TL1A inhibition for inflammatory bowel disease treatment: From inflammation to fibrosis

Virginia Solitano; Vipul Jairath; Federica Ungaro; Laurent Peyrin-Biroulet; Silvio Danese

doi:10.1016/j.medj.2024.03.010

TL1A inhibition for inflammatory bowel disease treatment: From inflammation to fibrosis

Med. 2024 May 10;5(5):386-400. doi: 10.1016/j.medj.2024.03.010. Epub 2024 Apr 3.

Authors

Virginia Solitano¹, Vipul Jairath², Federica Ungaro³, Laurent Peyrin-Biroulet⁴, Silvio Danese⁵

Affiliations

¹ Division of Gastroenterology, Western University, London, ON, Canada; Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy.
² Division of Gastroenterology, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
³ Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy; Division of Immunology, Transplantation, and Infectious Disease, IRCCS Ospedale San Raffaele, Milan, Italy.
⁴ Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France; Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France; INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France; FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy, France; Groupe Hospitalier privé Ambroise Paré - Hartmann, Paris IBD Center, Neuilly sur Seine, France; Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada.
⁵ Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy. Electronic address: sdanese@hotmail.com.

PMID: 38574740
DOI: 10.1016/j.medj.2024.03.010

Abstract

The pivotal role of TL1A in modulating immune pathways crucial for inflammatory bowel disease (IBD) and intestinal fibrosis offers a promising therapeutic target. Phase 2 trials (TUSCANY and ARTEMIS-UC) evaluating an anti-TL1A antibody show progress in expanding IBD therapeutic options. First-in-human data reveal reduced expression of genes associated with extracellular matrix remodeling and fibrosis post-anti-TL1A treatment. Investigational drug TEV-48574, potentially exerting dual antifibrotic and anti-inflammatory effects, is undergoing a phase 2 basket study in both ulcerative colitis (UC) and Crohn disease (CD). Results are eagerly awaited, marking advancements in IBD therapeutics. This critical review comprehensively examines the existing literature, illuminating TL1A and the intricate role of DR3 in IBD, emphasizing the evolving therapeutic landscape and ongoing clinical trials, with potential implications for more effective IBD management.

Trial registration: ClinicalTrials.gov NCT05668013.

Keywords: DR3; PF-06480605; PRA023; TEV-48574; TL1A; TNF/TNFR superfamily; biomarker; chronic immunological diseases; gut inflammation; intestinal fibrosis; mucosal homeostasis.

Publication types

Review

MeSH terms

Anti-Inflammatory Agents / pharmacology
Anti-Inflammatory Agents / therapeutic use
Colitis, Ulcerative / drug therapy
Colitis, Ulcerative / immunology
Colitis, Ulcerative / pathology
Crohn Disease / drug therapy
Crohn Disease / immunology
Crohn Disease / pathology
Fibrosis* / drug therapy
Humans
Inflammation / drug therapy
Inflammation / immunology
Inflammatory Bowel Diseases* / drug therapy
Inflammatory Bowel Diseases* / immunology
Inflammatory Bowel Diseases* / pathology
Tumor Necrosis Factor Ligand Superfamily Member 15* / antagonists & inhibitors
Tumor Necrosis Factor Ligand Superfamily Member 15* / genetics
Tumor Necrosis Factor Ligand Superfamily Member 15* / metabolism

Substances

Tumor Necrosis Factor Ligand Superfamily Member 15
TNFSF15 protein, human
Anti-Inflammatory Agents

Associated data

ClinicalTrials.gov/NCT05668013