losartan-potassium and Crohn-Disease

Inflammatory bowel disease affects approximately seven million people globally. Iron deficiency anaemia can occur as a common systemic manifestation, with a prevalence of up to 90%, which can significantly affect quality of life, both during periods of active disease or in remission. It is important that iron deficiency anaemia is treated effectively and not be assumed to be a normal finding of inflammatory bowel disease. The various routes of iron administration, doses and preparations present varying advantages and disadvantages, and a significant proportion of people experience adverse effects with current therapies. Currently, no consensus has been reached amongst physicians as to which treatment path is most beneficial.. The primary objective was to evaluate the efficacy and safety of the interventions for the treatment of iron deficiency anaemia in people with inflammatory bowel disease.. We searched CENTRAL, MEDLINE, Embase, and two other databases on 21st November 2019. We also contacted experts in the field and searched references of trials for any additional trials.. Randomised controlled trials investigating the effectiveness and safety of iron administration interventions compared to other iron administration interventions or placebo in the treatment of iron deficiency anaemia in inflammatory bowel disease. We considered both adults and children, with studies reporting outcomes of clinical, endoscopic, histologic or surgical remission as defined by study authors.. Two review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology.. We included 11 studies (1670 randomised participants) that met the inclusion criteria. The studies compared intravenous iron sucrose vs oral iron sulphate (2 studies); oral iron sulphate vs oral iron hydroxide polymaltose complex (1 study); oral iron fumarate vs intravenous iron sucrose (1 study); intravenous ferric carboxymaltose vs intravenous iron sucrose (1 study); erythropoietin injection + intravenous iron sucrose vs intravenous iron sucrose + injection placebo (1 study); oral ferric maltol vs oral placebo (1 study); oral ferric maltol vs intravenous ferric carboxymaltose (1 study); intravenous ferric carboxymaltose vs oral iron sulphate (1 study); intravenous iron isomaltoside vs oral iron sulphate (1 study); erythropoietin injection vs oral placebo (1 study). All studies compared participants with CD and UC together, as well as considering a range of disease activity states. The primary outcome of number of responders, when defined, was stated to be an increase in haemoglobin of 20 g/L in all but two studies in which an increase in 10g/L was used. In one study comparing intravenous ferric carboxymaltose and intravenous iron sucrose, moderate-certainty evidence was found that intravenous ferric carboxymaltose was probably superior to intravenous iron sucrose, although there were responders in both groups (150/244 versus 118/239, RR 1.25, 95% CI 1.06 to 1.46, number needed to treat for an additional beneficial outcome (NNTB) = 9). In one study comparing oral ferric maltol to placebo, there was low-certainty evidence of superiority of the iron (36/64 versus 0/64, RR 73.00, 95% CI 4.58 to 1164.36). There were no other direct comparisons that found any difference in the primary outcomes, although certainty was low and very low for all outcomes, due to imprecision from sparse data and risk of bias varying between moderate and high risk. The reporting of secondary outcomes was inconsistent. The most common was the occurrence of serious adverse events or those requiring withdrawal of therapy. In no comparisons was there a difference seen between any of the intervention agents being studied, although the certainty was very low for all comparisons made, due to risk of bias and significant imprecision due to the low numbers of events. Time to remission, histological and biochemical outcomes were sparsely reported in the studies. None of the other secondary outcomes were reported in any of the studies. An analysis of all intravenous iron preparations to all o. Intravenous ferric carboxymaltose probably leads to more people having resolution of IDA (iron deficiency anaemia) than intravenous iron sucrose. Oral ferric maltol may lead to more people having resolution of IDA than placebo. We are unable to draw conclusions on which of the other treatments is most effective in IDA with IBD (inflammatory bowel disease) due to low numbers of studies in each comparison area and clinical heterogeneity within the studies. Therefore, there are no other conclusions regarding the treatments that can be made and certainty of all findings are low or very low. Overall, intravenous iron delivery probably leads to greater response in patients compared with oral iron, with a NNTB (number needed to treat) of 11. Whilst no serious adverse events were specifically elicited with any of the treatments studied, the numbers of reported events were low and the certainty of these findings very low for all comparisons, so no conclusions can be drawn. There may be more withdrawals due to such events when oral is compared with intravenous iron delivery. Other outcomes were poorly reported and once again no conclusions can be made as to the impact of IDA on any of these outcomes. Given the widespread use of many of these treatments in practice and the only guideline that exists recommending the use of intravenous iron in favour of oral iron, research to investigate this key issue is clearly needed. Considering the current ongoing trials identified in this review, these are more focussed on the impact in specific patient groups (young people) or on other symptoms (such as fatigue). Therefore, there is a need for studies to be performed to fill this evidence gap.

Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Bias; Colitis, Ulcerative; Crohn Disease; Disaccharides; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Fumarates; Hematinics; Humans; Iron Compounds; Maltose; Middle Aged; Placebos; Pyrones; Randomized Controlled Trials as Topic; Young Adult

The development of a stepwise therapy, as detailed below, can be administered to the mostly young patients with Crohn's disease and ulcerative colitis on an out-patient basis and appropriate to their needs. This is true not only for the activity of the disease, but also for extraintestinal manifestations. The numerous variations in the stepwise anti-inflammatory therapy of chronic inflammatory bowel disease, but also in the substitution therapy of deficiency states and the therapy of accompanying extraintestinal diseases provide the gastroenterologist with the possibility of a long-term treatment tailored to the needs of the individual patient.

Topics: Anemia, Iron-Deficiency; Colitis, Ulcerative; Crohn Disease; Erythropoietin; Ferric Compounds; Ferrous Compounds; Humans; Recombinant Proteins

If one reviews the literature with zeal, it is increasingly apparent that few organs escape recruitment when IBD is chronic or progressive. Insights into mucosal pathophysiology have helped with understanding the more frequent extraintestinal manifestations, but the mechanisms attendant to the development of less common events (e.g. acute pancreatitis, concurrent gluten sensitive enteropathy, or active pulmonary disease) remain either poorly studied or obscure. It is particularly interesting, however, to read reports of abnormal pulmonary function, generally of the obstructive type, correlated to measurements of abnormal intestinal permeability in patients with either active pulmonary sarcoid or pulmonary involvement in Crohn's disease. It has been further speculated that similarities in the mucosal immune system of the lung and intestine are responsible for evidence of bronchial hyperreactivity in patients with active IBD. Finally, it is important to recognize that extensions of the inflammatory process are not restricted to the development of organ-based events but may be responsible for some of the most frequent systemic abnormalities detected in IBD patients. It is now also well confirmed that the cytokine environment in IBD can support activated coagulation and, in some clinical situations, overt vascular thrombosis. The cerebrovascular complications of IBD are well recognized and range from peripheral venous thrombosis to central stroke syndromes and pseudotumor cerebri. Reports of focal white matter lesions in the brains of patients with IBD or an increased incidence of polyneuropathy may be other clinical examples of regional microvascular clotting. Microvascular injury appears to be more ubiquitously present, with reports ranging from a speculated primary causative role (e.g., granulomatous vasculitis in the mesenteric circulation) to the utility of nailbed vasospasm, in Crohn's disease, as a clinical marker for disease activity. It is also reported that IL-6 suppression of erythropoietin production is a major feature of the chronic anemia seen in active IBD. Moreover, the capacity of peripheral monocytes from active IBD patients to secrete TNF and IL-8 is reported predictive for the degree of therapeutic response from recombinant erythropoietin. These collected observations constitute another excellent example of the symmetry between basic science and clinical utility. It is from the context of applied basic science that many future therapies wi

Topics: Anemia; Animals; Brain Diseases; Bronchial Hyperreactivity; Cerebrovascular Disorders; Crohn Disease; Cytokines; Disease Models, Animal; Erythropoietin; Humans; Inflammatory Bowel Diseases; Interleukin-6; Lung Diseases; Lung Diseases, Obstructive; Sarcoidosis; Thrombosis

We evaluated the efficacy and safety of and compliance with rH-EPO (150 U/kg three times a week subcutaneously for up to 12 weeks) for treatment of anemia in childhood Crohn's disease (n = 4). The mean hemoglobin level before rH-EPO therapy was 109 gm/L (10.9 gm/dl) (range, 103 to 115 gm/L). The mean hemoglobin level in the three compliant children increased to 138 gm/L (13.8 gm/dl) after treatment. Response time for the correction of anemia ranged from 6 to 12 weeks (mean, 9.5 weeks). Resolution of symptoms of lethargy, poor appetite, and irritability occurred with correction of the anemia. The only adverse effect observed was transient local pain at the injection site.

