Gut. 2023 Apr;72(4):644-653.doi: 10.1136/gutjnl-2022-327897. Epub 2022 Sep 9.

Heinz Zoller ¹, Myles Wolf ², Irina Blumenstein ³, Christian Primas ⁴, Stefan Lindgren ⁵, Lars L Thomsen ⁶, Walter Reinisch ⁷, Tariq Iqbal ⁸

Author information

¹Department of Medicine I and Christian Doppler Laboratory on Iron and Phosphate Biology, Medical University of Innsbruck, Innsbruck, Austria heinz.zoller@i-med.ac.at.

²Division of Nephrology, Department of Medicine, and Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.

³Medical Clinic I, Department of Gastroenterology, Hepatology, and Clinical Nutrition, University Clinic Frankfurt, Frankfurt, Germany.

⁴Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

⁵Department of Gastroenterology and Hepatology, Skåne University Hospital Malmö, Lund University, Lund, Sweden.

⁶Department of Clinical and Non-Clinical Research, Pharmacosmos A/S, Holbæk, Denmark.

⁷Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

⁸Department of Gastroenterology, Queen Elizabeth Hospital Birmingham, Birmingham, UK.

Abstract

Objective: Intravenous iron-a common treatment for anaemia and iron deficiency due to inflammatory bowel disease (IBD)-can cause hypophosphataemia. This trial compared the incidence of hypophosphataemia after treatment with ferric carboxymaltose (FCM) or ferric derisomaltose (FDI).

Design: This randomised, double-blind, clinical trial was conducted at 20 outpatient hospital clinics in Europe (Austria, Denmark, Germany, Sweden, UK). Adults with IBD and iron deficiency anaemia (IDA) were randomised 1:1 to receive FCM or FDI at baseline and at Day 35 using identical haemoglobin- and weight-based dosing regimens. The primary outcome was the incidence of hypophosphataemia (serum phosphate <2.0 mg/dL) at any time from baseline to Day 35 in the safety analysis set (all patients who received ≥1 dose of study drug). Markers of mineral and bone homeostasis, and patient-reported fatigue scores, were measured.

Results: A total of 156 patients were screened; 97 (49 FDI, 48 FCM) were included and treated. Incident hypophosphataemia occurred in 8.3% (4/48) FDI-treated patients and in 51.0% (25/49) FCM-treated patients (adjusted risk difference: -42.8% (95% CI -57.1% to -24.6%) p<0.0001). Both iron formulations corrected IDA. Patient-reported fatigue scores improved in both groups, but more slowly and to a lesser extent with FCM than FDI; slower improvement in fatigue was associated with greater decrease in phosphate concentration.

Conclusion: Despite comparably effective treatment of IDA, FCM caused a significantly higher rate of hypophosphataemia than FDI. Further studies are needed to address the longer-term clinical consequences of hypophosphataemia and to investigate mechanisms underpinning the differential effects of FCM and FDI on patient-reported fatigue.