ferric-oxide--saccharated and Colitis--Ulcerative

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

Anemia is a frequent complication of ulcerative colitis, and is frequently caused by iron deficiency. Oral iron supplementation displays high rates of gastrointestinal adverse effects. However, the formulation of sucrosomial iron (SI) has shown higher tolerability. We performed a prospective study to compare the effectiveness and tolerability of oral SI and intravenous ferric carboxy-maltose (FCM) in patients with ulcerative colitis in remission and mild-to-moderate anemia. Patients were randomized 1:1 to receive 60 mg/day for 8 weeks and then 30 mg/day for 4 weeks of oral SI or intravenous 1000 mg of FCM at baseline. Hemoglobin and serum levels of iron and ferritin were assessed after 4, 8, and 12 weeks from baseline. Hemoglobin and serum iron increased in both groups after 4 weeks of therapy, and remained stable during follow up, without significant treatment or treatment-by-time interactions (

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Anemia, Iron-Deficiency; Colitis, Ulcerative; Comparative Effectiveness Research; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Hematinics; Hemoglobins; Humans; Iron; Male; Maltose; Middle Aged; Prospective Studies; Treatment Outcome

Iron deficiency is a common complication in patients with IBD and oral iron therapy is suggested to exacerbate IBD symptoms. We performed an open-labelled clinical trial to compare the effects of per oral (PO) versus intravenous (IV) iron replacement therapy (IRT).. The study population included patients with Crohn's disease (CD; N=31), UC (N=22) and control subjects with iron deficiency (non-inflamed, NI=19). After randomisation, participants received iron sulfate (PO) or iron sucrose (IV) over 3 months. Clinical parameters, faecal bacterial communities and metabolomes were assessed before and after intervention.. Both PO and IV treatments ameliorated iron deficiency, but higher ferritin levels were observed with IV. Changes in disease activity were independent of iron treatment types. Faecal samples in IBD were characterised by marked interindividual differences, lower phylotype richness and proportions of Clostridiales. Metabolite analysis also showed separation of both UC and CD from control anaemic participants. Major shifts in bacterial diversity occurred in approximately half of all participants after IRT, but patients with CD were most susceptible. Despite individual-specific changes in phylotypes due to IRT, PO treatment was associated with decreased abundances of operational taxonomic units assigned to the species. Shifts in gut bacterial diversity and composition associated with iron treatment are pronounced in IBD participants. Despite similar clinical outcome, oral administration differentially affects bacterial phylotypes and faecal metabolites compared with IV therapy.. clinicaltrial.gov (NCT01067547).

Topics: Administration, Intravenous; Administration, Oral; Anemia, Iron-Deficiency; Colitis, Ulcerative; Crohn Disease; Feces; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Gastrointestinal Microbiome; Glucaric Acid; Hematinics; Humans; Iron Deficiencies; Metabolome; Quality of Life; RNA, Ribosomal, 16S

Iron therapy may reinforce intestinal inflammation by catalysing production of reactive oxygen species. The effects of oral ferrous fumarate and intravenous iron sucrose on clinical disease activity and plasma redox status were investigated in patients with inflammatory bowel disease (IBD).. Nineteen patients with iron deficiency anaemia and Crohn's disease (11) or ulcerative colitis (8) were included in a crossover study. The patients were randomly assigned to start treatment with ferrous fumarate (Neo-fer) 120 mg orally once daily or iron sucrose (Venofer) 200 mg intravenously 3 times during a period of 14 days. Clinical disease activity assessment and blood and faecal analysis were performed on days 1 and 15.. Following oral ferrous fumarate clinical disease activity (p=0.037), general well-being score (i.e. patients felt worse) (p=0.027) and abdominal pain score (p=0.027) increased, while no changes were seen following iron sucrose treatment. C-reactive protein (CRP) and faecal calprotectin were unchanged after both treatments. As compared with iron sucrose, ferrous fumarate increased Crohn's disease activity index (CDAI) scores of general well-being (p=0.049), whereas alterations in clinical disease activity (p=0.14) and abdominal pain score (p=0.20) did not differ. Ferrous fumarate did not significantly alter plasma malondialdehyde (MDA) or plasma antioxidants. Iron sucrose increased plasma MDA (p=0.004) and decreased plasma vitamin C (p=0.017) and betacarotene (p=0.008).. Oral ferrous fumarate, but not intravenous iron sucrose, increased clinical disease activity in IBD patients. Intravenous iron sucrose increased intravascular oxidative stress.

