Background: Iron deficiency anaemia (IDA) is a frequent 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. ECCO guidelines recommend intravenous (IV) administration of iron in IBD patients with IDA. IV Compounds currently approved for IDA in IBD are ferric carboxymaltose (FCM), iron sucrose/saccharate (IS), iron isomaltoside (ISM) and iron dextran (IDX).
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 with an observation time ≥4 weeks analysing IV iron therapy of IDA in IBD and published in English. Outcome measures were haematopoietic response (% of patients), defined as haemoglobin (Hb) normalisation or increase of ≥2g/dL and no. of AEs as % of safety population. Bayesian NMA was performed after assessment of eligible studies using Cochrane's Risk of Bias tool in RevMan and expressed as ORs based on response rate with 95% credible intervals (CrIs). Analyses were conducted using R vers. 3.3.1 with package gemtc.
Results: From 1894 papers in total, after duplication removal and detailed review, 15 eligible studies were included: 6 RCTs (NMA) and 9 other studies (systematic review only). No eligible RCTs were found for IDX. Bayesian NMA was performed on the 6 eligible RCTs (1182 patients): Four RCTs compared FCM, IS or ISM vs. oral iron, one compared FCM vs. IS, and one IS vs. IS plus erythropoietin (IS+EPO). FCM was significantly more effective than oral iron (OR=1.9, 95% CrI [1.2;3.2]). For other IV iron, no statistical significance was found vs. 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 five treatments showed the most effective IV monotherapy to be FCM. IS+E combination therapy was most effective overall. The systematic review (1765 patients) showed overall response rates of 401/505 (79%) for FCM, 344/508 (68%) for IS, 147/219 (67%) for ISM and 33/78 (42%) for IDX. Drug-related AEs occurred at pooled rates of 12.0%, 15.3%, 12.0% and 17.0%, SAEs at 0.2%, 0.2%, 0.0%, 0.4%, for FCM, IS, IDX and ISM, respectively. For oral iron, AE rate was 23.2% (82/353), and SAE rate 1.4% (5/353).
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 than IS or ISM, with fewer AEs.