Inflamm Bowel Dis. 2021 May 14;izab073. doi: 10.1093/ibd/izab073. Online ahead of print.

Stefanie Howaldt ¹, Eugeni Domènech ², Nicholas Martinez ³, Carsten Schmidt ⁴, Bernd Bokemeyer ⁵

Author information

• ¹Research Institute for IBD-HaFCED e.K., Hamburg, Germany.
• ²Gastroenterology and Hepatology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Madrid, Spain.
• ³Gastroenterology Research of America, San Antonio, Texas, USA.
• ⁴Department of Gastroenterology, Hepatology, Endocrinology, Diabetology, and Infectious Diseases, Klinikum Fulda, Fulda, Germany.
• ⁵Gastroenterology Practice Minden and University Hospital Schleswig-Holstein, Campus Kiel, Clinic for Internal Medicine I, Kiel, Germany.

Abstract

Background: Iron-deficiency anemia is common in inflammatory bowel disease, requiring oral or intravenous iron replacement therapy. Treatment with standard oral irons is limited by poor absorption and gastrointestinal toxicity. Ferric maltol is an oral iron designed for improved absorption and tolerability.

Methods: In this open-label, phase 3b trial (EudraCT 2015-002496-26 and NCT02680756), adults with nonseverely active inflammatory bowel disease and iron-deficiency anemia (hemoglobin, 8.0-11.0/12.0 g/dL [women/men]; ferritin, <30 ng/mL/<100 ng/mL with transferrin saturation <20%) were randomized to oral ferric maltol 30 mg twice daily or intravenous ferric carboxymaltose given according to each center's standard practice. The primary endpoint was a hemoglobin responder rate (≥2 g/dL increase or normalization) at week 12, with a 20% noninferiority limit in the intent-to-treat and per-protocol populations.

Results: For the intent-to-treat (ferric maltol, n = 125/ferric carboxymaltose, n = 125) and per-protocol (n = 78/88) analyses, week 12 responder rates were 67% and 68%, respectively, for ferric maltol vs 84% and 85%, respectively, for ferric carboxymaltose. As the confidence intervals crossed the noninferiority margin, the primary endpoint was not met. Mean hemoglobin increases at weeks 12, 24, and 52 were 2.5 vs 3.0 g/dL, 2.9 vs 2.8 g/dL, and 2.7 vs 2.8 g/dL with ferric maltol vs ferric carboxymaltose. Treatment-emergent adverse events occurred in 59% and 36% of patients, respectively, and resulted in treatment discontinuation in 10% and 3% of patients, respectively.

Conclusions: Ferric maltol achieved clinically relevant increases in hemoglobin but did not show noninferiority vs ferric carboxymaltose at week 12. Both treatments had comparable long-term effectiveness for hemoglobin and ferritin over 52 weeks and were well tolerated.