Topics: Adolescent; Anemia; Child; Child, Preschool; Chronic Disease; Crohn Disease; Erythropoietin; Hemoglobins; Humans; Infant; Recombinant Proteins; Treatment Outcome

Topics: Anemia; Colitis, Ulcerative; Crohn Disease; Drug Therapy, Combination; Erythropoietin; Hemoglobins; Humans; Iron; Recombinant Proteins

Anemia often complicates Crohn disease and affects quality of life.. To evaluate the efficacy of intravenous iron alone and in combination with erythropoietin for the treatment of anemia associated with Crohn disease.. Double-blind, randomized, placebo-controlled trial with a subsequent open-label phase.. University-based gastroenterology outpatient clinic.. 40 patients with Crohn disease and a hemoglobin concentration of 10.5 g/dL or less.. All patients received intravenous iron saccharate for 16 weeks. During the blinded phase of the trial, they received either erythropoietin or placebo. During the open phase, the erythropoietin dose was increased in non-responders who had received erythropoietin and erythropoietin therapy was initiated in nonresponders who had received placebo.. Response was defined as an increase in hemoglobin concentration of 2 g/dL or more.. 15 of 20 patients in the placebo group (75% [95% CI, 51% to 91%]) and 18 of 19 patients in the erythropoietin group (95% [CI, 74% to 100%]) responded to intravenous iron (P = 0.20). The erythropoietin group had a higher cumulative response rate (P = 0.036) and a more pronounced mean increase in hemoglobin concentration (4.9 g/dL in the erythropoietin group compared with 3.3 g/dL in the placebo group, a difference of 1.6 g/dL [CI, 0.6 g/dL to 2.5 g/dL]; P = 0.004). In the open phase, all 6 previous nonresponders had a response. Hematologic response was associated with improved quality of life (P = 0.03).. Most patients who have anemia associated with Crohn disease respond to intravenous iron alone. Erythropoietin has additional effects on hemoglobin concentrations.

Topics: Adolescent; Adult; Aged; Anemia; Crohn Disease; Double-Blind Method; Drug Therapy, Combination; Erythropoietin; Female; Hemoglobins; Humans; Infusions, Intravenous; Iron; Male; Middle Aged; Quality of Life; Recombinant Proteins

Some patients with inflammatory bowel disease have anemia that is refractory to treatment with iron and vitamins. We examined whether administering iron and recombinant erythropoietin could raise hemoglobin levels in such patients.. Thirty-four patients with inflammatory bowel disease (15 with ulcerative colitis and 19 with Crohn's disease) and anemia refractory to iron therapy (hemoglobin concentrations below 10.0 g per deciliter [6.2 mmol per liter]) were randomly assigned in a prospective, double-blind, 12-week trial to receive either oral iron (100 mg per day) and subcutaneous erythropoietin (150 U per kilogram of body weight twice per week) (n=17) or oral iron and placebo (n=17). The primary measure of efficacy was an increase in hemoglobin levels of more than 1.0 g per deciliter (0.62 mmol per liter). Additional analyses were performed with other patients with inflammatory bowel disease.. The severity of anemia was related to clinical disease activity as well as to in vitro monocyte secretion of interleukin-1 beta, a proinflammatory cytokine. Serum erythropoietin concentrations were increased in 52 randomly selected outpatients with inflammatory bowel disease and anemia, but the concentrations were inadequate in relation to the degree of anemia. Twelve weeks of therapy with recombinant erythropoietin and oral iron increased mean (+/-SE) hemoglobin concentrations from 8.81+/-0.27 g per deciliter (5.47+/-0.17 micromol per liter) to 10.52+/-0.41 g per deciliter (6.5+/-0.25 micromol per liter), whereas hemoglobin concentrations in the placebo group decreased from 8.69+/-0.11 g per deciliter (5.4+/-0.068 micromol per liter) to 7.84+/- 0.33 g per deciliter (4.9+/-0.2 mmol per liter) (P<0.001). After 12 weeks, hemoglobin levels had increased by more than 1.0 g per deciliter in 82 percent of the patients in the erythropoietin group, as compared with 24 percent of those in the placebo group (P=0.002). There were five treatment failures in the placebo group and two in the erythropoietin group (P=0.18); treatment failure was defined as a decrease in hemoglobin levels of more than 2.0 g per deciliter (1.24 micromol per liter) to a value below 8.0 g per deciliter (4.96 micromol per liter) or any decrease to less than 6.5 g per deciliter (4.03 micromol per liter).. In patients with inflammatory bowel disease and anemia refractory to treatment with iron and vitamins, treatment with oral iron and recombinant erythropoietin can raise hemoglobin levels.

