiency and iron deficiency anaemia are common complications in inflammatory bowel disease (IBD). In patients with moderate-to-severe anaemia, oral iron intolerance or ineffectiveness of oral iron, ferric carboxymaltose and iron isomaltoside are widely used. Hypophosphatemia is a side effect of both preparations.. To investigate the occurrence of hypophosphatemia in IBD patients with iron deficiency/iron deficiency anaemia treated with high-dose intravenous iron.. A prospective observational study of adult IBD patients with iron deficiency/iron deficiency anaemia was conducted at two study sites where patients received 1000 mg of ferric carboxymaltose or iron isomaltoside. At baseline, weeks 2 and 6, blood and faecal samples were collected. The primary endpoint was to determine the incidence of moderate-to-severe hypophosphatemia. Secondary endpoints included the total incidence of hypophosphatemia, possible risk factors for hypophosphatemia, and response to single-dose intravenous iron.. One hundred and thirty patients were included. In the per-protocol set, 52 patients received ferric carboxymaltose and 54 patients received iron isomaltoside. Ferric carboxymaltose treatment had a significantly higher incidence of moderate-to-severe hypophosphatemia compared with iron isomaltoside at week 2 (56.9% vs 5.7%, P < 0.001) and a higher incidence at week 6 (13.7% vs 1.9%, P = 0.054).The overall incidence of hypophosphatemia was significantly higher with ferric carboxymaltose compared with iron isomaltoside treatment at weeks 2 (72.5% vs 11.3%, P < 0.001) and 6 (21.6% vs 3.7%, P = 0.013).. In IBD patients with iron deficiency/iron deficiency anaemia, ferric carboxymaltose was associated with higher incidence, severity and persistence of hypophosphatemia compared with iron isomaltoside. The presence of moderate-to-severe hypophosphatemia beyond 6 weeks is a clinical concern that requires further investigation.

Topics: Administration, Intravenous; Adult; Anemia, Iron-Deficiency; Disaccharides; Female; Ferric Compounds; Humans; Hypophosphatemia; Incidence; Inflammatory Bowel Diseases; Male; Maltose; Middle Aged; Norway; Prospective Studies; Quality of Life; Risk Factors

The main objective of our study was to determinate the effectiveness of intravenous iron treatment with ferric carboxymaltose in inflammatory bowel disease (IBD) patients. Our other objectives were to study parameters that would predict a good response to the treatment and to chart out possible side-effects of the treatment.. In our retrospective chart review study we collected clinical data and laboratory results related to IBD from medical records of 87 IBD patients who were treated with ferric carboxymaltose in Helsinki University Hospital between 2014 and 2016.. The mean increase in hemoglobin levels of the patients was 24.6 g/l (+ 24%) after one month, 27.6 g/l (+ 27%) after three months and 26.0 g/l (+ 27%) after six months. Nine out of 87 treated patients (10.3%) reported side-effects during the iron infusion. A linear regression model assessing the change in hemoglobin levels after six months demonstrated close correlation with transferrin receptor count (p = .004) and ferritin (p = .016) with an adjusted R square of 0.463.. Ferric carboxymaltose was found to be an effective and well tolerated treatment for iron deficiency anemia in patients with IBD. The results of our study further strengthen the current knowledge of the effectiveness and safety of the treatment.

Topics: Administration, Intravenous; Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Exanthema; Female; Ferric Compounds; Ferritins; Finland; Humans; Inflammatory Bowel Diseases; Iron; Linear Models; Male; Maltose; Middle Aged; Nausea; Receptors, Transferrin; Retrospective Studies; Treatment Outcome; Young Adult

