Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial

Abstract

Few trials have examined rates of hypersensitivity reactions (HSRs) with intravenous iron formulations used to treat iron deficiency anemia (IDA). This randomized, multicenter, double‐blind clinical trial compared the safety, and efficacy of ferumoxytol versus ferric carboxymaltose (FCM), focusing on rates of HSRs and hypotension as the primary end point. Patients with IDA of any etiology in whom oral iron was unsatisfactory or intolerable received ferumoxytol (n = 997) or FCM (n = 1000) intravenously over ≥15 minutes on days 1 and 8 or 9 for total respective doses of 1.02 g and 1.50 g. Composite incidences of moderate‐to‐severe HSRs, including anaphylaxis, or moderate‐to‐severe hypotension from baseline to week 5 (primary safety end point) were 0.6% and 0.7% in the ferumoxytol and FCM groups, respectively, with ferumoxytol noninferior to FCM. No anaphylaxis was reported in either group. The secondary safety end point of incidences of moderate‐to‐severe HSRs, including anaphylaxis, serious cardiovascular events, and death from baseline to week 5 were 1.3% and 2.0% in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Least‐squares mean changes in hemoglobin at week 5 were 1.4 g/dL and 1.6 g/dL in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Incidence of hypophosphatemia was 0.4% for ferumoxytol and 38.7% for FCM.

The safety and efficacy of ferumoxytol in the treatment of iron deficiency: a systematic review and meta‐analysis

“…In addition, in a large retrospective cohort, the death rate per 100,000 of ferumoxytol was similar to the rates of other IV iron formulations including iron sucrose and iron gluconate . Since the last review published in 2015, many new trials have assessed the safety of ferumoxytol in various clinical settings . Therefore, given the benefits of ferumoxytol, coupled with its reports of potential safety concerns, it is important to reassess the evidence in this regard.…”

“…The nine included studies involved 5691 individuals. Three studies assessed ferumoxytol compared to alternate IV iron (iron sucrose in both Hetzel 2014 28 and Macdougall 2014, and ferric carboxymaltose in Adkinson 2018), two studies assessed ferumoxytol compared to oral iron (ferrous fumarate in both Spinowitz 2008 and Provenzano 2009), and four studies assessed ferumoxytol compared to placebo (Landry 2005, Singh 2008, Pai 2010, and Vadhan‐Raj 2014). See supplementary material, Table S3 and Table S4 for study characteristics.…”

The role of iron repletion in adult iron deficiency anemia and other diseases

“…In patients with NDD‐CKD, IV iron has been shown to rapidly correct anemia and reduce need for ESAs relative to oral iron without evidence of renal toxicity, cardiovascular, or infectious events . Rates of acute infusion‐related hypersensitivity reactions are low with IV iron use in NDD‐ and PD‐CKD patients and the safety of short‐term IV iron is established by multiple trials . A trial of oral iron may however be considered in NDD‐CKD patients based on the severity of their anemia, previous response to oral iron, venous access, and cost considerations .…”

“…66 Rates of acute infusion-related hypersensitivity reactions are low with IV iron use in NDD-and PD-CKD patients and the safety of short-term IV iron is established by multiple trials. [67][68][69] A trial of oral iron may however be considered in NDD-CKD patients based on the severity of their anemia, previous response to oral iron, venous access, and cost considerations. 61 Use of ESAs increases utilization of iron stores for hematopoiesis; they should only be used after functional or absolute iron deficiency has been corrected.…”

Data from a terminated study on iron oxide nanoparticle magnetic resonance imaging for head and neck tumors

“…Notably, however, in the interval since closing the trial, a randomized safety assessment for the FDA approved indication showed less than 1% incidence of moderate-to-severe toxicities (including anaphylaxis, or moderateto-severe hypotension) within 5 weeks of ferumoxytol administration 12 ; an update of 217 consecutive patients with wide range of ages, comorbid conditions and kidney functions given ferumoxytol specifically for MRI applications with no observed adverse events 13 ; and a report of 69 patients receiving 85 ferumoxytol injections for MRI with 4 reported mild adverse events (2 episodes mild hypotension and one episode of nausea, and one episode warmness/erythema at the in injection site) 14 .…”