Ferumoxytol versus iron sucrose treatment: a post-hoc analysis of randomized controlled trials in patients with varying renal function and iron deficiency anemia

Abstract

Background: Iron deficiency anemia is highly prevalent in patients with chronic kidney disease and is often treated with intravenous iron. There are few trials directly comparing the safety and efficacy of different intravenous iron products.

Methods: This post-hoc analysis pooled data from 767 patients enrolled in two randomized, controlled, open-label trials of similar design comparing the treatment of iron deficiency anemia with ferumoxytol and iron sucrose across patients with all stages of renal function. One trial was conducted in adults with CKD either on or not on dialysis and the second in adults with IDA of any underlying cause and a history of unsatisfactory oral iron therapy or in whom oral iron could not be used who had normal to no worse than moderately impaired renal function. Patients were categorized by chronic kidney disease stage (i.e., estimated glomerular filtration rate), and the primary efficacy endpoint was the mean change in hemoglobin from Baseline to Week 5.

Results: The overall incidence of adverse events was numerically lower in ferumoxytol-treated patients compared to those treated with iron sucrose (42.4 vs. 50.2 %, respectively); the incidence of treatment-related adverse events was generally similar between the two treatment groups (13.6 vs. 16.0 %, respectively). Adverse events of Special Interest (i.e., hypotension, hypersensitivity) occurred at lower rates in those treated with ferumoxytol compared to those treated with iron sucrose (2.5 vs. 5.3 %, respectively). Overall, mean hemoglobin increased in both treatment groups, regardless of degree of renal insufficiency, although greater increases were seen among those with less severe kidney damage. Mean increases in hemoglobin from Baseline to Week 5 were significantly greater with ferumoxytol than with iron sucrose treatment in the subgroup with an estimated glomerular filtration rate ≥90 mL/min (Least Squares mean difference = 0.53 g/dL; p < 0.001). There were no other consistent, significant differences in hemoglobin levels between treatment groups for the other chronic kidney disease categories except for isolated instances favoring ferumoxytol.

Conclusions: The efficacy and safety of ferumoxytol is at least comparable to iron sucrose in patients with varying degrees of renal function.

Trial registration: (CKD-201; ClinicalTrials.gov identifier: NCT01052779; registered 15 January, 2010), (IDA-302; ClinicalTrials.gov identifier: NCT01114204; registered 29 April, 2010).

Keywords: Chronic kidney disease; Ferumoxytol; Hemoglobin; Iron deficiency anemia; Iron sucrose.

Figures

Fig. 1

Patient flow diagram. AE, adverse event

Fig. 2

Adverse events (AEs) within 24 h post-dosing. a All treatment-emergent AEs by treatment and dose number. b All treatment-related AEs by treatment and dose number. Pts, patients

Fig. 3

Mean hemoglobin (Hgb) levels across renal functions. a eGFR ≥90 mL/min; (b) eGFR 60 to <90 mL/min; (c) eGFR 30 to <60 mL/min; (d) eGFR 15 to <30 mL/min; and (e) eGFR <15 mL/min at Weeks 2, 3, 4, and 5 in patients receiving ferumoxytol or iron sucrose therapy (Intent-to-Treat population). eGFR, estimated glomerular filtration rate