The incidence of inflammatory bowel disease (IBD) in Denmark is among the highest in the world, with Crohn's disease and ulcerative colitis occurring at rates of 9.1 and 18.6 per 100,000 person-years respectively in 2010-2013. Anemia is the most prevalent extraintestinal complication of IBD, most commonly caused by iron deficiency. In treating IBD-associated iron deficiency anemia (IDA), intravenous iron is more effective and better tolerated and shows a faster response than oral iron. The present study evaluated resource use and costs associated with using iron isomaltoside (Monofer; IIM) versus ferric carboxymaltose (Ferinject; FCM) in patients with IDA and IBD in Denmark.. A budget impact model was developed to evaluate the cost of IIM compared with FCM from a Danish healthcare payer perspective. Iron deficits were modeled using dosing tables and a joint distribution of bodyweight [mean 75.4 kg, standard deviation (SD) 17.4 kg] and hemoglobin (mean 10.8 g/dL, SD 1.4 g/dl) based on observational data from patients with IBD. Retreatment frequency was modeled using a pooled retrospective analysis of randomized trial data, and costs were modeled using diagnosis-related groups with an outpatient infusion cost of DKK 2855.. Using IIM required 1.2 infusions (per treatment) to correct the mean iron deficit compared with 1.6 with FCM. Treating 2.54 patients with IIM would therefore avoid one infusion compared with FCM. Patients using IIM required multiple infusions in 25.0% of cases compared with 64.3% with FCM. Over 5 years, total estimated costs were DKK 21,406 per patient with IIM compared with DKK 28,137 with FCM, corresponding to savings of DKK 6731 with IIM.. Using IIM in place of FCM markedly reduced the number of iron infusions required in patients with IBD and IDA in Denmark. The reduction in infusions was accompanied by reductions in cost compared with FCM.. Pharmacosmos A/S.

Topics: Administration, Intravenous; Adult; Anemia, Iron-Deficiency; Cost-Benefit Analysis; Denmark; Disaccharides; Female; Ferric Compounds; Hemoglobins; Humans; Inflammatory Bowel Diseases; Maltose; Middle Aged; Retrospective Studies

Iron deficiency anaemia (IDA) is the main extraintestinal manifestation affecting patients with inflammatory bowel disease (IBD). The Health Technology Assessment approach was applied to evaluate the sustainability of intravenous (IV) iron formulations in the Italian hospital setting, with particular focus on ferric carboxymaltose. Data on the epidemiology of IBD and associated IDA, in addition to the efficacy and safety of IV iron formulations currently used in Italy, were retrieved from scientific literature. A hospital-based cost-analysis of the outpatient delivery of IV iron treatments was performed. Organizational and ethical implications were discussed. IDA prevalence in IBD patients varies markedly from 9 to 73%. IV iron preparations were proven to have good efficacy and safety profiles, and ferric carboxymaltose provided a fast correction of haemoglobin and serum ferritin levels in iron-deficient patients. Despite a higher price, ferric carboxymaltose would confer a beneficial effect to the hospital, in terms of reduced cost related to individual patient management and additionally to the patient by reducing the number of infusions and admissions to healthcare facilities. Ethically, the evaluation is appropriate due to its efficacy and compliance. This assessment supports the introduction of ferric carboxymaltose in the Italian outpatient setting.

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Ferric Compounds; Hemoglobins; Hospitals; Humans; Inflammatory Bowel Diseases; Infusions, Intravenous; Iron; Italy; Maltose; Technology Assessment, Biomedical; Treatment Outcome

Anemia represents one of the most common and often the least treated complications of inflammatory bowel disease (IBD).. Our study investigates experiences and preferences concerning anemia treatment in patients with IBD.. IBD patients previously diagnosed with anemia were invited to participate in an anonymous survey between July and September 2015, which assessed demographic and clinical data, and experiences regarding anemia treatment.. A total of 118 IBD patients were invited to participate in the study, of which 100 (85%) were included in the analysis. Seventy-five percent of patients reported a high personal burden related to intravenous therapy, while the majority of companions (76%) declared a moderate burden. The increased importance assigned to the possibility of a single session treatment was significantly associated with age (Beta=0.01; p=0.03), working status (Beta=0.02; p=0.04), anemia severity (severe vs. mild, Beta=0.42; p=0.03), and intravenous treatment (Beta=0.44; p=0.001).. Most patients reported a high personal and a moderate companions' burden. Having the possibility of effective single dose intravenous therapy was of great importance. Patients' perspective provides key information for evaluating the indirect costs of anemia treatment in IBD which, according to the health technology assessment approach, could be useful in a patient centered decision making process.

