S1162 PRA023 Improved Bowel Urgency, Nocturnal Bowel Movement, Nocturnal Waking, and Abdominal Pain in a Phase 2 Trial of Patients With Moderately to Severely Active Ulcerative Colitis

Introduction: PRA023 is an anti–tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody in development for treating inflammatory bowel diseases. In Cohort 1 of a phase 2, double-blind, placebo-controlled trial (ARTEMIS-UC) that enrolled patients with moderately to severely active ulcerative colitis (UC), PRA023 achieved the primary endpoint of clinical remission and all ranked secondary endpoints for this cohort after 12 weeks of induction therapy. In a post hoc analysis, we assessed the impact of PRA023 on UC-associated health-related symptoms, including bowel urgency, nocturnal bowel movements (BM), and abdominal pain. Methods: Adults with a modified Mayo score of 4 to 9, centrally read endoscopy subscore ≥2, rectal bleeding subscore ≥1, and history of corticosteroid dependence or insufficient response, loss of response, and/or intolerance to conventional and/or advanced therapies were randomized 1:1 to placebo or intravenous PRA023 (1000 mg on day 1, and 500 mg at weeks 2, 6, and 10). Patients recorded nocturnal BM and bowel urgency daily with an electronic diary. Bowel urgency during the prior 24 hours was measured using the Urgency Numeric Rating Scale (UNRS 0 [no urgency] to 10 [worst possible urgency]). For patients with baseline UNRS ≥3, clinically meaningful improvement (CMI) was defined as ≥3-point decrease, and bowel urgency remission was defined as a score of ≤1, where nonresponder imputation was applied to the missing data. Nocturnal waking and abdominal pain were reported via the Inflammatory Bowel Disease Questionnaire at baseline and week 12. Results: Of 127 patients with baseline UNRS ≥3, a significantly greater proportion of patients receiving PRA023 achieved CMI in bowel urgency (52.4% PRA023 vs 20.3% placebo, ∆32.1%, P=0.0002) and bowel urgency remission (22.2% PRA023 vs 3.1% placebo, ∆19.1%, P=0.0013) at week 12. A significant decrease in bowel urgency and nocturnal BM was observed as early as week 2 and was improved further throughout the 12-week induction period (Figure 1). Nocturnal waking and abdominal pain were significantly improved in patients treated with PRA023 compared to placebo. The least-squares mean (SE) change in rating scale from baseline to week 12 in PRA023 treated patients compared to placebo was 1.74 (0.21) vs 0.87 (0.22) for nocturnal waking and 1.62 (0.17) vs 0.93 (0.18) for abdominal pain. Conclusion: In patients with moderately to severely active UC, PRA023 significantly decreased bowel urgency, nocturnal BM, nocturnal waking, and abdominal pain.Figure 1.: Change from Baseline in Bowel Urgency (A) and Nocturnal Bowel Movements (B) Over 12 Weeks of Treatment with PRA023 Data are least squares mean ± SE change from baseline in response to the following daily diary questions: (A) On a scale of 0 to 10, have you experienced any urgency with your bowel movements? or (B) Of the bowel movements over the last 24 hours, how many required your waking up from sleep? **P<0.01; ***P<0.001.

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