Anti-fibrotic therapy in Crohn’s disease: hype or reality—can intestinal fibrosis be targeted effectively?

INTRODUCTION: Fibrostenotic Crohn's disease remains a major unmet clinical need, as currently licensed therapies primarily target inflammation and have not been shown to prevent fibrosis progression or reverse established strictures. Renewed interest in intestinal fibrosis, coupled with an expanding therapeutic pipeline, has prompted renewed debate over whether anti-fibrotic therapy in Crohn's disease represents hype or a realistic therapeutic opportunity. AREAS COVERED: This special report summarizes emerging anti-fibrotic strategies in Crohn's disease, including clinical data for ontunisertib and preclinical evidence for anti-TL1A therapies and obefazimod. It also examines lessons from successful anti-fibrotic drug development in pulmonary and hepatic fibrosis, focusing on pathway selection, patient stratification, endpoint development, and trial design. EXPERT OPINION: Early clinical and translational findings suggest that targeting fibrosis in Crohn's disease may be feasible. In the authors' view, the greater challenge lies in developing the tools and trial frameworks needed to demonstrate that therapies can alter the course of fibrostenotic disease.