TL1A Inhibition in Inflammatory Bowel Disease: A Pipeline Review.

Abstract

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), remains challenging to manage, with a substantial proportion of patients not responding to conventional therapies or developing complications. The tumor necrosis factor (TNF) superfamily member TL1A has emerged as an important player in the pathogenesis of IBD, influencing pathways of inflammation and fibrosis. This leading article reviews the role of TL1A in IBD, evaluates the efficacy of anti-TL1A therapies in clinical trials, and discusses future directions for research and treatment. TL1A is implicated in IBD through its interaction with death domain receptor 3 (DR3), promoting T-cell activation and contributing to both inflammatory responses and fibrotic changes. Phase 2 clinical trials of anti-TL1A agents have demonstrated promising results, showing improvements in endoscopic and histologic outcomes for both UC and CD. Phase 2 and 3 clinical trials are ongoing, which are expected to provide further clarity on the efficacy and safety of TL1A-targeting agents in treating IBD.