P0784Comparative Effectiveness of Upadacitinib vs Tofacitinib on Clinical Outcomes in Ulcerative Colitis: A Propensity-Matched Cohort Study

Background Tofacitinib and upadacitinib are advanced therapies for moderate-to-severe ulcerative colitis (UC), but real-world comparative effectiveness data remain limited. This study assessed differences in infection risk, cardiovascular complications, gastrointestinal outcomes, and healthcare utilization among UC patients treated with upadacitinib versus tofacitinib. Methods Using the TriNetX U.S. Collaborative Network, we conducted a retrospective cohort study of adults (≥18 years) with UC treated with upadacitinib (Cohort 1) or tofacitinib (Cohort 2) between 2020–2024. Patients with Crohn’s disease, indeterminate colitis, malignancy, or positive pregnancy tests were excluded. Propensity score matching (1:1) yielded 741 patients per cohort balanced across demographics and comorbidities. Outcomes assessed over 730 days included infection, cardiovascular (CV) events (AMI, stroke, DVT/PE), hospital admissions, abdominal pain, gastrointestinal bleeding (GIB), abscess formation, and steroid use. Acute pancreatitis was prespecified as an outcome, but TriNetX returned insufficient patient events to allow statistical analysis. Outcome measures included odds ratios (OR), risk ratios, and hazard ratios (HR). Results Upadacitinib-treated patients had significantly lower rates of hospital admission (12.4% vs 17.9%; OR 0.648, 95% CI 0.486–0.864; p = 0.003). Numerical reductions were observed in infection (9.4% vs 10.3%), CV events (2.7% vs 3.5%), abdominal pain (26.9% vs 29.1%), GIB (17.4% vs 20.6%), abscess (1.8% vs 2.8%), and steroid use (55.2% vs 57.8%), though none reached statistical significance. Kaplan-Meier analyses showed improved survival free of hospital admission in the upadacitinib cohort. Acute pancreatitis could not be evaluated due to insufficient case counts returned by the network. Conclusion In this real-world matched analysis, upadacitinib was associated with significantly lower hospitalization risk compared with tofacitinib among UC patients, with favorable non-significant trends across multiple additional clinical outcomes. Although acute pancreatitis was included as a prespecified endpoint, no analyzable data were returned. These findings support upadacitinib as a potentially more effective option for reducing healthcare utilization in UC, warranting further comparative research. Conflict of interest: Dr. Patel, Om: No conflict of interest Johal, Jashanveer: No conflict of interest Al-Bataineh, Mahmoud: No conflict of interest Hussein, Abdallah: No conflict of interest Schneider, Yecheskel: No conflict of interest Hyman, Jason: No conflict of interest