Topics: Absenteeism; Administration, Intravenous; Administration, Oral; Adult; Anemia; Caregivers; Cost of Illness; Cross-Sectional Studies; Employment; Female; Ferric Compounds; Health Care Surveys; Hemoglobins; Humans; Inflammatory Bowel Diseases; Iron; Male; Maltose; Middle Aged; Patient Preference; Severity of Illness Index

Iron deficiency is the leading cause of anemia in patients with inflammatory bowel disease (IBD). Intravenous iron is the first-line treatment for clinically active IBD or previous oral iron intolerance. The aim of the present study was to develop a comparative model of iron deficiency and delivery for iron isomaltoside (IIM), ferric carboxymaltose (FCM), low molecular weight iron dextran (LMWID), and iron sucrose (IS) in the treatment of iron deficiency anemia associated with IBD. Areas covered: A model was developed to evaluate iron delivery characteristics, resource use and costs associated with IIM, FCM, LMWID and IS. Iron deficiency was modeled using dosing tables and retreatments were modeled based on a pooled retrospective analysis. The analyses were conducted over 5 years in patients with IBD with mean bodyweight of 75.4 kg and hemoglobin levels of 10.77 g/dL based on observational data. Expert opinion: The modeling analysis showed that using IIM required 1.2 infusions (per treatment) to correct the mean iron deficit, compared with 1.6, 1.2, and 7.1 with FCM, LMWID and IS, respectively. Costs were estimated to be 2,518 pounds sterling (GBP) per patient with IIM or LMWID, relative to GBP 3,309 with FCM or GBP 14,382 with IS.

Topics: Anemia, Iron-Deficiency; Budgets; Disaccharides; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Inflammatory Bowel Diseases; Infusions, Intravenous; Iron-Dextran Complex; Maltose; Retrospective Studies; United Kingdom

Anaemia and iron deficiency are very common in inflammatory bowel disease. Clinical trials have shown intravenous iron to be effective and well tolerated. However, published experience in clinical practice with specific evaluation of the effect on quality of life is limited.. We carried out a prospective, multicentre, observational study on the effects of ferric carboxymaltose in the treatment of iron deficiency anaemia in inflammatory bowel disease. Anaemia and iron deficiency were defined according to World Health Organization criteria. Efficacy and safety were evaluated at infusion, at 2 weeks and at 12 weeks. Quality of life was evaluated according to the SIBDQ-9 index. Complete response was defined as anaemia correction or more tan 2 g/dL increase in haemoglobin.. A total of 88 courses of ferric carboxymaltose in 72 patients were evaluated. Complete response was observed in 46% of patients at week 2, and 81.2% at week 12. Quality of life improved significatively at week 2 in both complete responders and partial responders (p<0.0005); complete responders showed siginficantly better response (p=0.016). No predictive factor was identified. Only one transient adverse effect was observed; however, this was severe.. Ferric carboxymaltose showed comparable efficacy to that demonstrated in clinical trials. After only two weeks of treatment, there was a significant improvement in quality of life, with a greater effect observed in those patients with a complete haematologic response. Intravenous iron can very quickly improve quality of life in inflammatory bowel disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Female; Ferric Compounds; Humans; Inflammatory Bowel Diseases; Male; Maltose; Middle Aged; Prospective Studies; Quality of Life; Young Adult

Topics: Antibodies, Monoclonal, Humanized; Ferric Compounds; Health Facilities; Humans; Inflammatory Bowel Diseases; Infliximab; Infusions, Intravenous; Maltose; Patient Compliance; Patient Education as Topic

Topics: Administration, Oral; Anemia, Iron-Deficiency; Cholecalciferol; Ferric Compounds; Humans; Inflammatory Bowel Diseases; Infusions, Intravenous; Injections, Intramuscular; Maltose; Vitamin D Deficiency

To obtain preliminary safety and efficacy data on intravenous (IV) administration of infliximab (IFX) and ferric carboxymaltose (FCM) to inflammatory bowel disease (IBD) patients in a single treatment session.. A two-phase non-interventional, observational, prospective pilot study was performed to evaluate safety and efficacy of FCM given immediately after IFX. IBD patients were recruited consecutively in the outpatient clinic in two groups. Control group patients (n = 12) received FCM on a separate day from IFX. Subsequently, single-session group patients (n = 33) received FCM after IFX on the same day. All patients received 5mg/kg IFX and 1000mg FCM for iron-restricted anemia (IRA) or 500mg FCM for iron deficiency without anemia. Safety assessment was performed by recording adverse events (AEs) during and immediately after infusion, 30 minutes afterwards, and via follow-up at 7 days and 8 weeks. For efficacy assessment, hematological parameters were assessed prior to FCM infusion (pre-FCM) and after 8 weeks. Economic impact of FCM given immediately after IFX was assessed.. All 45 patients (35 Crohn´s disease, 10 ulcerative colitis) received IFX 5mg/kg. 21 patients received 500mg FCM and 24 received 1000mg. FCM administration immediately after IFX corrected iron deficiency or IRA as shown by increases in hematological parameters. No AEs were reported during the safety evaluation at the end of FCM or IFX administration, 30 minutes, 7 days and 8 weeks afterwards, in either control or single-session groups. Total cost per patient for single-session administration was 354.63€; for patients receiving IFX and FCM on separate days, it was 531.94€, giving a 177.31€ per-patient cost saving.. Single-session administration of FCM after IFX was safe and effective in IBD patients and can offer a good cost-benefit ratio and improve treatment adherence. To our knowledge, this study is the first to evaluate FCM and IFX administration in a single treatment session.

