fumarates and Anemia--Iron-Deficiency

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

At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer.. In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland.. This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity.. ClincalTrials.gov: NCT02243735 .

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Clinical Protocols; Colorectal Neoplasms; Dietary Supplements; Female; Ferric Compounds; Ferrous Compounds; Fumarates; Hematinics; Humans; Infusions, Intravenous; Male; Maltose; Middle Aged; Preoperative Care; Treatment Outcome; Young Adult

Infants in developing countries require early dietary interventions to prevent nutritional deficiencies, above all protein, energy, iron and zinc. To what extent these interventions may affect the fatty acid (FA) status is still unknown.. To examine and compare the effects of 2 micronutrient "sprinkles" supplementations (iron 12.5 mg + folic acid 150 microg, iron/folate and iron 12.5 mg + folic acid 150 microg + zinc 5 mg + vitamins A, C and D3, mineral/micronutrient [MMN]) versus placebo on the FA status of Cambodian infants.. A total of 204 infants age 6 mo and living in Kompong Chhnang Province, Cambodia, were randomly assigned to receive daily supplementation of MMN (n = 68) and iron/folate (n = 68) or placebo (n = 68) for a 12-mo period in powder form as sprinkles. At the end of the intervention period, FAs in the range of 16 to 24 C were determined in blood drops absorbed on a strip collected from 182 subjects, and values among the 3 intervention subgroups and those of 21 Italian 18-mo-old, normal-growing infants as the reference group were compared.. At the end of the supplementation trial, higher levels of the 2 essential FAs (EFAs) (linoleic acid, 18:2n-6, and alpha-linolenic acid, 18:3n-3) were found in the MMN group. No differences occurred for the major longer chain derivatives of both EFAs arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). In MMN supplemented Cambodians, blood levels of linoleic acid approached those of Italian infants, and in addition their alpha-linolenic acid levels were improved. Cambodian infants, mostly still breast-fed through the second year of life, showed significantly higher levels of long-chain derivatives of both the n-6 and the n-3 series compared with Italians.. Supplementation with iron, folic acid, zinc and vitamins was associated with an increase of linoleic acid and alpha-linolenic acid levels in Cambodian infants versus placebo, without significant changes in the concentrations of their longer chain derivatives, resulting in a FA status closer to Italian counterparts for the essential polyunsaturated FA levels. The iron/folate-treated infants showed no differences compared with the other 2 groups. Studies are needed to differentiate the potential effects of the supplemented micronutrients on the FA status.

Topics: alpha-Linolenic Acid; Anemia, Iron-Deficiency; Ascorbic Acid; Cambodia; Child Development; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Fumarates; Gluconates; Humans; Infant; Iron Compounds; Italy; Linoleic Acid; Longitudinal Studies; Male; Micronutrients; Polysaccharides; Vitamin A

It is a common belief among women that iron compounds have unpleasant gastrointestinal side effects.. To assess the gastrointestinal side effects of iron prophylaxis in pregnancy.. A randomized, double-blind study comprising 404 healthy pregnant women allocated to four groups taking ferrous iron supplement (as fumarate) in doses of 20 (n = 99), 40 (n = 100), 60 (n = 102) and 80 mg (n = 103) daily from 18 weeks of gestation to delivery. Iron supplement was predominantly taken at bedtime. Gastrointestinal symptoms (nausea, vomiting, epigastric pain, eructation, pyrosis, meteorism, borborygmi, colic pain, flatulence, constipation, thin feces, diarrhea), black feces, and use of laxatives were recorded by interview at 18, 32 and 39 weeks of gestation.. The frequencies of gastrointestinal symptoms were not significantly different in the four iron supplement groups either at inclusion or at 32 and 39 weeks of gestation and thus not related to the iron dose.. This study shows that a supplement of 20-80 mg ferrous iron (as fumarate), taken between meals, has no clinically significant gastrointestinal side effects. The implementation of iron prophylaxis to pregnant women should not be compromised by undue concern of non-existing side effects.

Topics: Administration, Oral; Adult; Anemia, Iron-Deficiency; Anticarcinogenic Agents; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fumarates; Gastrointestinal Diseases; Humans; Iron, Dietary; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Trimesters

Topics: Anemia; Anemia, Hypochromic; Anemia, Iron-Deficiency; Drug Therapy; Female; Ferrous Compounds; Fumarates; Humans; Iron; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Puerperal Disorders