Iron deficiency anaemia (IDA) is a common and important complication of inflammatory bowel disease (IBD) associated with reduced quality of life and increased hospitalisation rates. Not only has inflammation been shown to limit the absorption and efficacy of oral iron, but oral iron may exacerbate bowel inflammation in IBD. International guidelines recommend intravenous (IV) administration of iron in IBD patients with IDA. Compounds currently approved for IDA in IBD are ferric carboxymaltose (FCM), iron sucrose/saccharate (IS), iron isomaltoside (ISM) and iron dextran (ID).Methods:
We compared the efficacy and safety of different IV iron compounds approved to treat IDA in IBD patients using a network meta-analysis (NMA) and systematic review. In June 2016, PUBMED, SCOPUS, Web of Science and Cochrane databases were searched for trials analysing IV iron therapy of IDA in IBD with an observation time of ≥2 weeks and published in English. Primary outcome measure was haematopoietic response (% of patients), defined as haemoglobin (Hb) normalisation or increase of ≥2 g/dL. Secondary outcomes included number of adverse events (AEs) as percentage of safety population (AEs). Bayesian NMA was performed after assessment of eligible studies using the Cochrane Risk of Bias tool in RevMan. Response rates and odds ratios (ORs) were assessed. All analyses were conducted using R version 3.3.1 with package gemtc. We used deviance information criterion (DIC) statistics to compare fixed effect (FEM) and random effect models (REM) (DIC: 22.471 for FEM versus 23.027 for REM). Bayesian NMA was expressed as ORs based on response rate with 95% credible intervals (CrIs).Results:
Of 3568 studies in total, after removal of duplications and detailed review, 6 RCTs remained with observation times of 6 to 20 weeks (used for the NMA) and 9 other trials (included in systematic review only). Four RCTs compared FCM, IS or ISM versus oral iron, one compared FCM versus IS, and one IS versus IS combined with erythropoietin (IS + EPO). FCM was significantly more effective than oral iron (OR = 1.9, 95% CrI [1.2–3.2]). For other IV formulations, no statistical significance was found versus oral iron (OR = 1.3, 95% CrI [0.79–2.2] for IS, OR = 1.3, 95% CrI [0.8–2.1] for ISM, OR = 4.5, 95% CrI [0.71–43.0] for IS + EPO). Rank probabilities of the 5 treatments predictably showed IS + EPO to be most effective, followed by FCM, IS, ISM and oral iron. AEs occurred at rates of 12.3% (47/381), 18.1% (59/326), and 17.0% (38/223), and SAEs at 0.3% (1/381), 0.3% (1/326), 0.4% (1/223), for FCM, IS and ISM, respectively. For oral iron, AE rate was 30.2% (73/242), and SAE rate 2.1% (5/242).Conclusions:
FCM was shown to be the most effective IV iron formulation as monotherapy, followed by iron sucrose. In addition, FCM tended to have a better safety profile, with fewer AEs.