Topics: Adult; Anemia, Iron-Deficiency; Cost-Benefit Analysis; Drug Administration Schedule; Ferric Compounds; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Infliximab; Infusions, Intravenous; Male; Maltose; Middle Aged; Patient Compliance; Pilot Projects; Prospective Studies; Treatment Outcome

The treatment of iron deficiency anemia in children with inflammatory bowel disease is a particular challenge and often insufficient. Absorption of orally given iron may be impaired by intestinal inflammation and treatment with oral iron may aggravate intestinal inflammation. This retrospective study is the first to describe the use of intravenous ferric carboxymaltose (FCM) in the pediatric setting.. All subjects who had received at least one dose of FCM intravenously in the observation period were included in this analysis with data collected for up to 3 months post last FCM dose.. In total, 72 children between 0 and 18 years with underlying gastrointestinal disorders had been treated for concomitant iron deficiency anemia. The majority of patients had Crohn's disease (40.3%) or ulcerative colitis (30.5%). The total number of FCM administrations was 147, the mean number per patient was 2.0 and the mean cumulative dose 821 mg iron (median single dose: 500 mg; max. 1000 mg). Post administration of FCM, correction of iron deficiency anemia was observed with improved mean hemoglobin levels from 9.5 g/dL at baseline to 11.9 g/dL within 5-12 weeks. Decreases in white cell count, platelets and C-reactive protein were observed post FCM, potentially suggesting reduced inflammation with iron repletion. Three subjects reported mild adverse drug reactions related to FCM; two of these were considered to be potentially related to long duration of administration and to high volume of saline solution for dilution. As such, the method of administration was amended to have a maximum infusion time of 60 minutes and dilution with less than or equal to 100 mL saline solution.. Overall FCM was well tolerated in this pediatric population and appeared to be effective in correcting iron deficiency anemia. We cannot exclude that the correction of iron deficiency anaemia is in some part due to the treatment of the underlying disease and not related to the iron supplementation only.

Topics: Adolescent; Anemia, Iron-Deficiency; Child; Child, Preschool; Female; Ferric Compounds; Gastrointestinal Diseases; Humans; Infant; Infant, Newborn; Inflammatory Bowel Diseases; Infusions, Intravenous; Male; Maltose; Retrospective Studies; Treatment Outcome

We analyzed iron deficiency and the therapeutic response following intravenous ferric carboxymaltose in a large single-center inflammatory bowel disease (IBD) cohort.. 250 IBD patients were retrospectively analyzed for iron deficiency and iron deficiency anemia. A subgroup was analyzed regarding efficacy and side effects of iron supplementation with ferric carboxymaltose.. In the cohort (n = 250), 54.4% of the patients had serum iron levels ≤60 μg/dl, 81.2% had ferritin ≤100 ng/ml, and 25.6% had hemoglobin (Hb) of ≤12 g/dl (females) or ≤13 g/dl (males). In the treatment subcohort (n = 80), 83.1% of the patients had iron ≤60 μg/dl, 90.4% had ferritin ≤100 ng/ml, and 66.7% had Hb ≤12/13 g/dl before ferric carboxymaltose treatment. After a median dose of 500 mg ferric carboxymaltose, 74.7% of the patients reached iron >60 μg/dl, 61.6% had ferritin >100 ng/ml, and 90.7% reached Hb >12/13 g/dl at follow-up (p < 0.0001 for all parameters vs. pretreatment values). The most frequent adverse event was a transient increase of liver enzymes with male gender as risk factor (p = 0.008, OR 8.62, 95% CI 1.74-41.66).. Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients.

Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Cohort Studies; Female; Ferric Compounds; Ferritins; Hemoglobins; Humans; Inflammatory Bowel Diseases; Infusions, Intravenous; Iron; Male; Maltose; Middle Aged; Treatment Outcome; Young Adult

Topics: Anemia, Iron-Deficiency; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Inflammatory Bowel Diseases; Injections, Intravenous; Maltose; Quality of Life; Treatment Outcome

Ferric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD). In most trials, patients received either FCM doses of < or = 1000 mg, administered intravenously (i.v.) over < or = 15 min. or oral ferrous sulfate (FeSulf) 325 mg (65 mg iron), three times daily (t.i.d.), or 304 mg (100 mg iron), twice daily (b.i.d.). In one trial, patients on HD received 200 mg i.v. of either FCM or iron sucrose (ISC), two-to-three times weekly. In a pilot study in patients with CHF and CKD, patients received 200 mg of FCM by push injection compared with 200 mg of ISC slow injection. FCM was usually administered until the patient's calculated total iron replacement dose was achieved. Treatment with FCM improved indices of anemia (hemoglobin [Hb], ferritin and transferrin saturation [TSAT] values). In patients on HD with IDA secondary to CKD, FCM demonstrated comparable efficacy to ISC in achieving an increase in Hb. In patients with IBD or PPA, improvements in Hb levels were more rapid with FCM than with FeSulf. Patients with PPA receiving FCM compared with those receiving oral iron achieved an Hb rise > or = 2.0 g/dl earlier (7 days compared with 14 days; p < 0.001), were more likely to achieve an Hb rise > or = 3.0 g/dl at any time beginning at day 14 (86.3% compared with 60.4%; p < 0.001), and achieve an Hb > 12.0 g/dl at the end of the study (Day 42; 90.5% compared with 68.6%, p < 0.01). Serum ferritin increased in the i.v. FCM treatment group, but not in the oral iron group. Differences between groups were significant at each study interval. TSAT increased significantly at every interval in both groups; however, FCM-treated patients showed higher TSAT at each interval after the first week. FCM improved patient quality of life to an equivalent extent to oral FeSulf in patients with IBD or PPA, and to a greater extent than oral FeSulf in women with AUB. FCM also improved quality of life as well as functional symptoms and exercise capacity in patients with CHF. Safety data from more than 3000 patients showed that FCM was well tolerated. No safety concerns have been identified in breas

Topics: Anemia; Anemia, Iron-Deficiency; Breast Feeding; Female; Ferric Compounds; Ferritins; Heart Failure; Humans; Infant; Inflammatory Bowel Diseases; Maltose; Pilot Projects; Puerperal Disorders; Randomized Controlled Trials as Topic; Renal Insufficiency; Safety; Transferrin

Anemia is common in IBD patients and intravenous iron treatment is preferred. The drug cost of intravenous iron carboxymaltose is approximately twice the cost of intravenous iron sucrose. The aim was to evaluate the health care costs of intravenous iron sucrose (Venofer®, Vifor) and intravenous iron carboxymaltose (Ferinject®, Vifor) treatment to IBD patients in an outpatient setting.. Based on data from 111 IBD patients treated with intravenous iron in an outpatient setting health care costs were evaluated by means of Budget Impact Analysis, Cost Effective Analysis and Cost Benefit Analysis.. The Cost Effective Analysis showed that iron carboxymaltose was more cost-effective than iron sucrose, due to fewer outpatient setting visits. Even a sensitivity analysis using a reduced patient income (50%) in the Cost Effective Analysis showed iron carboxymaltose to be the most cost effective treatment. The Budget Impact Analysis from a hospital perspective showed that iron carboxymaltose was more expensive than iron sucrose regardless of the dose given. In contrast the Cost Benefit Analysis showed that the average patients' 'willingness to pay' for a total of iron dose of 1400 mg was €233 in order to reduce the number of infusions from 7 to 2 by using iron carboxymaltose rather than iron sucrose.. Both the Cost Effective Analysis and the Cost Benefit Analysis showed clearly that iron carboxymaltose is a more cost effective way of giving intravenous iron than iron sucrose in IBD patients. Only the Budget Impact Analysis showed that intravenous iron sucrose was the cheapest choice if only direct cost was included in the analysis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ambulatory Care; Anemia, Iron-Deficiency; Cost-Benefit Analysis; Drug Costs; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Health Care Costs; Humans; Inflammatory Bowel Diseases; Infusions, Intravenous; Male; Maltose; Middle Aged; Young Adult