1. In this randomized controlled trial, among patients with moderately to severely active ulcerative colitis, tulisokibart, a monoclonal antibody directed against TL1A, more effectively induced clinical remission compared with placebo.
2. Compared with placebo, the tulisokibart group consistently showed benefits in clinical response, endoscopic improvement, histologic improvement, symptomatic remission, and inflammatory biomarkers.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Ulcerative colitis is a chronic, inflammatory gastrointestinal disorder characterized by abdominal cramping, diarrhea, and rectal bleeding. While current therapy for moderately to severely active ulcerative colitis includes biologic and small-molecule therapies, no existing agents are associated with a high incidence of clinical remission among patients for whom conventional therapy has been ineffective. The present trial assessed the efficacy and safety of tulisokibart compared with placebo among patients with moderately to severely active ulcerative colitis. Compared with placebo, tulisokibart was more effective for induction of clinical remission, as well as clinical response, endoscopic improvement, histologic improvement, symptomatic remission, and reduction of biomarkers of inflammatory activity. Additionally, the safety and side-effect profile of tulisokibart were similar to those of placebo. A key limitation of the study was its inability to evaluate the therapeutic index of tulisokibart, with an assessment of more significant numbers of patients over more extended periods necessary for more precise efficacy and safety evaluations. Nevertheless, these findings provide valuable insights regarding a novel treatment option for patients with ulcerative colitis who have high baseline disease activity and are often refractory to treatment.
Click to read the study in NEJM
In-Depth [randomized controlled trial]: This phase 2 randomized-controlled trial compared the effects of tulisokibart with those of placebo on induction of clinical remission, clinical response, endoscopic improvement, histologic improvement, symptomatic remission, and levels of biomarkers of inflammatory activity. Patients 18 years of age or older with a diagnosis of moderately to severely active ulcerative colitis extending at least 15 cm from the anal verge were included. The primary outcome was clinical remission at week 12, defined as a modified Mayo endoscopic subscore of 0 or 1, a rectal-bleeding subscore of 0, and a stool-frequency subscore of 0 or 1. Out of 198 patients who underwent screening, 68 were assigned randomly to receive tulisokibart and 67 to receive a placebo. At week 12, the percentage of patients who achieved clinical remission in the tulisokibart group was 26% compared to 1% in the placebo group (95% Confidence Interval [CI], 14 to 37). Treatment differences for tulisokibart compared with placebo were 44 percentage points for achievement of clinical response (95% CI, 27 to 57), 31 percentage points for endoscopic improvement (95% CI, 17 to 43), 29 percentage points for histologic improvement (95% CI, 12 to 43), and 13 percentage points for symptomatic remission (95% CI, 2 to 25). Levels of biomarkers of inflammatory activity were also found to decrease more with tulisokibart than with placebo, with differences evident as early as week two for high-sensitivity C-reactive protein and week six for fecal calprotectin. The safety of tulisokibart was also assessed, and the safety and side-effect profile of tulisokibart was similar to those of placebo. In summary, among patients with moderately to severely active ulcerative colitis, tulisokibart was safe and more effective for induction of clinical remission.
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