Indirect methods of comparison of the safety of ferric derisomaltose, iron sucrose and ferric carboxymaltose in the treatment of iron deficiency anemia

ABSTRACT

Objectives: The benefits of intravenous (IV) iron greatly outweigh the risks, but IV iron formulations carry a small risk of hypersensitivity reactions (HSRs). The objective was to use standardized Medical Dictionary for Regulatory Activities queries (SMQs) to compare the safety of ferric derisomaltose/iron isomaltoside 1000 (FDI), iron sucrose (IS), and ferric carboxymaltose (FCM) using prospective trial data.

Methods: Prospective trials reporting the incidence of SMQ-coded serious or severe HSRs were identified in the literature. Four SMQs were used: narrow hypersensitivity terms (A), and broad terms pertaining to potential respiratory HSRs (B), skin HSRs (C), and cardiovascular HSRs (D). Bayesian inference, naïve pooling, and adjusted indirect approaches were employed to compare HSR incidence.

Results: Twenty one prospective trials including over 8,000 patients receiving FDI, FCM or IS were retrieved. Odds ratios of any serious or severe HSR (all groups) with FDI relative to FCM were 0.41, 0.39, and 0.45 according to the Bayesian, naïve and adjusted approaches, respectively.

Conclusions: The risk of serious or severe HSRs was lower with FDI relative to FCM and IS. Using data from prospective trials including over 8,000 patients coded using a well-defined standard (SMQs) enabled a robust comparison of HSR incidence between the iron formulations.

KEYWORDS:

• Iron
• Administration
• Intravenous
• Iron deficiency anemia
• Iron isomaltoside
• Ferric derisomaltose

Author contributions

RFP and PB devised the analysis plan. RFP ran the analyses, generated the tables and figures, and drafted the manuscript. PB reviewed the manuscript for intellectual content. RFP then prepared the final version of the manuscript, which was reviewed by both RFP and PB prior to submission.

Declaration of interest

RFP is the director of Covalence Research Ltd, which received consultancy fees from Pharmacosmos A/S to conduct the statistical analyses and prepare the manuscript. PB has received lecturing and consultant fees from Vifor-Fresenius Medical care, Medice, and Pharmacosmos A/S. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The analysis and manuscript preparation were funded by Pharmacosmos A/S, the marketing authorization holder for ferric derisomaltose/iron isomaltoside 1000.