S744 Risankizumab Induction Therapy Provides Early Symptom Improvements in Abdominal Pain and Stool Frequency in Patients With Moderate to Severe Crohn’s Disease: Results From Two Phase 3 Induction Studies

Introduction: Patient reported outcomes (PROs) including stool frequency (SF) and abdominal pain score (APS) are main drivers for disability and quality of life impairment in patients (pts) with Crohn’s disease (CD). We assess symptom improvement beginning at Wk1 with Risankizumab (RZB), an IL-23 p19 inhibitor, in pts with moderate to severe CD in two phase 3 induction studies, ADVANCE and MOTIVATE. Methods: Briefly, 50% of pts in ADVANCE and 100% in MOTIVATE showed prior inadequate response or intolerance to biologic therapy. Pts with moderate to severe CD (CD Activity Index [CDAI] of 220–450, Simple Endoscopic Score for CD [SES CD] ≥6 [≥4 for isolated ileal disease] excluding the narrowing component, and average daily [liquid/very soft] SF ≥4 and/or average daily AP score ≥2) were randomized 2:2:1 (ADVANCE) or 1:1:1 (MOTIVATE) to receive intravenous (IV) RZB 600 mg or 1200 mg, or placebo (PBO) as induction therapy at Wks 0, 4, and 8. Average daily SF and average daily AP scores were calculated from pt diary data. Enhanced clinical response (≥60% decrease in SF and/or ≥ 35% decrease in APS and both not worse than baseline [BL], and/or clinical remission), clinical remission per SF/APS (SF ≤2.8 and APS ≤1), SF remission (SF ≤2.8), AP remission (APS ≤1), and change from BL in SF and APS are reported using non-responder imputation. The Cochran-Mantel-Haenszel test was used for statistical comparisons of RZB dose and PBO. Safety was assessed in pts receiving at least 1 dose of study drug. Results: BL characteristics of pts enrolled in ADVANCE and MOTIVATE were generally well-balanced across treatment groups. A single IV dose of RZB, either 600 mg or 1200 mg, induced rates of enhanced clinical response and clinical remission per SF/APS that differentiated significantly from PBO as early as Wk2 (Table 1). Similarly, significant differences in proportion of pts achieving SF remission or APS remission alone were observed with RZB vs PBO (Table 1). Further, significant improvements from BL in average daily SF and APS were observed as early as Wk1 with RZB treatment (Table 1). No new safety risks were identified and both induction doses of RZB were well tolerated. Conclusion: RZB induction therapy led to early improvements in clinical symptoms of AP and SF with early significant differentiation from placebo in pts with moderate to severe CD. Significant differentiation in clinical response and remission from placebo could be achieved with RZB treatment as early as Wk2.Table 1.: Adverse events.

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