Relative Incidence of Acute Adverse Events with Ferumoxytol Compared to Other Intravenous Iron Compounds: A Matched Cohort Study.

James B Wetmore,Eric D Weinhandl,Jincheng Zhou,David T Gilbertson,Abelardo I Aguilera

doi:10.1371/journal.pone.0171098

James B Wetmore, Eric D Weinhandl + Show 3 more

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https://doi.org/10.1371/journal.pone.0171098

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Abstract

Concerns persist about adverse reactions to intravenous (IV) iron. We aimed to determine the relative safety of ferumoxytol compared to other IV iron compounds. This retrospective cohort study with propensity-score matching for patients and drug doses used the Medicare 20% random sample to identify patients (1) without chronic kidney disease (non-CKD) and (2) with non-dialysis-dependent chronic kidney disease (NDD-CKD) who received a first dose of IV iron in 2010–2012. Exposures were ferumoxytol, iron sucrose, sodium ferric gluconate, or iron dextran. Outcomes were hypersensitivity symptoms, anaphylaxis, emergency department (ED) encounters, hospitalizations, and death after acute IV iron exposure. In the primary analysis for reactions on the day of or following exposure, there was no difference in hypersensitivity symptoms (hazard ratio 1.04, 95% confidence interval 0.94–1.16) or hypotension (0.83, 0.52–1.34) between 4289 non-CKD ferumoxytol users and an equal number of users of other compounds; results were similar for 7358 NDD-CKD patients and an equal number of controls. All-cause ED encounters or hospitalizations were less common in both the non-CKD (0.56, 0.45–0.70) and NDD-CKD ferumoxytol-treated patients (0.83, 0.71–0.95). Fewer than 10 deaths occurred in both the non-CKD and NDD-CKD ferumoxytol users and in matched controls; the hazard for death did not differ significantly between ferumoxytol users and controls in the non-CKD patients (2.00, 0.33–11.97) or in the NDD-CKD patients (0.25, 0.04–1.52). Multiple sensitivity analyses showed similar results. Ferumoxytol did not appear to be associated with more adverse reactions than other compounds for the treatment of iron-deficiency anemia in both non-CKD and NDD-CKD patients.

Highlights

Iron-deficiency anemia (IDA) is a common disorder in both the general and the chronic kidney disease (CKD) populations [1]
While subsequent work demonstrated that high-molecular-weight iron dextran formulations conferred the greater risk [18,20,30], a perception persisted that iron dextrans in general produced unacceptable rates of serious adverse events [27]
Despite clinical trials in patients without known multidrug allergies that suggested that ferumoxytol was no less safe than iron sucrose [25] and oral iron [31,32], reporting of spontaneous adverse events prompted the Food and Drug Administration (FDA) to attach a boxed warning to its label [33]

Summary

Introduction

Iron-deficiency anemia (IDA) is a common disorder in both the general and the chronic kidney disease (CKD) populations [1]. An early parenteral compound in the US was high-molecular-weight iron dextran (Imferon, Fisons), which was later withdrawn from the market, while low-molecular-weight iron (INFeD, Actavis Pharma) was introduced with a US Food and Drug Administration (FDA) boxed warning (colloquially, a “black box”) in the product label [29]. While subsequent work demonstrated that high-molecular-weight iron dextran formulations conferred the greater risk [18,20,30], a perception persisted that iron dextrans in general produced unacceptable rates of serious adverse events [27]. Despite clinical trials in patients without known multidrug allergies that suggested that ferumoxytol was no less safe than iron sucrose [25] and oral iron [31,32], reporting of spontaneous adverse events prompted the FDA to attach a boxed warning to its label [33]

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