TOPLINE

Among patients with active inflammatory bowel disease (IBD), higher baseline hepcidin levels predicted poorer response to iron therapy, particularly after oral iron treatment. Ferritin-based indices, especially the transferrin/log₁₀ (ferritin) ratio, also showed strong predictive performance, providing a practical alternative in the absence of hepcidin measurement.

METHODOLOGY

• Hepcidin, the regulator of systemic iron homeostasis, may help guide iron therapy in IBD by limiting ferroportin-mediated iron absorption and mobilization; hepcidin levels rise during inflammation or iron excess, while they fall in iron deficiency.
• Researchers pooled data from two open-label randomized controlled trials conducted across multiple hospitals in Netherlands, involving 90 adults (median age, 40 years; 58.9% women) with active IBD and iron deficiency with or without anemia.
• Participants received intravenous (IV) iron (n = 39), oral ferrous fumarate (n = 38), or oral ferric maltol (n = 13); IV iron was dosed on the basis of hemoglobin level and body weight, ferric maltol was administered at a dose of 30 mg twice daily for 12 weeks, and ferrous fumarate was administered as 200 mg daily, with dose adjustment after hemoglobin normalization in some patients.
• The primary outcome was the predictive value of baseline hepcidin levels for treatment response to iron therapy at 12 weeks.
• Treatment response was defined as a hemoglobin increase of at least 1.2 mmol/L or hemoglobin normalization in patients with iron deficiency anemia and as ferritin levels of more than 100 μg/L plus transferrin saturation above 20% in patients with iron deficiency.

TAKEAWAY

• At week 12, 60.9% of patients responded to iron therapy overall, with higher response rates observed with IV iron (84.4%) than with oral ferrous fumarate and ferric maltol (37.5% each).
• Each twofold increase in ferritin (odds ratio [OR], 0.38; P = .002) or hepcidin (OR, 0.71; P = .003) was associated with a lower likelihood of response to iron therapy. In contrast, higher transferrin/log₁₀ (ferritin) and soluble transferrin receptor/log₁₀ (ferritin) ratios were associated with increased odds of response (OR, 2.95; P = .005 and OR, 1.29; P = .015, respectively).
• Baseline hepcidin demonstrated good discriminative ability for predicting response to iron therapy overall, with an area under the curve (AUC) of 0.76; it performed particularly well in the ferrous fumarate group (AUC, 0.86), with more limited discrimination in the IV iron group (AUC, 0.63).
• A hepcidin level above 9.2 μg/mL was associated with nonresponse (sensitivity, 83%; specificity, 65%), while a lower cutoff (> 2.68 μg/mL) identified likely nonresponders to oral ferrous fumarate (sensitivity, 89%; specificity, 77%). This suggests that patients with active IBD and mild iron deficiency or mild anemia may benefit more from IV iron than from oral iron.

IN PRACTICE

“Baseline hepcidin can identify patients less likely to respond to iron, particularly oral therapy, while ferritin-based indices, such as the transferrin/log₁₀ (ferritin) ratio, offer practical alternatives. These findings support a personalized approach to iron supplementation in IBD,” the authors of the study wrote.

SOURCE

The study was led by Lola J.M. Koppelman, Leiden University Medical Center, Leiden, Netherlands. It was published online in Alimentary Pharmacology & Therapeutics.

LIMITATIONS

Data were pooled from two trials with differences in ferrous fumarate dosing, which may have influenced treatment response. Also, poor adherence to oral iron may have contributed to reduced treatment response.

DISCLOSURES

One of the trials included in this study was funded by ZonMw, the Netherlands Organisation for Health Research and Development, and the other trial was partially funded by Norgine Ltd. Some authors declared receiving travel expenses, speaker’s fees, advisory board honoraria, and unrestricted grants and having served on advisory boards for various pharmaceutical and biotech companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.