S1589 Effect of Subcutaneous Guselkumab on Bowel Urgency and Abdominal Pain as Measured by the UC-PRO/SS in Participants With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 ASTRO Study

Introduction: Guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, demonstrated efficacy in participants (pts) with moderately to severely active ulcerative colitis (UC) treated with GUS subcutaneous (SC) induction and maintenance in the Phase 3 ASTRO study. Here, we present data for bowel urgency and abdominal pain symptoms as measured by the Ulcerative Colitis Patient-Reported Outcomes Signs and Symptoms (UC-PRO/SS) instrument through Week (W) 24. Methods: Eligible pts had a modified Mayo score of 5 to 9, a rectal bleeding subscore of ≥1, and a Mayo endoscopic subscore (MES) ≥2. Pts had a documented inadequate response/intolerance to biologics, Janus kinase (JAK) inhibitors, and/or sphingosine-1-phosphate (S1P) inhibitors (BIO/JAKi/S1Pi-IR) or to corticosteroids, 6-mercaptopurine, or azathioprine. Randomization was stratified by baseline BIO/JAKi/S1Pi-IR status and MES with 418 pts allocated 1:1:1 to GUS 400 mg SC every 4 weeks (every 4 weeks) (x3)→GUS 200 mg SC every 4 weeks (N = 140), GUS 400 mg SC every 4 weeks (x3)→GUS 100 mg SC every 8 weeks (every 8 weeks) (N = 139), or placebo (PBO) (N = 139). Pts who met rescue criteria at W16 were rescued: PBO pts switched to GUS; GUS pts stayed on their assigned GUS dose regimen (sham rescue). The UC-PRO/SS is a validated instrument to assess the severity of bowel-related symptoms. Clinically meaningful improvements (CMI) in bowel signs and symptoms and abdominal symptoms scales were evaluated. Complete resolution of individual core symptoms (bowel urgency and abdominal pain) was assessed. Results: GUS-treated pts achieved greater improvement from baseline through W24 in domain and individual core symptoms compared with PBO-treated pts. The proportions of pts achieving CMI in each domain score were also greater for GUS vs PBO. Among pts with bowel urgency symptoms at baseline, 45.0% receiving GUS had resolution of bowel urgency by W12 compared with 23.1% for PBO, and these levels were maintained through W24. Among pts with abdominal pain symptoms at baseline, 48.8% receiving GUS had resolution of abdominal pain by W12 compared with 23.9% for PBO, and these levels were also maintained through W24. Conclusion: Pts with moderately to severely active UC treated with GUS SC experienced clinically meaningful improvements through W24 in UC signs and symptoms as measured by UC-PRO/SS compared with PBO.