Comparative Risk of Hypophosphatemia Following the Administration of Intravenous Iron Formulations: A Network Meta-Analysis

Intravenous iron therapy is increasingly used in patients with iron deficiency anemia, although concerns of hypophosphatemia have been recently raised. The aim of this study was to evaluate different intravenous iron formulations for the risk of hypophosphatemia. Medline, Scopus, Cochrane Central Register of Controlled Trials, Web of Science, Clinicaltrials.gov, and Google Scholar databases were systematically searched to 20 March 2020. All randomized controlled trials reporting the incidence of hypophosphatemia among adult patients treated with any intravenous iron preparation were included. Pool estimates were obtained by applying an arm-based Bayesian network meta-analysis model. Eight randomized controlled trials were included, comprising 5989 patients. Ferric carboxymaltose was associated with significantly higher incidence of hypophosphatemia compared to iron isomaltoside (risk ratio [RR]: 7.90, 95% confidence interval [CI]: 2.10-28.0), iron sucrose (RR: 9.40.95% CI: 230-33.0), iron dextran (RR: 6.60, 95%CI: 1.91-220.0), and ferumoxytol (RR: 24.0,95% CI: 2.50-220.0). Therefore. ferric carboxymaltose ranked as the worst treatment presenting the highest surface under the cumulative ranking curve (99.1%). No significant differences were estimated for the comparisons among iron isomaltoside, iron sucrose, iron dextran, and ferumoxytol. In condusion, it is suggested that the occurrence of hypophosphatemia is common after the administration of intravenous ferric carboxymaltose. Further research is needed in largescale randomized controlled trials to determine the risk of symptomatic and persistent hypophosphatemia as well as to elucidate the exact pathophysiology of the observed association. (C) 2020 Elsevier Inc. All rights reserved.