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Meta-Analysis
. 2023 Jun;45(3):604-612.
doi: 10.1007/s11096-023-01548-2. Epub 2023 Apr 3.

A systematic literature review and meta-analysis of the incidence of serious or severe hypersensitivity reactions after administration of ferric derisomaltose or ferric carboxymaltose

Nicholas A Kennedy  1 , Maureen M Achebe  2 , Patrick Biggar  3 , Johannes Pöhlmann  4 , Richard F Pollock  5
Affiliations
Meta-Analysis

A systematic literature review and meta-analysis of the incidence of serious or severe hypersensitivity reactions after administration of ferric derisomaltose or ferric carboxymaltose

Nicholas A Kennedy et al. Int J Clin Pharm. 2023 Jun.

Abstract

Background: Intravenous iron is the preferred treatment for patients with iron deficiency anemia in a variety of clinical situations. Although uncommon, administration of modern IV iron formulations can result in hypersensitivity reactions (HSRs) and, rarely, anaphylactic or anaphylactoid reactions.

Aim: The objective of the present study was to systematically review the literature to identify and analyze data on the incidence of HSRs after administration of ferric derisomaltose (FDI) or ferric carboxymaltose (FCM).

Method: A prospectively-registered systematic literature review was conducted to identify prospective randomized controlled trials comparing FDI and FCM with other intravenous iron formulations or oral iron. Searches were conducted in PubMed (including MEDLINE), EMBASE, and the Cochrane Library in November 2020. The relative incidence of serious or severe HSRs occurring on the day or day after dosing of intravenous iron, recorded under the standardized Medical Dictionary for Regulatory Activities query for anaphylactic reaction.

Results: Data were obtained from seven randomized controlled trials of FCM (N = 2683) and ten of FDI (N = 3474) enrolling 10,467 patients in total. The number of patients experiencing any serious or severe HSR event was 29/2683 (1.08%) with FCM versus 5/3474 with FDI (0.14%). Bayesian inference of proportions showed the event rates to be significantly lower with FDI relative to FCM.

Conclusion: HSR events were uncommon with both intravenous iron formulations; however, the present study showed a significantly lower incidence of HSRs with FDI relative to FCM. Further large-scale, head-to-head trials of the iron formulations would be required to confirm this finding.

Keywords: Administration, intravenous; Ferric carboxymaltose; Ferric derisomaltose; Hypersensitivity; Iron; Iron deficiency anemia; Iron isomaltoside.

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Conflict of interest statement

JP is a full-time employee, and RFP is a shareholder, director, and full-time employee of Covalence Research Ltd, which has received consultancy fees from Pharmacosmos A/S to perform the systematic literature review, conduct the pooled analysis, and draft the manuscript. MA has no conflicts of interest to declare. PB declares consultancy fees from Vifor, Fresenius, and Pharmacosmos A/S. NK declares speaker honoraria, support for meetings and/or travel, and participation in an advisory board from Pharmacosmos A/S.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram showing the two searches to identify randomized controlled trials comparing ferric derisomaltose and ferric carboxymaltose with any other intravenous or oral iron formulation
Fig. 2
Fig. 2
Flow diagram for data requests and incorporation of publicly available data
Fig. 3
Fig. 3
Posterior distributions from the Bayesian inference of proportions of the odds of serious or severe hypersensitivity reactions occurring on the day or day after administration of intravenous iron for FDI versus FCM. Green dotted line indicates parity (odds ratio of 1); red dashed lines indicate the region of practical equivalence (ROPE). A Narrow terms pertaining to hypersensitivity reactions, B broad terms pertaining to respiratory reactions potentially related to hypersensitivity, C broad terms pertaining to skin reactions potentially related to hypersensitivity, D broad terms pertaining to cardiovascular reactions potentially related to hypersensitivity, FCM ferric carboxymaltose, FDI ferric derisomaltose, HDI highest posterior density interval, ROPE region of practical equivalence
Fig. 4
Fig. 4
Naïve pooled analysis of the safety of ferric derisomaltose (FDI) versus ferric carboxymaltose (FCM) with odds ratios and confidence intervals of serious or severe hypersensitivity reactions occurring on the day or day after administration of intravenous iron for FDI versus FCM derived using the Clopper Pearson method, and p values derived using the Fishers exact test. A Narrow terms pertaining to hypersensitivity reactions, B broad terms pertaining to respiratory reactions potentially related to hypersensitivity, C broad terms pertaining to skin reactions potentially related to hypersensitivity, D broad terms pertaining to cardiovascular reactions potentially related to hypersensitivity, FCM ferric carboxymaltose, FDI ferric derisomaltose, MedDRA Medical Dictionary for Regulatory Activities, OR odds ratio
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