Topics: Administration, Oral; Adolescent; Adult; Antioxidants; Biomarkers; C-Reactive Protein; Chromatography, High Pressure Liquid; Colitis, Ulcerative; Crohn Disease; Cross-Over Studies; Feces; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferrous Compounds; Follow-Up Studies; Glucaric Acid; Humans; Injections, Intravenous; Leukocyte L1 Antigen Complex; Male; Malondialdehyde; Middle Aged; Severity of Illness Index; Treatment Outcome

Intravenous iron and erythropoietin have been shown to be effective in Crohn's disease-associated anemia. The aim of this study was to test the sequential treatment of anemia in ulcerative colitis with intravenous iron in the first phase and erythropoietin in the second.. Twenty patients with ulcerative colitis-associated anemia (hemoglobin < or = 10.5 g/dl) entered this open-label trial. In the first phase all patients received intravenous iron saccharate for 8 weeks. A response was defined as an increase in hemoglobin > or = 2.0 g/dl; a final hemoglobin >10.5 g/dl was regarded as full response, < or = 10.5 g/dl as partial response. A hemoglobin increase < 2.0 g/dl was regarded as nonresponse. In the second phase (n = 4) erythropoietin was initiated in patients without response. Patients with partial response were continued on iron saccharate for another 8 weeks.. During the first phase the hemoglobin increased from 8.3 to 11.9 g/dl (mean hemoglobin difference 3.6+/-2.3 g/dl, p < 0.001). Fifteen patients (75%) showed a full response (mean hemoglobin difference 4.5+/-1.5 g/dl), 1 (5%) a partial response (hemoglobin difference 2.1 g/dl) and 4 no response (mean hemoglobin difference 0.4+/-1.8 g/dl) with a need for blood transfusions in a single patient. In the second study phase erythropoietin was highly effective in previous nonresponders (mean hemoglobin difference 3.3+/-1.9 g/dl). The single patient with partial response had a minor hemoglobin increase (hemoglobin difference 1.0 g/dl).. Most patients with ulcerative colitis-associated anemia improve on intravenous iron alone. Erythropoietin is effective in those who do not respond.

Topics: Adult; Anemia, Iron-Deficiency; C-Reactive Protein; Colitis, Ulcerative; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Glucocorticoids; Hemoglobins; Humans; Immunosuppressive Agents; Injections, Intravenous; Male; Recombinant Proteins; Reticulocyte Count; Treatment Outcome

To evaluate trends in diagnosis and management of iron deficiency anemia using a large national children's hospital database in pediatric patients admitted with inflammatory bowel disease (IBD).. In this retrospective multicenter cohort study, we used the Pediatric Health Information System de-identified administrative database. Patients age <21 years with ≥2 admissions with International Classification of Disease, Ninth Revision and Tenth Revision codes for Crohn's disease or ulcerative colitis from 2012 to 2018 were included. We extracted data regarding diagnoses of anemia and/or iron deficiency, and receipt of oral iron, intravenous (IV) iron, and/or blood transfusion. Data were analyzed descriptively.. We identified 8007 unique patients meeting study criteria for a total of 28 260 admissions. The median age at admission was 15.4 years. A diagnosis of anemia was documented in 29.8% of admissions and iron studies were performed in 12.6%. IV iron was given in 6.3% of admissions and blood transfusions in 7.4%. The prevalence of the diagnosis of anemia among IBD admissions increased from 24.6% in 2012 to 32.4% in 2018 (P < .0001). There was a steady increase in the proportion of IBD admissions that used IV iron, from 3.5% in 2012 to 10.4% in 2018 (P < .0001), and the proportion of admissions with red cell transfusions decreased over time from 9.4% to 4.4% (P < .0001).. Iron deficiency anemia is prevalent among pediatric patients with IBD admitted to US children's hospitals. From 2012 to 2018, there was an increase in the use of inpatient IV iron for the treatment of iron deficiency anemia and a decrease in transfusions.

Topics: Adolescent; Anemia, Iron-Deficiency; Blood Transfusion; Child; Child, Preschool; Cohort Studies; Colitis, Ulcerative; Crohn Disease; Female; Ferric Compounds; Ferric Oxide, Saccharated; Hematinics; Hospitalization; Humans; Infant; Iron-Dextran Complex; Male; Prevalence; Retrospective Studies; Young Adult

