S1873 Extraintestinal Manifestations and Disease Characteristics in Crohn’s Disease Patients on Risankizumab or Ustekinumab

Introduction: An estimated 40% of patients with inflammatory bowel disease (IBD) have comorbid extraintestinal manifestations (EIMs). Risankizumab (RZB), a selective interleukin (IL)-23 antagonist, may be more effective and have fewer adverse effects in Crohn’s disease (CD) treatment than ustekinumab (UST), an IL-12/23 antagonist. The real-world effect of risankizumab on EIMs in CD is unknown. We present analyses of CD patients with EIMs on RZB or UST. Methods: We performed a retrospective cohort study for CD patients treated with RZB or UST for at least 8 weeks between 7/2022-8/2024 and 3/2009-1/2019, respectively. Patients with current or previously–active EIMs (rheumatologic, dermatologic, ophthalmologic, or hepatobiliary) were included for analysis. Baseline demographics, disease characteristics, and EIM activity were noted, with improvement or resolution of EIMs by last follow up (up to 1 year) as the primary outcome of interest. Secondary outcomes included the follow-up Harvey-Bradshaw Index (HBI), IBD clinical and biochemical remission (no steroids & HBI ≤4; CRP ≤0.9 mg/dL & fecal calprotectin <250 ug/g), and the Simple Endoscopic Score for Crohn’s Disease (SES-CD). Results: 127 patients (RZB: 86, UST: 41) met inclusion criteria, with a mean age of 41 ± 16 years and mean follow-up of 309 ± 135 days. Forty-five patients had multiple EIMs. Most had rheumatologic EIMs (93%), followed by dermatologic (29%), ophthalmologic (11%), and hepatobiliary (1.6%). A lower proportion of patients on RZB had elevated CRP or active EIMs at baseline compared to UST (23% vs 61%, P = 0.005; 67% vs 88%, P = 0.02). Patients on RZB and UST had similar rates of EIM improvement or resolution (62% vs 69%, P = 0.61). RZB was associated with a longer mean time to improvement of any EIM (224 vs 108 days, P < 0.001) as well as rheumatologic (220 vs 110 days, P < 0.001) and dermatologic EIMs (267 vs 126 days, P = 0.025). Patients on RZB had lower HBI scores than those on UST at baseline (6.81 vs 10.00, P = 0.01) and at follow-up (3.23 vs 5.41, P = 0.06). There was no significant difference between RZB and UST for clinical remission, biochemical remission, or SES-CD (3.43 vs 7.23, P = 0.3). Conclusion: The majority of patients on both RZB and UST had improvement or resolution of EIMs in the first year of therapy, though patients on RZB may have a slower response for rheumatologic or dermatologic EIMs. Further understanding of the effectiveness of RZB on EIMs will help inform positioning of CD therapies.