The Safety and Efficacy of Ferumoxytol in the Treatment of Iron Deficiency: A Systematic Review and Meta-Analysis

Abstract

BackgroundIron deficiency (ID) is one of the most common nutritional deficiencies worldwide, with an increased prevalence in pathological states such as end stage renal disease and inflammatory bowel disorders. Iron stores can be replenished by either oral or intravenous (IV) formulations, however IV formulations are known to raise iron stores more quickly and reliably. Ferumoxytol is an IV iron formulation used in the treatment of ID that, advantageously, can be given in large doses over a short period of time. Despite the initial large quantity of post-marketing reports of serious adverse events (SAEs), multiple clinical trials have failed to demonstrate a significant safety signal.ObjectivesTo determine the safety and efficacy of ferumoxytol in the treatment of ID compared to other IV and oral iron formulations, and placebo.MethodsThis systematic review and meta-analysis was conducted following the Cochrane Handbook, and was reported as per Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.We searched the Cochrane Library, Medline, and EMBASE from inception until February 2018 as well as trial registries and reference lists of relevant articles.All randomized or quasi-randomized controlled trials comparing ferumoxytol to alternate IV iron, oral iron, or placebo were included. Outcomes included treatment emergent adverse events (TEAEs), treatment related adverse events (TRAEs), SAEs, related serious adverse events (RSAEs), hypotension or hypersensitivity reactions (HHR) and composite cardiovascular outcomes (CCO).Two review authors independently extracted data and assessed included studies for risk of bias. If required, additional data was sought from trial authors. Meta-analysis was performed using the Review Manager 5.3. Data was pooled using random-effects models. Risk of bias was assessed using the Cochrane Collaboration tool Risk of Bias. The GRADE approach was used to assess quality of evidence.ResultsThe review included nine studies, one of which was a cross-over trial. These included 5691 participants (mean age 54.3, study mean range 30 to 65.1 years). Ferumoxytol was compared to alternate IV iron in three studies, to oral iron in two, and to placebo in four. Overall, studies were at low risk of bias (see figure 1).There was high quality evidence that relative to other IV iron formulations, ferumoxytol has little to no increase in the achievement of a minimum 1g/dL increase in hemoglobin (Relative Risk [RR] 1.04, 95%Confidence Interval [CI] 0.96 to 1.12; 767 participants pooled (pp) from 2 trials)), low quality evidence that it has little to no decrease in TEAE (RR 0.88, 95%CI 0.80 to 0.97; 2764 pp from 3 trials), little to no decrease in TRAEs (RR 0.73, 95%CI 0.61 to 0.88; 2764 pp from 3 trials), little to no increase on SAEs (RR 1.13, 95%CI 0.77 to 1.67; 2764 pp from 3 trials), and little to no decrease in RSAEs (RR 0.58, 95%CI 0.13 to 2.55; 2764 pp from 3 trials), very low quality evidence that it has little to no decrease in HHR (RR 0.58, 95%CI 0.31 to 1.09; 2764 pp from 3 trials) and moderate quality evidence that it has little to no decrease on CCO (RR 0.56, 95% CI 0.24 to 1.29; 2602 pp from 2 trials).Compared to oral iron, ferumoxytol had less TEAEs (RR 0.78, 95%CI 0.61 to 0.98; 515 pp from 2 trials), but compared to placebo ferumoxytol had more (RR 1.62, 95%CI 1.01 to 2.61; 2348 pp from 3 trials).Publication bias was not assessed due to the limited number of studies included.ConclusionsUpon review of the available evidence, ferumoxytol is probably as efficacious as alternative IV iron formulations with no clear safety concerns. In addition, ferumoxytol had less TEAEs compared to oral iron formulations, but more compared to placebo. DisclosuresAuerbach:AMAG Pharmaceuticals: Research Funding; Pharmacosmos A/S: Research Funding.