Systematic Review and Meta-Analysis of Hypersensitivity Reactions after High-dose Intravenous Iron

Serious or severe hypersensitivity reactions (HSRs) are uncommon with modern intravenous (IV) iron formulations but, when occurring, can be life-threatening or even fatal. We synthesized the available data on serious or severe HSR incidence for ferric derisomaltose (FDI), ferric carboxymaltose (FCM), and ferumoxytol (FER), as treatments for iron deficiency anemia (IDA). A systematic literature review for randomized controlled trials (RCTs) was conducted in PubMed, Embase, and CENTRAL. From eligible RCTs, proportions of patients experiencing serious or severe HSR post-IV iron administration, reported using the Standardized Medical Dictionary for Regulatory Activities Query (SMQ) for anaphylactic reaction, were extracted. A Bayesian random-effects model was used to obtain posterior distributions of HSR incidence and Surface Under the Cumulative Ranking (SUCRA) plots, ranking formulations by HSR likelihood. Any serious or severe HSR falling under the anaphylactic reaction SMQ was experienced by 0.14% of patients with FDI, 0.59% of patients with FCM, and 0.50% of patients with FER. The meta-analysis indicated a reduced serious or severe HSR risk with FDI versus FCM (0.21 [95% credible interval [CrI] 0.03 to 1.73) and FER (0.07 [95% CrI 0.00 to 1.93]). SUCRA plots showed that the likelihood of FDI having the lowest serious or severe HSR incidence was 91.4% (FCM: 4.5%; FER: 4.2%). This meta-analysis of data from RCTs, including 11,268 patients, represents a comprehensive analysis of serious or severe HSRs among the available high-dose IV iron formulations, detailing an important facet of formulations' safety profiles.