S1805 Long-Term Safety of Ustekinumab vs Risankizumab in Biologic-Naive Inflammatory Bowel Disease Patients: Insights From a Retrospective Study

Introduction: Biologic agents have revolutionized the management of inflammatory bowel disease (IBD) over the past 2 decades. While these therapies effectively induce and maintain remission, understanding their safety profiles is essential for long-term management. This study compares the long-term safety of ustekinumab and risankizumab in biologic-naive IBD patients, focusing on key adverse events. Methods: Using the TriNetX database, we identified biologic-naive IBD patients who initiated ustekinumab or risankizumab between January 2020 and December 2023 and had no prior cancer history. Propensity score matching balanced baseline age, gender, race, and disease severity, forming 2 cohorts: ustekinumab (n = 329) and risankizumab (n = 329). Safety outcomes, including cancers, infections, thromboembolism, and hospitalizations, were evaluated at 3 and 5 years. Kaplan-Meier analysis assessed the probabilities of remaining free from adverse events. Results: At 3 years, infection-free probabilities were lower for risankizumab (42.7%) compared to ustekinumab (72.2%, P = 0.345), despite similar infection event rates (19.5% vs 18.2%). Cancer-free probabilities remained comparable between the 2 cohorts (95.3% for ustekinumab vs 92.6% for risankizumab, P = 0.400). Similarly, thromboembolism-free and hospitalization-free probabilities showed no significant differences. These trends persisted at 5 years with no statistically significant differences observed in overall safety outcomes. However, the notable and consistent gap in infection-free probabilities warrants further investigation to clarify its clinical relevance. Conclusion: The 3- and 5-year follow-up data indicate that ustekinumab and risankizumab have comparable safety profiles, with no significant differences in rates of cancer, thromboembolism, or hospitalizations. However, the lower infection-free probability for risankizumab highlights a potential trend that may become clinically relevant with larger sample sizes or longer follow-up. These findings support the safe, long-term use of both biologics but underscore the need for individualized safety monitoring, particularly for infection risk. Future studies should explore whether these differences reflect inherent drug properties or incidental findings.