Topics: Adolescent; Adult; Anemia; Colitis, Ulcerative; Crohn Disease; Double-Blind Method; Drug Resistance; Erythropoietin; Female; Hematocrit; Humans; Interleukin-1; Iron; Linear Models; Male; Middle Aged; Monocytes; Prospective Studies; Recombinant Proteins; Treatment Outcome

Topics: Adalimumab; Adolescent; Adult; Anemia; C-Reactive Protein; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Erythropoietin; Female; Ferritins; Hemoglobins; Hepcidins; Humans; Inflammatory Bowel Diseases; Infliximab; Interleukin-6; Iron; Male; Middle Aged; Peptide Hormones; Tumor Necrosis Factor-alpha; Young Adult

Topics: Adalimumab; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Crohn Disease; Darbepoetin alfa; Drug Administration Schedule; Erythropoietin; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Platelet Count; Randomized Controlled Trials as Topic; Receptors, Fc; Recombinant Fusion Proteins; Thrombopoietin; Treatment Outcome; Tumor Necrosis Factor-alpha

Topics: Anemia; Crohn Disease; Enteral Nutrition; Erythropoietin; Female; Humans; Male

Topics: Anemia; Crohn Disease; Enteral Nutrition; Erythropoietin; Female; Humans; Male

Anemia is a common and serious complication in patients with inflammatory bowel disease. The present study was dedicated to evaluate the therapeutic efficacy of erythropoietin (EPO) combined with enteral nutrition (EN) in anemic Crohn's disease (CD) patients, in terms of hemoglobin level, treatment success rate, adverse events, and predictor of this therapy.. We performed a prospective study in CD patients. On the basis of hemoglobin level, all enrolled patients were divided into anemic and nonanemic groups. The anemic group was further divided into EPO and non-EPO subgroups, depending on whether EPO was prescribed. Hematological and other parameters were measured initially and in the first 4 weeks after starting treatment.. In total, 109 patients (49 nonanemic and 60 anemic, including 38 EPO and 22 non-EPO) were included. The prevalence of anemia in CD was 55.05%. Age, disease behavior, Crohn's Disease Activity Index scores, C-reactive protein, and erythrocyte sedimentation rate were significantly different between anemic and nonanemic groups. An increase in hemoglobin level and a significant decrease in C-reactive protein level were observed in the EPO treatment group. Treatment success rate was 63.16% in the EPO group, whereas none of patients achieved treatment success in the non-EPO group.. EPO combined with EN can improve the hemoglobin level in anemic CD patients.

Topics: Adolescent; Adult; Anemia; Biomarkers; C-Reactive Protein; Crohn Disease; Dose-Response Relationship, Drug; Enteral Nutrition; Erythropoietin; Female; Humans; Logistic Models; Male; Prospective Studies; Treatment Outcome; Young Adult

Anemia in IBD is the result of a combination of iron deficiency and anemia of chronic disease. Therapy of IBD is relief of inflammation, but the drugs usage may cause the development hemolytic anemia and myelodysplastic syndrome. We studied the effect of basic therapy on the incidence of anemia and assess the impact of modern biological therapies on the main markers of AHZ. A total of 153 patients with ulcerative colitis (UC) and 53 patients with Crohn's disease (CD), which at the time of the study received basic anti-inflammatory therapy for at least 1 year. All patients underwent blood tests, iron metabolism parameters were determined by the level of erythropoietin and G-gepsidina C reactive protein. Modern biological therapy increases the effectiveness of the treatment of anemia in patients with IBD. The use of Remicade gives a quick positive response, which is due to the decrease of gepsidin negative influence on iron metabolism and unlocking the synthesis of erythropoietin. The use of MSCs does not inhibit the synthesis of erythropoietin, and is likely to stimulate erythropoiesis at the erythroblast precursors.

