Clinical data for intravenous iron - debunking the hype around hypersensitivity

Abstract

Background: Reluctance to use intravenous (IV) iron for the treatment of iron deficiency continues due to a perceived high risk of severe hypersensitivity reactions (HSRs). Additionally, it has been hypothesized that 'dextran-derived' IV iron products (e.g., ferumoxytol [FER] and ferric derisomaltose/iron isomaltoside 1000 [FDI]) have a higher risk of severe HSRs than 'non-dextran-derived' products (e.g., ferric carboxymaltose [FCM] and iron sucrose [IS]). In the present analysis, HSR data from head-to-head randomized controlled trials (RCTs) with IV iron products were evaluated to determine if differences in safety signals are present among these IV iron formulations.

Study design and methods: Reported serious or moderate-to-severe HSR incidence data from five RCTs (FIRM; FERWON-NEPHRO/-IDA; PHOSPHARE-IDA04/-IDA05) were used to calculate risk differences with 95% confidence intervals (CIs) for FER, FCM, FDI, and IS. The rates and risk differences for these HSRs were compared.

Results: The analysis included data for 5247 patients: FER (n = 997), FCM (n = 1117), FDI (n = 2133) and IS (n = 1000). Overall rates of serious or moderate to severe HSRs were low (0.2%-1.7%). The risk differences (95% CIs) showed small differences between the IV iron formulations: FER versus FCM, -0.1 (-0.8 to 0.6); FDI versus IS, 0.1 (-0.3 to 0.5); FDI versus FCM, -0.9 (-3.7 to 1.9).

Conclusion: RCT evidence confirms a low risk of serious or moderate to severe HSRs with newer IV iron formulations and no significant differences among existing commercially available products. Thus, RCT data show that the supposed classification of dextran-derived versus non-dextran-derived IV iron products has no clinical relevance.

Fig. 1.

The risk of serious or moderate to severe HSRs associated with the use of IV iron products – data from the FIRM, FERWON, and PHOSPHARE studies. CI = confidence interval; FCM = ferric carboxymaltose; FDI = ferric derisomaltose/iron isomaltoside 1000; FER = ferumoxytol; HSR = hypersensitivity reaction; IS = iron sucrose.

Fig. 2.

Algorithm for the management of immediate infusion reactions. Adapted from: Rampton et al.,⁴ Lim et al.,²² Macdougall et al.,²³ and Simons et al. ²⁴ [Color figure can be viewed at wileyonlinelibrary.com]