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

  • Aliment Pharmacol Ther. 2026 Jun;63(11):1458-1473. doi: 10.1111/apt.70648.
Manjeet Kumar Goyal  1 ,  Harsh Srivastava  2 ,  Tanisha Sehgal  3 ,  Shrinivas Bishu  4 ,  Vishal Sharma  5 ,  Shaji Sebastian  6
Affiliations
  • 1. Department of Internal Medicine, Cleveland Clinic Akron General, Akron, Ohio, USA.
  • 2. Department of Medicine, VMMC and Safdarjung Hospital, New Delhi, India.
  • 3. Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, India.
  • 4. Clinical Assistant Professor, Division of Gastroenterology, Department of Medicine, Michigan Medicine, Ann Arbor, Michigan, USA.
  • 5. Additional Professor of Gastroenterology, Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
  • 6. IBD Unit, Department of Gastroenterology, Hull University Teaching Hospitals NHS Trust, Hull, UK.
PMID: 41941212 DOI: 10.1111/apt.70648
Abstract

Background: 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).

Aims: 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.

Methods: Narrative synthesis of preclinical, translational, and clinical literature on TL1A/DR3 in Crohn's Disease and Ulcerative Colitis.

Results: 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.

Conclusion: 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.

Keywords
TL1A; afimkibart; crohn's disease; duvakitug; inflammatory bowel diseases; tulisokibart; tumour necrosis factor‐like ligand 1A; ulcerative colitis.
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