Topics: Anemia, Hemolytic; Anemia, Iron-Deficiency; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antimicrobial Cationic Peptides; C-Reactive Protein; Colitis, Ulcerative; Crohn Disease; Erythroblasts; Erythropoiesis; Erythropoietin; Hepcidins; Humans; In Vitro Techniques; Incidence; Infliximab; Male; Myelodysplastic Syndromes; Risk Factors; Time Factors

Topics: Anemia, Hypochromic; Antirheumatic Agents; Autoimmune Diseases; Blood Loss, Surgical; Christianity; Crohn Disease; Erythropoietin; Folic Acid Deficiency; Hepatitis C, Chronic; Hip Fractures; Humans; Iron; Male; Middle Aged; Paraproteinemias; Premedication; Proteus Infections; Recombinant Proteins; Spondylitis, Ankylosing; Sulfasalazine; Urinary Tract Infections; Vitamins

Topics: Administration, Oral; Anemia; Anemia, Iron-Deficiency; Colitis, Ulcerative; Crohn Disease; Erythropoietin; Ferrous Compounds; Humans; Inflammatory Bowel Diseases; Injections, Subcutaneous; Recombinant Proteins

Intestinal blood loss as well as chronic inflammation are regarded as the most important mechanisms in the pathogenesis of anemia in Crohn's disease. In addition, cytokines such as interleukin-6 can suppress erythropoietin production. This study was performed to investigate the importance of iron status, inflammatory activity, and endogenous erythropoietin concentrations for the development of anemia in Crohn's disease. In 49 consecutive patients with Crohn's disease, hemoglobin, inflammatory activity (Crohn's disease activity index, C-reactive protein, alpha 1-acid glycoprotein), iron status (serum iron, transferrin, transferrin saturation, ferritin), and serum erythropoietin levels were studied. Anemic (Hb < 12.0 g/dl; N = 16) vs nonanemic patients (Hb > or = 12 g/dl; N = 33) showed reduced iron compartments (eg, ferritin 28.7 +/- 12.9 micrograms/liter vs 63.2 +/- 15.0 micrograms/liter, transferrin saturation 6.2 +/- 1.4% vs 11.5 +/- 1.3%, P < 0.01) but no differences in inflammatory activity. An inverse correlation between erythropoietin and hemoglobin concentrations was found (r = -0.62; P < 0.001), but the increase in erythropoietin levels was inadequate to the degree of anemia. There was no correlation between erythropoietin and interleukin-6 serum levels. Four of five anemic patients with hemoglobin below 10.5 g/dl and erythropoietin levels within the normal range were treated with parenteral iron (200 mg iron saccharate in 250 ml NaCl, weekly, intravenously). Two of them additionally received recombinant human erythropoietin (150 units/kg, 3x weekly, subcutaneously). After five weeks all patients had a marked increase in hemoglobin. However, the mean increase in erythropoietin-treated patients was 5.0 g/dl compared to 2.0 g/dl in the patients with iron therapy only.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Anemia; Crohn Disease; Drug Therapy, Combination; Erythropoietin; Female; Ferritins; Humans; Interleukin-6; Iron; Iron Deficiencies; Male; Middle Aged; Recombinant Proteins

Inflammatory bowel disease (IBD) is often associated with anemia. Of 85 patients with IBD, 28 were anemic and had an inadequately low plasma erythropoietin (EPO) concentration. Three patients with a long-standing history of IBD and refractory chronic anemia (hemoglobin values < 10 g/dL, plasma EPO concentrations below 100 mU/mL) were treated with recombinant human EPO, which was administered subcutaneously three times per week at a dose of 200-300 U/kg of body weight. Bone marrow biopsy specimens taken before therapy showed slightly decreased erythropoiesis with a shift of erythroid precursors toward more immature stages. EPO treatment resulted in a marked increase in hemoglobin values in all 3 patients. Bone marrow biopsies after EPO therapy showed quantitatively and qualitatively normal erythropoiesis in all of them. Correction of anemia was followed by improved well-being, and all patients were able to cope much better with their IBD. In all three patients, there was an increase in body weight and their Karnofsky index improved. After a complete workup and exclusion of any other cause for anemia, erythropoietin treatment, although expensive, should be considered in patients with IBD and refractory anemia.

Topics: Anemia, Refractory; Bone Marrow; Colitis, Ulcerative; Crohn Disease; Erythropoietin; Female; Humans; Male; Recombinant Proteins

Topics: Bone Marrow; Colitis, Ulcerative; Crohn Disease; Erythropoiesis; Erythropoietin; Hematologic Diseases; Humans; Leukemia

Topics: Adult; Anemia; Colitis, Ulcerative; Crohn Disease; Erythropoietin; Female; Humans; Male; Sex Factors