Anemia is a common complication of inflammatory bowel diseases (IBD), as well as a predictor of poor outcomes. The aim of this study was to determine the prevalence of anemia over time and the management of moderate to severe anemia at a tertiary referral IBD center.. We retrospectively reviewed the occurrence of anemia at the time of referral or diagnosis and during follow-up at the McGill University Health Centre IBD center. Consecutive patients presenting with an outpatient visit between July and December 2016 and between December 2018 and March 2019 were included. Disease characteristics, biochemistry and medical management, including the need for intravenous iron therapy were recorded.. 1,356 Crohn's disease (CD) and 1,293 ulcerative colitis (UC) patients [disease duration: 12 (IQR: 6-22) and 10 (IQR: 5-19) years respectively] were included. The prevalence of moderate to severe anemia at referral/diagnosis (15.4% and 8.5%) and during follow-up (11.1% and 8.1%) were higher in CD than in UC patients. In CD, previous resective surgery, perianal disease and elevated C-reactive protein (CRP) at assessment, while in UC steroid therapy, an elevated CRP and fecal calprotectin at assessment were associated with anemia in a multivariate analysis. Anemia improved by >2g/dL in 56.5% after 4-6 weeks (intravenous iron dose >1000 mg in 87% of patients).. Anemia occurred frequently in this IBD cohort, at referral to the center and during follow-up, and contributes to the burden of IBD in referral populations. Most patients were assessed for anemia regularly and with accurate anemia workup; however, the targeted management of moderate to severe anemia was suboptimal.

Topics: Anemia; Colitis, Ulcerative; Crohn Disease; Female; Ferric Oxide, Saccharated; Hematinics; Humans; Infusions, Intravenous; Male; Prevalence; Quebec; Retrospective Studies; Severity of Illness Index; Tertiary Care Centers; Time Factors

Iron deficiency anaemia frequently complicates inflammatory bowel disease (IBD) in children and adults. Oral iron may exacerbate gastrointestinal symptoms and absorption may be insufficient in intestinal inflammation. Even where oral iron is successful, repletion of iron stores can be unacceptably slow. Intravenous iron compounds were in the past associated with serious adverse reactions and historically were considered a last resort in children. New generation preparations have a safer profile in adults, although reluctance to use them in children may persist, where safety data are lacking. We investigate the safety and efficacy of ferric carboxymaltose and iron sucrose in children.. We retrospectively identified all children with IBD who received parenteral iron over a 38-month period in a single regional referral centre. Safety, tolerability and adverse events were established by case note review. Efficacy was assessed by change in haematinic indices pre- and post-treatment.. Forty-one children (18 male; median age 14 years, range 3-17) received a total of 104 iron infusions. Of these, 44% (18) had Crohn's disease; 56% (23) ulcerative colitis. Thirty-five received ferric carboxymaltose, seven iron sucrose and one both. Three children developed mild rash post infusion which resolved quickly with chlorphenamine. Mean increase in haemoglobin was 2.5 g dl. New generation parenteral iron preparations are safe, well tolerated and efficacious in children with iron deficiency anaemia and IBD.

Topics: Adolescent; Anemia, Iron-Deficiency; Child; Child, Preschool; Colitis, Ulcerative; Crohn Disease; Female; Ferric Compounds; Ferric Oxide, Saccharated; Hemoglobins; Humans; Infusions, Intravenous; Male; Maltose; Retrospective Studies; Transferrin

Inflammatory bowel disease (IBD)-associated anaemia usually responds to intravenous iron. If not, additive treatment with erythropoietin has been proposed. The objective of the present retrospective study was to evaluate the effectiveness of treatment with iron sucrose alone.. Sixty-one patients with IBD and anaemia (average haemoglobin 97 g/L) were treated with iron sucrose (iron dose 1.4 +/- 0.5 g). The indications for iron sucrose were poor response and/or intolerance to oral iron. Treatment response was defined as an increase in haemoglobin of > or = 20 g/L or to normal haemoglobin levels (> or = 120 g/L). Two independent investigators retrospectively assessed laboratory variables, clinical findings, and concomitant medication.. Two patients were transferred to other hospitals after treatment and therefore could not be evaluated. Fifty-four of the remaining 59 patients (91%) responded within 12 weeks. Sixty percent of the patients had responded within 8 weeks. Five patients had no or only a partial response to iron sucrose of which three had prolonged gastrointestinal blood losses. Eight patients with normal or elevated levels of ferritin could be considered to have anaemia of chronic disease, and all of them responded to iron sucrose. During a follow-up period of 117 +/- 85 (4-291) (mean +/- s (standard deviation) (range)) weeks 19 patients (32%) needed at least one second course of iron sucrose because of recurrent disease.. Anaemia associated with IBD can be successfully treated with intravenously administered iron sucrose, provided that bowel inflammation is treated adequately and enough iron is given. Treatment with iron sucrose is safe. Follow-up of haemoglobin and iron parameters to avoid further iron deficiency anaemia is recommended.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Colitis, Ulcerative; Crohn Disease; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infusions, Intravenous; Male; Middle Aged; Retreatment; Retrospective Studies; Sucrose; Treatment Outcome