Article Impact Level: HIGH Data Quality: STRONG Summary of New England Journal of Medicine, 391(12), 1119–1129. https://doi.org/10.1056/NEJMoa2314076 Dr. Bruce E. Sands et al.
Points
- This study evaluated tulisokibart, a monoclonal antibody targeting TL1A, for treating moderately to severely active ulcerative colitis. It used a genetic-based diagnostic test to identify likely responders.
- In Cohort 1, 26% of patients receiving tulisokibart achieved clinical remission at week 12, compared to 1% in the placebo group (P<0.001).
- In Cohort 2, which included only patients who tested positive for the likelihood of response, 32% of tulisokibart patients achieved remission versus 11% in the placebo group (P=0.02).
- Adverse events were similar between the tulisokibart and placebo groups, with most classified as mild to moderate.
- The study concluded that tulisokibart significantly improved clinical remission rates, especially in patients with a genetic likelihood of response, indicating its potential as a treatment option for ulcerative colitis.
Summary
This study evaluated the efficacy of tulisokibart, a monoclonal antibody targeting tumor necrosis factor-like cytokine 1A (TL1A), for treating moderately to severely active ulcerative colitis. A genetic-based diagnostic test was used to identify patients with a higher likelihood of response. Patients who were dependent on glucocorticoids or had failed conventional or advanced therapies were randomly assigned to receive either intravenous tulisokibart or placebo. In Cohort 1, which included all patients regardless of test results, the primary outcome was clinical remission at week 12. Cohort 2 included only patients who tested positive for the likelihood of response, and analyses combined patients with a positive test from both cohorts.
In Cohort 1, 135 patients were randomized, and a significantly higher percentage of those receiving tulisokibart achieved clinical remission compared to the placebo group (26% vs. 1%; difference, 25 percentage points; 95% confidence interval [CI], 14 to 37; P<0.001). In Cohort 2, 43 patients were enrolled. Across both cohorts, 75 patients tested positive for the likelihood of response. Among these patients, tulisokibart induced clinical remission in 32% of patients compared to 11% in the placebo group (difference, 21 percentage points; 95% CI, 2 to 38; P=0.02), demonstrating a statistically significant improvement.
Adverse events were similar between the tulisokibart and placebo groups, with most events classified as mild to moderate in severity. The study concluded that tulisokibart was more effective than placebo in inducing clinical remission in patients with moderately to severely active ulcerative colitis, particularly in those who tested positive for the genetic likelihood of response. These results suggest that tulisokibart could be a promising therapeutic option for this patient population.
Link to the article: https://www.nejm.org/doi/10.1056/NEJMoa2314076
References Sands, B. E., Feagan, B. G., Peyrin-Biroulet, L., Danese, S., Rubin, D. T., Laurent, O., Luo, A., Nguyen, D. D., Lu, J., Yen, M., Leszczyszyn, J., Kempiński, R., McGovern, D. P. B., Ma, C., Ritter, T. E., & Targan, S. (2024). Phase 2 trial of anti-tl1a monoclonal antibody tulisokibart for ulcerative colitis. New England Journal of Medicine, 391(12), 1119–1129. https://doi.org/10.1056/NEJMoa2314076
