Clinical Trial: Predicting Response to Iron Therapy in Patients With Active Inflammatory Bowel Disease Using Hepcidin and Functional Iron Indices: A Multicentre Randomised Trial

ABSTRACT Background Iron deficiency anaemia (IDA) is common in inflammatory bowel disease (IBD) and impairs quality of life. Hepcidin, the regulator of systemic iron homeostasis, may predict response to iron therapy; however, its utility in IBD remains unclear. This study evaluated whether baseline hepcidin predicts response to oral and intravenous (IV) iron in active IBD to guide personalised treatment. Methods Ninety adults with active IBD and iron deficiency (with or without anaemia) from two randomised trials received IV iron, oral ferrous fumarate (FF) or oral ferric maltol (FM). Response at 12 weeks was defined as haemoglobin increase ≥ 1.2 mmol/L (19.3 g/L) or normalisation in IDA or ferritin > 100 μg/L and transferrin saturation > 20% in iron deficient patients. Baseline iron indices including ferritin, hepcidin, and soluble transferrin receptor (sTfR) were measured. Logistic regression and receiver operating curve analyses evaluated predictive performance. Results Baseline hepcidin strongly predicted response to iron therapy: AUC (FF) : 0.86, 95% CI: 0.71–1.00 and AUC (IV) : 0.63, 95% CI: 0.30–0.96. Hepcidin > 2.68 μg/mL identified non‐responders to FF with 89% sensitivity and 77% specificity. Each twofold increase in baseline hepcidin or ferritin reduced the odds of response [log 2 (hepcidin) OR: 0.71, 95% CI: 0.56–0.89; log 2 (ferritin) OR: 0.38, 95% CI: 0.21–0.69]. Higher transferrin/log 10 (ferritin) (OR: 2.95, 95% CI: 1.38–6.30) and sTfR/log 10 (ferritin) ratios (OR: 1.29, 95% CI: 1.05–1.59) increased likelihood of response. Conclusion Baseline hepcidin supports route selection for iron therapy: higher levels favour IV iron, while lower levels indicate likely oral response. Ferritin‐based indices, notably transferrin/log 10 (ferritin), offer pragmatic alternatives where hepcidin testing is unavailable. Trial Registration ClinicalTrials.gov identifier: NCT05581420 and NCT05456932