P043 Update of a network meta-analysis of efficacy and safety of different intravenous iron compounds in patients with IBD and anemia
Authors: Ayşegül Aksan , Hatice Işık , Heinfried Radeke , Axel Dignass , Jürgen Stein 
Published: July 2019

BACKGROUND:
Iron deficiency anemia (IDA) is a frequent complication of inflammatory bowel disease (IBD) associated with reduced quality of life and increased hospitalization rates. Modern intravenous iron compounds have been demonstrated to be safe and effective in IBD patients, facilitating rapid correction of hemoglobin levels and repletion of body iron stores. International guidelines recommend intravenous (IV) administration of iron in IBD patients with IDA. Compounds currently approved for IDA in IBD are ferric carboxymaltose (FCM), ferumoxytol (FOX), iron sucrose/saccharate (IS), iron isomaltoside (ISM) and iron dextran (IDX). Slight variances in the core size and the composition and density of the surrounding carbohydrate cause variations in the efficacy and tolerability of IV iron formulations. Here, we searched for new data to augment a first network metaanalysis (NMA) and systematic review of IV iron preparations in IBD carried out in 2016 (PROSPERO registration number: 42016046565).

METHODS:
Using the same search methodology, we performed a new search using the PubMed, Scopus, Web of Science and Cochrane databases to identify articles published since the original systematic review and NMA, i.e., between July 2016 and August 2018. Primary outcome measure was hematopoietic response (% of patients), defined as hemoglobin (Hb) normalization or Hb increase of ≥2 g/dL. Secondary outcomes included number of adverse events (AEs) as percentage of safety population.

RESULTS:
Our search criteria produced 151 studies. We identified 4 prospective observational studies (2 FCM and 2 ISM) not included in the original systematic review and NMA, making 18 studies in total. Eligible studies evaluating FOX were not found. Since no additional RCTs eligible for the NMA were identified, the NMA of 4 studies could not be augmented. In total, the updated systematic review included 7 studies with 798 patients for FCM, 2 studies with 78 patients for IDX, 8 studies with 508 patients for IS, and 3 studies with 423 patients for ISM as infusion or bolus injection. Overall response rates were FCM; 599/798 (78%), IDX; 33/78 (42%), IS; 344/508 (68%), ISM; 265/423 (63%). In general, all IV iron products were reported to be well tolerated with some risks of AEs. Overall rates of AEs and serious AEs were 66/836 (7.9%) and 1/836 (0.1%) for FCM; 10/83 (12%) and 0/83 for IDX; 72/471 (15.3%) and 1/471 (0.2%) for IS; 54/454 (12.7%) and 5/424 (1.2%) for ISM, respectively. Only FCM was significantly more effective than oral iron (Odds Ratio = 1.9, 95% CrI [1.1;3.2]). IS and ISM also had better response rates than oral iron but without statistical significance. p-values of <0.05 for the node-splitting analysis of the Bayesian analyses indicated insignificant inconsistency.

CONCLUSION(S):
Our findings indicate that FCM remains 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. The totality of evidence showed that further studies are unlikely to overturn this result. Nevertheless, further studies are needed to improve the level of evidence available to establish the comparative efficacy of different IV iron compounds in IBD patients with IDA.