Abstract
Background
Current ECCO guidelines state that intravenous (IV) iron should be considered first-line treatment in patients with clinically active IBD, previous intolerance to oral iron, Hb below 100 g/l and patients who need erythropoiesis-stimulating agents. Several different IV iron products are available with differing therapeutic effectiveness and tolerability. In this ongoing study, we compare their safety profiles to establish whether any IV iron carries an increased risk compared with other IV iron products or with oral iron, and to determine which, if any, has a superior safety profile. We report preliminary results from an IBD subgroup analysis.
Methods
We performed a systematic review and network meta-analysis (NMA), searching PUBMED, SCOPUS, WoS and Cochrane Library up to July 2019. The primary outcome measure was the pooled total of drug-related adverse events (AEs) and serious AEs (SAEs) in proportion to the safety population. The secondary outcome measure was identification of the most common AEs.
Results
8086 distinct publications were found. Of 171 relevant full-text articles on IBD, 5 RCTs (n = 1143) were eligible. Bayesian NMA was performed using a fixed effects model. Low statistical heterogeneity was determined (I2= 9%). AE rates did not differ significantly between the different IV iron products (ferric carboxymaltose/FCM; iron sucrose/IS; iron isomaltoside/IIM) or oral iron. Compared with 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 with FCM; OR=0.74, 95% CrI [0.45;1.2] for IS, OR=2.2, 95% CrI [0.74;6.7] for IIM. Compared with IS; OR=0.1.3, 95% CrI [0.82;2.2] for IS, OR=3.0, 95% CrI [1.0;9.1] for ISM. Compared with 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 hyperferritinaemia (1.8%) for FCM; headache (1.5%), hyperferritinaemia and rigors (both 1.2%) for IS; flushing (2.7%), hypersensitivity and hepatic enzyme increase (both 1.8%) for IIM; diarrhoea (8.0%) and abdominal pain (7.7%) for oral iron. Hypophosphataemia was reported in only 1 RCT of FCM, here transient and clinically asymptomatic. Seven SAEs were recorded; 1/381 for FCM, 1/223 for IIM and 5/238 for oral iron.
Conclusion
None of the IV iron products was associated with an increased risk of AEs or SAEs compared with oral iron and all showed similarly low rates of AEs. However, their safety profiles differed: Whereas with FCM or IS, headaches were most commonly reported, IIM was more frequently associated with hypersensitivity reactions or increase in hepatic enzymes. On this evidence, while FCM, IS and IIM are all safe, their differing safety characteristics should be considered in therapeutic decision-making.
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