Review Article: TL1A Inhibitors in IBD - Mechanistic Rationale and Clinical Evidence

Tumour necrosis factor-like ligand 1A (TL1A) and its receptor DR3 form a pivotal signalling dyad linking immune activation, epithelial barrier dysfunction and fibrogenesis in inflammatory bowel diseases. (IBD).

This narrative review summarizes the molecular biology of the TL1A-DR3 axis, its roles in intestinal inflammation, fibrosis, and extraintestinal manifestations, and the emerging therapeutic landscape of TL1A inhibition in IBD.

Narrative synthesis of preclinical, translational, and clinical literature on TL1A/DR3 in Crohn's disease and ulcerative colitis.

TL1A overexpression drives Crohn's-like ileitis, barrier disruption, and fibrosis in models; blockade attenuates both inflammation and remodelling. TL1A inhibitors show clinical/endoscopic remission in early-phase moderate-severe IBD trials (e.g., tulisokibart, duvakitug), with phase 3 programs ongoing.

TL1A-DR3 integrates mucosal immunity with stromal injury, positioning inhibitors as a novel class to overcome IBD therapeutic ceilings by targeting the inflammation-fibrosis continuum.