S1654 Risankizumab Effectiveness and Safety in Ulcerative Colitis: Real-World Data From a Large Tertiary Center

Introduction: Risankizumab (RZB) is an interleukin-23p19 inhibitor that was approved by the U.S. Food and Drug Administration in June 2024 for the treatment of moderately to severely active ulcerative colitis (UC). We report the real-world experience with RZB in UC in a large tertiary inflammatory bowel disease (IBD) center. Methods: This is a cohort study in which we prospectively recruited patients with UC at the UChicago IBD Center who were treated with RZB at standard labeled intravenous loading and maintenance dosing. We performed clinical assessments at baseline, weeks 2, 4, 8, 12, and 26, using the Simplified Clinical Colitis Activity Index (SCCAI) and fecal calprotectin (FCP). Clinical remission was defined as SCCAI ≤2 and/or FCP ≤150 µg/g. Steroid-free remission was defined as SCCAI ≤2 in the absence of steroid use. Adverse events were documented. Results were stratified based on prior exposure to ustekinumab (UST). Statistical analyses were performed using R v4.1.3. Results: Forty-nine patients were recruited, with 44 (90.0%) patients previously exposed to advanced therapies and 18 (36.7%) previously exposed to. Baseline median (interquartile range [IQR]) SCCAI and FCP were 3.0 (1.0-5.8) and 476.0 μg/g (105.2-1156.2), respectively. At week 8, median (IQR) SCCAI was 1.0 (0.0-2.0), with 31/41 (75.6%) in clinical remission and 29/41 (70.7%) in steroid-free remission. At week 26, the median (IQR) SCCAI was 1.0 (0.0-1.0), with 22/25 (88.0%) in clinical remission and 20/25 (80.0%) in steroid-free remission. Median (IQR) FCP over the study period (n = 29) was 109 μg/g (60-645), with 16/29 (55.2%) in biomarker remission, and similar in patients exposed to UST (n = 9, 79.9 μg/g [33.0-382.0]) and not exposed (n = 20, 114.5 μg/g [69.8-736.2]). Two (4.1%) patients were hospitalized for severe UC and no patients underwent colectomy. Four (8.2%) patients stopped RZB due to clinically active disease, and one (2.0%) patient stopped therapy due to a diffuse rash. Other adverse events included fatigue (n = 7, 14.3%), headache (n = 1, 2.0%), constipation (n = 1, 2.0%), and low-grade fever with the first infusion (n = 1, 2.0%). Conclusion: We present the largest real-world study of the effectiveness and safety of RZB in patients with UC, including patients previously exposed to UST. In this interim analysis, RZB is an effective and safe therapy for patients with moderately to severely active UC. Longer-term follow-up is ongoing.