834 Early Symptom Improvement With Risankizumab Treatment in Patients With Moderately to Severely Active Crohn’s Disease: Analysis From a Phase 2 Study

Abstract

INTRODUCTION: Risankizumab (RZB), an IL-23 p19 inhibitor, has shown safety and efficacy in inducing clinical remission in patients with Crohn’s disease (CD) in a Phase 2 study.1 Here we assessed early symptom improvement during the randomized, double-blind, placebo-controlled induction phase of the trial. METHODS: This Phase 2 study enrolled adult patients with moderate-to-severe CD with a Crohn’s Disease Activity Index (CDAI) of 220–450, ulcers in the ileum and/or colon, and a Crohn’s Disease Endoscopic Index of Severity (CDEIS) ≥7 (≥4 for patients with isolated ileitis) assessed by ileocolonoscopy confirmed by a blinded central reader. Patients were randomized 1:1:1 to receive intravenous RZB (200 mg or 600 mg) or placebo at Weeks 0, 4, and 8. Endpoints examined in this post hoc analysis included changes from baseline at Weeks 2, 4, 8, and 12 in CDAI, average daily stool frequency (SF) and average daily abdominal pain score (AP) for all patients with available data, and newly defined clinical remission at Week 12, based on symptom improvement, defined as SF ≤ 2.8 and AP ≤1, both not worse than baseline, in patients with baseline SF ≥ 4 or AP ≥2. Continuous endpoints were analyzed using observed case; non-responder imputation was used for missing data of binary endpoints. Statistical comparisons of median change were based on Wilcoxon rank sum test. RESULTS: 121 patients were randomized in the induction phase. Baseline characteristics were similar among treatment arms.1 Mean (SD) disease duration at baseline was 13.4 (9.4) years; 94.2% of patients received previous anti-TNF therapy. Significant improvements in CDAI and AP were observed with RZB (600 mg) versus placebo as early as Week 2 and in SF at Week 8 (Table 1). The proportion of patients with clinical remission based on symptom improvement was significantly higher in the 600 mg RZB group versus placebo at Week 12 (23.7% versus 6.1%; P < 0.05), supporting the previously reported superiority of RZB versus placebo for inducing CDAI remission at Week 12 (36.6% of 600 mg RZB versus 15% of placebo; P < 0.05). CONCLUSION: RZB induction treatment was associated with significant early improvements in clinical symptoms and disease activity in a highly refractory patient population with moderately to severely active CD.