Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose-the randomized controlled HOMe aFers study

I E Emrich, F Lizzi, J D Siegel, S Seiler-Mussler, C Ukena, D Kaddu-Mulindwa, R D'Amelio, S Wagenpfeil, V M Brandenburg, M Böhm, D Fliser, G H Heine, I E Emrich, F Lizzi, J D Siegel, S Seiler-Mussler, C Ukena, D Kaddu-Mulindwa, R D'Amelio, S Wagenpfeil, V M Brandenburg, M Böhm, D Fliser, G H Heine

Abstract

Background: In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively.

Methods: In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias.

Results: Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 [75%]) than in those treated with FDI (1 out of 13 [8%]; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants.

Conclusions: While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI.

Trial registration: Clinical Trials.gov NCT02905539. Registered on 8 September 2016. 2015-004808-36 (EudraCT Number) U1111-1176-4563 (WHO Universal Trial Number) DRKS00010766 (Deutsches Register Klinischer Studien).

Keywords: FGF23; Ferric carboxymaltose; Ferric derisomaltose; Hypophosphatemia; Iron deficiency anemia.

Conflict of interest statement

Dr. Emrich received advisory board and speaker honoraria from Pharmacosmos. Dr. Heine and Dr. Brandenburg received advisory board and speaker honoraria from Pharmacosmos and from Vifor. Dr. Böhm is supported by the Deutsche Forschungsgemeinschaft (DFG, TTR 219, S-01, M-03, M-05) and reports support from Abbott, Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Medtronic, Novartis, ReCor, Servier, and Vifor. Dr. Wagenpfeil is supported by the Deutsche Forschungsgemeinschaft (DGF, TTR 219, PI: S-01) and reports support from Servier. Dr. Fliser is supported by the Deutsche Forschungsgemeinschaft (DGF, TTR 219) and reports support from Abbott, Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, FMC, Medtronic, Novartis, ReCor, Servier, and Vifor. Dr. Kaddu-Mulindwa reports support from Gilead, Janssen-Cilag, BMS, Takeda, Roche, Novartis, Hexal, and Viiv.

Fabio Lizzi, Jonathan Siegel, Sarah Seiler-Mußler, Christian Ukena, and Roberto D’Amelio have no conflict of interests.

Figures

Fig. 1
Fig. 1
Changes of parameters of bone and mineral metabolism in both treatment arms over time after intravenous iron repletion up to day 35 ± 2. Mean and standard deviation are given for every single time point (see whiskers in graphics)

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