Adv Ther. 2024 Oct;41(10):3832-3849.doi: 10.1007/s12325-024-02912-y. Epub 2024 Aug 10.

Walter Reinisch ¹, Gil Y Melmed ², Hiroshi Nakase ³, Jakob Seidelin ⁴, Christopher Ma ^5 6, Si Xuan ⁷, Jacinda Tran ^7 8, Valencia Remple ⁷, Lani Wegrzyn ⁷, Gweneth Levy ⁷, Yuri Sanchez Gonzalez ⁷, Remo Panaccione ⁶

Author information

¹Department Internal Medicine III, Division Gastroenterology & Hepatology, Medical University Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. walter.reinisch@meduniwien.ac.at.

²Cedars-Sinai Medical Center, Los Angeles, CA, USA.

³Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan.

⁴Department of Gastroenterology and Hepatology, Copenhagen University Hospital-Gentofte and Herlev, Herlev, Denmark.

⁵Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.

⁶Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada.

⁷AbbVie Inc., North Chicago, IL, USA.

⁸The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, University of Washington, Seattle, WA, USA.

Abstract

Introduction: Evidence on the comparative efficacy and safety of approved therapies for ulcerative colitis (UC) during induction and maintenance, including upadacitinib (UPA), vedolizumab (VEDO), ustekinumab (UST), and tofacitinib (TOFA), is limited.

Methods: Using data from phase 3 trials, three placebo (PBO)-anchored matching-adjusted indirect comparisons of the efficacy and safety of UPA versus VEDO, UST, and TOFA (U-ACHIEVE and U-ACCOMPLISH, GEMINI-1, UNIFI, and OCTAVE induction and maintenance trials) have been conducted. Baseline characteristics from UPA trials were weighted separately to match each comparator trial. Induction responders were re-randomized to oral UPA 15 or 30 mg, VEDO 300 mg intravenously every 8 weeks (Q8W), UST 90 mg SC Q8W, or oral TOFA 5 mg, or PBO in maintenance. Treat-through efficacy outcomes at weeks 44(UST)/46(VEDO)/52(UPA/TOFA) were adjusted by the likelihood of induction response and included clinical response, clinical remission, and endoscopic improvement. Safety outcomes included adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation (except UPA vs. VEDO). Benefit-risk was assessed by numbers needed to treat (NNT)/harm, calculated as the inverse of the difference in proportions of patients achieving each efficacy/safety outcome for UPA versus comparator.

Results: The proportions of patients who demonstrated clinical response or endoscopic improvement was greater with UPA 15 mg versus VEDO and TOFA (p < 0.05). The proportions of patients demonstrating all treat-through efficacy outcomes were significantly greater with UPA 30 mg versus VEDO, UST, or TOFA with NNTs 3.2-8.7. No significant differences in proportions of AEs, SAEs, and AEs leading to discontinuation were observed between the two doses of UPA and comparators.

Conclusion: In patients with active UC, greater clinical efficacy, and similar safety after 1 year of maintenance were observed with UPA versus VEDO, UST, and TOFA, suggesting a favorable benefit-risk profile for UPA. Despite matched baseline characteristics, differences in trial design and endpoints may persist.