ARTEMIS-UC Phase II Trial: Tulisokibart (Anti-TL1A) Achieves Clinical Remission in Moderate to Severe Ulcerative Colitis
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A Phase II multicenter trial published in The New England Journal of Medicine found that tulisokibart, a novel monoclonal antibody targeting TL1A, safely achieved clinical remission in patients with moderate to severely active ulcerative colitis who had not responded adequately to prior therapies. Developed at Cedars-Sinai Medical Center, tulisokibart works by blocking TL1A, a protein that drives both inflammation and fibrosis in inflammatory bowel disease. The trial also introduced a companion genetic test that may one day help doctors predict which patients are most likely to respond to the therapy.
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting as many as 900,000 people in the United States, characterized by colonic inflammation, rectal bleeding, and cramping diarrhea. Many patients do not respond adequately to currently available therapies, including biologics and JAK inhibitors, highlighting the need for new treatment targets. Tumor necrosis factor-like cytokine 1A (TL1A), encoded by the TNFSF15 gene, acts as a master regulator of intestinal inflammation and fibrosis; elevated TL1A expression has been associated with increased IBD severity and worse mucosal outcomes. Tulisokibart (previously PRA023) is a humanized monoclonal antibody designed to block TL1A, reducing both inflammatory and fibrotic disease components.
ARTEMIS-UC was a 12-week, randomized, double-blind, placebo-controlled Phase II trial enrolling 178 adults with moderately to severely active UC across 14 countries. Participants had active disease despite prior conventional therapy and were stratified by TL1A genetic risk status using an investigational companion diagnostic test. Primary endpoints included clinical remission and endoscopic improvement at week 12. Patient-reported outcomes and fecal biomarkers were assessed throughout the trial.
Tulisokibart significantly outperformed placebo on both the primary clinical remission and endoscopic improvement endpoints. The drug was well tolerated, with a safety profile comparable to placebo. Patients identified as genetic responders via the companion diagnostic demonstrated particularly strong outcomes, providing the first clinical evidence that a precision medicine approach may be feasible in IBD treatment selection. The authors concluded that TL1A is a clinically meaningful target in UC and that tulisokibart warrants further investigation in a Phase III program.