P044 The comparative safety of different intravenous iron preparations in inflammatory bowel disease: A systematic review and network meta-analysis
Authors: Ayşegül Aksan , Hatice Işık , Karima Farrag , Axel Dignass , Jürgen Stein 
Published: July 2019

BACKGROUND:
Anemia is the most frequent systemic complication of IBD, with a prevalence of up to 74%. Oral iron compounds are of limited efficacy in IBD, due to gastrointestinal side effects and poor compliance. Modern intravenous (IV) iron compounds have been demonstrated to be safe and effective in IBD patients and are recommended by international guidelines. However, some safety concerns remain. Compounds currently approved for iron deficiency anemia (IDA) in IBD are ferric carboxymaltose (FCM), ferumoxytol (FOX), iron sucrose/saccharate (IS), iron isomaltoside (ISM) and iron dextran (IDX). We compared the tolerability of different IV iron compounds used to treat IDA in IBD patients in a systematic review and network metaanalysis (NMA).

METHODS:
A literature search was performed in PUBMED, SCOPUS, Web of Science and the Cochrane Library to identify studies. No date restrictions were imposed, the last search was completed August 2018. Primary outcome measure was the pooled total of drug-related adverse events (AEs) and serious adverse events (SAEs) in proportion to the safety population. Secondary outcome measure was identification of the commonest adverse events. Bayesian NMA was performed using Markov Chain Monte Carlo Methods to calculate the tolerability of each iron therapy relative to all comparators. Heterogeneity was tested with I2, using the Higgins and Thompson method to indicate the percentage of variance attributable to study heterogeneity, and a random effect model (ROM) was used for analysis. Results were presented as Odds Ratios (OR) in relation to response rate to iron treatment. Bias risk of eligible studies was assessed using the Cochrane Collaboration’s Risk of Bias tool in Review Manager (RevMan 5).

RESULTS:
2,730 papers were found. After duplication removal and detailed review, 25 eligible studies were included: 4 RCTs (NMA) and 21 others (systematic review only). No eligible studies for FOX and no RCTs for IDX were found. Bayesian NMA was performed on 4 eligible RCTs (n = 1,052). ROM showed no evidence of inconsistency between direct and indirect evidence in all networks; all p-values were statistically insignificant at 5%. The ROM fit the data adequately with no evidence of inconsistency (DIC = 15.7). No statistically significant difference was found between different IV iron products or oral iron (vs oral iron: OR = 0.87, 95% CrI [0.43;1.7] for FCM, OR = 0.80, 95% CrI [0.36;1.8] for IS, OR = 1.5, 95% CrI [0.64;3.7] for ISM). The systematic review (n = 2,619) showed overall AE rates of 83/1,028 (8.1%) for FCM, 78/481 (16.2%) for IS, 89/475 (18.7%) for ISM and 10/83 (12%) for IDX. Drug-related SAEs occurred at pooled rates of 0.1%, 2.2%, 0.0%, 1.1%, for FCM, IS, IDX and ISM, respectively. For oral iron, AE/SAE rates were 22.6%, 1.4%.

CONCLUSION(S):
While the systematic review indicates FCM to be associated with fewer adverse events, its statistical significance remains unproven due to the lack of data from randomised controlled trials. Although hypophosphatemia has been reported to be associated with IV iron administration, especially FCM, it was temporary and asymptomatic, if reported at all. There were no reports of hypophosphatemia-related bone manifestations. Further comprehensive trials are needed to draw conclusions concerning the comparative safety of different IV iron substances.