P003 Safety Profiles of Different Intravenous Iron Preparations for Therapy of Iron Deficiency Anemia: Preliminary Results From the IBD Subgroup Analysis
Authors: Aksan Ayşegül , Işık Hatice , Tuğal Dilem , Dignass Axel , Stein Jürgen 
Published: December 2019

BACKGROUND:
Iron deficiency anemia (IDA) is an integral part of many disorders and a negative prognostic factor. Although intravenous (IV) iron is increasingly used to treat IDA, some concerns persist regarding its safety. Furthermore, different IV iron compounds on the market have differing safety characteristics. In this ongoing study, we compare the safety of IV iron products to establish whether IV iron carries an increased risk compared to oral iron, and to determine which, if any, has a superior safety profile. Here, we report preliminary results from the inflammatory bowel disease subgroup analysis.

METHODS:
A literature search of PUBMED, SCOPUS, WoS and Cochrane Library was performed up to 07/2019. Primary outcome measure was 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 most common AEs. Bayesian NMA was performed to compare AE rates of each iron therapy relative to all comparators. Deviance information criterion (DIC) statistics were used to compare fixed effect and random effect models.

RESULTS:
8086 distinct publications were found. Of 171 relevant full-text articles on IBD, 5 randomized controlled trials (RCTs) (n = 1143) were eligible, on which Bayesian NMA was performed using a fixed effects model. Low statistical heterogeneity was determined among the studies (I2 = 9%). No statistically significant difference was found between different IV iron products (ferric carboxymaltose, FCM; IS, iron sucrose; IIM, iron isomaltoside) or oral iron. Compared to oral iron; OR = 0.69, 95% CrI [0.29;1.7] for FCM, OR = 0.52, 95% CrI [0.22;1.2] for IS, OR = 1.5, 95% CrI [0.80;3.1] for IIM. Compared to FCM; OR = 0.74, 95% CrI [0.45;1.2] for IS, OR = 2.2,95% CrI [0.74;6.7] for IIM. Compared to IS; OR = 0.1.3, 95% CrI [0.82;2.2] for IS, OR = 3.0, 95% CrI [1.0;9.1] for IIM. Compared to IIM; OR = 0.45, 95% CrI [0.15;1.3] for FCM, OR = 0.33, 95% CrI [0.11;1.0] for IS. The most common AEs were: headache (1.8%) and transient hyperferritinemia (1.8%) for FCM; headache (1.5%), hyperferritinemia and rigors (both 1.2%) for IS; flushing (2.7%), hypersensitivity and hepatic enzyme increase (both 1.8%) for IIM; diarrhea (8.0%) and abdominal pain (7.7%) for oral iron. Hypophosphatemia, a much-debated complication of IV iron treatment, was reported in only one RCT of FCM, in this case transient and clinically asymptomatic. Six SAEs were recorded; 1/381 for FCM, 1/223 for IIM and 5/238 for oral iron (included in the calculation of total AE rate for the main analysis). No eligible RCTs were found for ferumoxytol or iron dextran.

CONCLUSION(S):
None of the IV iron products were found to be associated with an increased risk of adverse or serious adverse events compared to oral iron, and all showed similarly low rates of adverse events. However, the safety profiles of different IV iron preparations were found to differ: Whereas headaches were more common in patients receiving FCM or IS, IIM was more frequently associated with hypersensitivity reactions or raised levels of hepatic enzymes. On this evidence, therefore, while FCM, IS and IIM are all safe, they have differing safety characteristics which should be borne in mind when choosing suitable therapy options.