Presentation Information
[WS4-4]Relationship between symptom resolution and clinical responses after 12 weeks of treatment with tulisokibart in patients with moderately to severely active ulcerative colitis
*Yu Sakamoto1, Christopher Ma2, Brigid S Boland3, Rupert W Leong4, Marek Horynski5 (1. Clinical Research, Japan Development, MSD K.K.、2. Division of Gastroenterology & Hepatology, Departments of Medicine and Community Health Sciences, University of Calgary、3. Altman Clinical Translational Research Institute, University of California, San Diego、4. Macquarie University、5. Endoskopia sp. z o.o.)
Introduction: Tulisokibart, an anti-TL1A monoclonal antibody, has demonstrated significantly higher rates of clinical remission and endoscopic and histologic improvements vs placebo in participants with moderately to severely active ulcerative colitis in a phase 2 double-blind, placebo-controlled induction clinical trial. In this post hoc analysis, we assessed the relationship between rectal bleeding (RB), stool frequency (SF), and bowel urgency (BU) resolution and clinical responses after 12 weeks of treatment with tulisokibart.
Methods: Adults with moderately to severely active UC were randomized 1:1 to receive placebo or intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10). BU was recorded daily with the Urgency Numeric Rating Scale (UNRS); resolution was defined as UNRS ≤1. RB and SF were recorded daily by participants; resolution was defined as SF subscore ≤1 or RB subscore of 0. A mixed model repeated measures approach was used to compare tulisokibart with placebo for change from baseline in UNRS.
Results: Of the 135 randomized patients, 60/67 (89.6%) receiving placebo and 68/68 (100%) receiving tulisokibart completed the 12-week induction period. Tulisokibart treatment led to a significant reduction in UNRS by week 2, continuing through week 12 (difference from placebo at week 12, -1.76; p<0.001). At week 12, patients who reported BU resolution experienced higher rates of clinical remission, clinical response, and endoscopic improvement than those who did not. Two component patient reported outcome (PRO2) remission at week 2 and week 6 appeared to be positively associated with clinical remission at week 12.
Conclusions: In patients with moderately to severely active UC, tulisokibart led to rapid symptom improvement. BU resolution was associated with clinical remission, clinical response, and endoscopic improvement. Of the patient-reported outcomes, improvement in SF was the strongest predictive measure for clinical remission at week 12. Of the mMS components, an ES subscore ≤1 showed the highest concordance with clinical remission at week 12.