Phase 2 Trial of Anti-TL1A Monoclonal Antibody Tulisokibart for Ulcerative Colitis.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Corporate Authors:
      ARTEMIS-UC Study Group
    • Source:
      Publisher: Massachusetts Medical Society Country of Publication: United States NLM ID: 0255562 Publication Model: Print Cited Medium: Internet ISSN: 1533-4406 (Electronic) Linking ISSN: 00284793 NLM ISO Abbreviation: N Engl J Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: Boston, Massachusetts Medical Society.
    • Subject Terms:
      Antibodies, Monoclonal*/administration & dosage ; Antibodies, Monoclonal*/adverse effects ; Colitis, Ulcerative*/diagnosis ; Colitis, Ulcerative*/drug therapy ; Remission Induction*/methods ; Tumor Necrosis Factor Ligand Superfamily Member 15*/antagonists & inhibitors; Adult ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Infusions, Intravenous ; Treatment Outcome
    • Abstract:
      Background: Tulisokibart is a tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody in development for the treatment of moderately to severely active ulcerative colitis. A genetic-based diagnostic test was designed to identify patients with an increased likelihood of response.
      Methods: We randomly assigned patients with glucocorticoid dependence or failure of conventional or advanced therapies for ulcerative colitis to receive intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10) or placebo. Cohort 1 included patients regardless of status with respect to the test for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response. The primary analysis was performed in cohort 1; the primary end point was clinical remission at week 12. Patients with a positive test for likelihood of response from cohorts 1 and 2 were combined in prespecified analyses.
      Results: In cohort 1, a total of 135 patients underwent randomization. A significantly higher percentage of patients who received tulisokibart had clinical remission than those who received placebo (26% vs. 1%; difference, 25 percentage points; 95% confidence interval [CI], 14 to 37; P<0.001). In cohort 2, a total of 43 patients underwent randomization. A total of 75 patients with a positive test for likelihood of response underwent randomization across both cohorts. Among patients with a positive test for likelihood of response (cohorts 1 and 2 combined), clinical remission occurred in a higher percentage of patients who received tulisokibart than in those who received placebo (32% vs. 11%; difference, 21 percentage points; 95% CI, 2 to 38; P = 0.02). Among all the enrolled patients, the incidence of adverse events was similar in the tulisokibart and placebo groups; most adverse events were mild to moderate in severity.
      Conclusions: In this short-term trial, tulisokibart was more effective than placebo in inducing clinical remission in patients with moderately to severely active ulcerative colitis. (Funded by Prometheus Biosciences, a subsidiary of Merck; ARTEMIS-UC ClinicalTrials.gov number, NCT04996797.).
      (Copyright © 2024 Massachusetts Medical Society.)
    • Contributed Indexing:
      Investigator: G Holtmann; J Fon; R Leong; J Begun; K Lynch; M Sparrow; J Sabino; E Louis; C Ma; M Silverberg; B Bressler; D Stepek; T Vanasek; J Pumprla; X Roblin; Y Bouhnik; X Hebuterne; L Peyrin-Biroulet; P Desreumaux; G Boschetti; T Telia; R Schnabel; M Varga; T Gyokeres; P Miheller; D Schwartz; E Zittan; E Israeli; IA Biron; A Gasbarrini; S Danese; M Horynski; R Petryka; A Wiechowska-Kozlowska; L Puszko; A Kopon; M Woynarowski; P Wojciech; P Rozpondek; J Leszczyszyn; J Kierkus; R Kempinski; P Ramos; Ł Hordecki; S Wieczorek; M Kowalski; P Walczak; W Danilkiewicz; P Zając; S Hoque; M Munisamy; B Monaghan; S Mon; B Boland; J Bullock; T Ritter; J Liu; R Fogel; R Longman; Z Salam; G Melmed; A Steinlauf; W Holderman; GA DuVall; A Ali; AK Houssam; C Bartalos; A Tuskey; HE Sarles; ZH Younes; MA Youssef; T Esfandyari; J Rosenberg; R Shaughnessy; N Merel; M Bernsen; RB Gaible
    • Molecular Sequence:
      ClinicalTrials.gov NCT04996797
    • Accession Number:
      0 (Antibodies, Monoclonal)
      0 (TNFSF15 protein, human)
      0 (Tumor Necrosis Factor Ligand Superfamily Member 15)
    • Publication Date:
      Date Created: 20240925 Date Completed: 20240925 Latest Revision: 20240928
    • Publication Date:
      20240929
    • Accession Number:
      10.1056/NEJMoa2314076
    • Accession Number:
      39321363