S1964 Comparable Gastrointestinal Side Effects and Steroid Use in Anti-TNF–Naïve Ulcerative Colitis Patients Treated With Risankizumab or Guselkumab: A National Database Analysis

Introduction: Interleukin-23 (IL-23) is a pro-inflammatory cytokine that plays a central role in the pathogenesis of ulcerative colitis (UC). Because of its key role in the inflammatory cascade, IL-23 is a major therapeutic target in UC. There is paucity of data comparing the use of risankizumab vs guselkumab, both IL-23 inhibitors. Therefore, we aim to evaluate the outcomes of anti-TNF naïve patients with UC taking risankizumab or guselkumab. Methods: We performed a retrospective cohort study utilizing large population-based data from the TriNetX platform. We identified anti-TNF naïve patients with UC who received risankizumab between January 1, 2024, and May 31, 2025. This cohort of patients was matched anti-TNF naïve patients with UC who received guselkumab according to age, demographics, comorbidities, and medication by using 1:1 propensity matching. The endpoints were gastrointestinal (GI) side effects (abdominal pain, nausea/vomiting, diarrhea, constipation and gastroesophageal reflux disease) and intravenous (IV) or oral corticosteroid use. Logistic regression was used to estimate odd ratios (ORs). Results: A total of 729 anti-TNF–naïve adult patients with UC were identified, 634 of these individuals were taking risankizumab; 91 out of 634 (mean [SD] age, 43.6 [17.4] years; 38 [58.2%] female) were matched with 91 individuals (mean [SD] age, 44.9 [17.2] years; 49 [53.84%] female) who were taking guselkumab. No differences were found in the incidence of GI side effects and use of IV or oral steroid use. The risankizumab group notable for having 10 patients with nausea and vomiting when compared with no patients in the guselkumab group; however, unable to measure of association between an exposure and an outcome due to lack of events in the guselkumab group. Conclusion: In anti-TNF–naïve patients with UC, treatment with risankizumab or guselkumab resulted in similar rates of GI side effects except for nausea and vomiting seen only in patients using risankizumab. There was no significant difference in the need for IV or oral corticosteroid use between the 2 therapies. These findings suggest comparable safety and steroid-sparing potential for both agents in this patient population. Further prospective studies are needed to determine the mechanism for these clinical findings.