S1458 Real-World Comparison of Upadacitinib and Ustekinumab for Ulcerative Colitis: A Propensity-Matched Analysis

Introduction: Upadacitinib (UPA), a selective Janus kinase-1 inhibitor, and ustekinumab (USTE), an interleukin-12/23 inhibitor, are approved for the treatment of moderate-to-severe ulcerative colitis (UC). Real-world head-to-head comparative data between these therapies remain limited. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, a federated electronic health record database. Adult patients with UC who were on UPA or USTE between April 2022 and April 2024 were identified. Patients were excluded for co-diagnoses of Crohn’s disease or if they previously underwent total colectomy. Propensity score matching (1:1) was performed on demographics, prior medication use (prednisone, azathioprine, mesalamine, infliximab, adalimumab), and laboratory values (albumin, CRP, fecal calprotectin). The primary outcome was systemic corticosteroids use. Secondary outcomes included emergency department (ED) visit and composite outcome of major cardiovascular events or thrombosis (pulmonary embolism and deep vein thrombosis). Results: A total of 1,169 patients in the UPA cohort and 2,680 in the USTE cohort met inclusion criteria. After matching, 1,146 patients remained in each cohort, with balanced baseline characteristics. At 1-year follow-up, the primary outcome (corticosteroid use) occurred in 39.4% of patients in the UPA group and 43.7% in the USTE group (RR = 0.90, 95% CI: 0.82–0.99, P = 0.038). ED visits occurred in 14.5% vs 12.9%, respectively (RR = 1.12, 95% CI: 0.91–1.34, P = 0.27). The composite outcome of major cardiovascular events or thrombosis occurred in 1.29% vs 0.95% (RR = 1.37, 95% CI: 0.61,3.063, P = 0.4464). Conclusion: In this real-world analysis, treatment with UPA was associated with lower rates of corticosteroid use compared to USTE in patients with ulcerative colitis over 1 year. There was no statistically significant difference in the emergency department admissions. These findings indicates potential higher effectiveness of UPA in UC compared to USTE and may inform treatment selection.