P0895Long-Term Efficacy of Upadacitinib in Patients With Moderate-to-Severe Crohn’s Disease and Prior Biologic Use

Abstract Background The long-term efficacy and safety of the selective JAK inhibitor upadacitinib (UPA) in patients with moderate-to-severe Crohn’s disease (CD) are currently being evaluated in the ongoing U-ENDURE long-term extension (LTE) study.1 Here, we report the efficacy of 2 years of UPA treatment in the U-ENDURE LTE (3 years of total maintenance treatment) stratified by prior inadequate response or intolerance to biologic therapy (Bio-IR) at baseline. Methods This post hoc analysis included patients who completed 52 weeks of maintenance treatment in U-ENDURE and continued their previously assigned treatment (UPA 15 mg UPA15 or UPA 30 mg UPA30 once daily QD) for an additional 96 weeks in the LTE study. Patients who demonstrated IR to UPA during the treatment period and required medical treatment could receive rescue therapy. Efficacy outcomes during the LTE were assessed by baseline Bio-IR status (yes, no) and included clinical remission (per CD activity index CDAI and per stool frequency/abdominal pain score SF/APS), endoscopic response, endoscopic remission, ulcer-free endoscopy, and deep remission (endpoints defined in Figure footnotes). Data are presented as observed (AO). All available measurements before initiation of rescue were analysed; values for missing data were not imputed.1 Safety by Bio-IR status has been reported previously.2 Results In the Bio-IR group, 70 patients received UPA15, and 119 patients received UPA30; in the nonBio-IR group, 37 patients received UPA15, and 54 patients received UPA30. From week 0 to week 96 of the LTE, ≥ 63.0% of patients achieved and sustained clinical remission per SF/APS, and ≥ 59.1% of patients achieved and sustained endoscopic response, in both Bio-IR and nonBio-IR subgroups, irrespective of treatment group (Figure). In both subgroups and treatment groups, ≥ 71.0% of patients achieved and sustained clinical remission per CDAI throughout the LTE. For the endoscopic endpoints of remission and ulcer-free endoscopy, as well as the clinical and endoscopic composite endpoint of deep remission, efficacy rates were either sustained during the 96-week LTE or were numerically higher at week 96 versus week 0 in both Bio-IR and non-Bio-IR patients, irrespective of UPA treatment group. Conclusion Sustained clinical and endoscopic efficacy was observed in patients who completed up to 3 years of UPA maintenance therapy in U-ENDURE, regardless of Bio-IR status at baseline. This analysis supports the long-term efficacy of UPA in patients with CD regardless of prior inadequate response or intolerance to biologic therapy. References: 1. Loftus, Jr EV, J Crohn’s Colitis. 2025;19(8):jjaf138. 2. Peyrin-Biroulet L Clin Gastroenterol Hepatol. 2024;22(10):2096-2106. Conflict of interest: Atreya, Raja: RA has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AlfaSigma, Arena Pharmaceuticals, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Dr Falk Pharma, Galapagos, Gilead, GlaxoSmithKline, InDex Pharmaceuticals, Johnson & Johnson, Lilly, Materia Prima, Merck Sharpe & Dohme, Pfizer, Roche Pharma, Takeda Pharma, Viatris. Panaccione, Remo: Consultant for: Abbott, AbbVie, Abbivax, Alimentiv,Amgen, AnaptysBio, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Inviva,Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mirador, Novartis, Oppilan Pharma, Odyssey, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Sanofi, Satisfai Health, Shire, Sublimity Therapeutics, Spyre Therapeutics, Takeda Pharmaceuticals, Teva,, Tillots, Trellus, Union Biopharma, Viatris, Ventyx, UCB Speaker’s Fees for: AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda Pharmaceuticals Advisory Boards for: AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Sanofi, Sublimity Therapeutics, Takeda Pharmaceuticals, Ventyx. Louis, Edouard: Education and Reserach Grants for my department: Abbvie, Takeda, Johnson and Johnson, Pfizer, Fresenius-Kabi, Celltrion, EG pharma, Sandoz, Falk Personal Fees for conferences, advisory boards and consultancy: Abbvie, Takeda, Ferring, Pfizer, Johnson and Johnson, Lilly, Galapagos, Celltrion, Arena, BMS, Falk, Biokuris, Fresenius-Kabi, Thabor Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx. Cunneen, Colla: A full-time employee of AbbVie and may own AbbVie stock or options. Garrison, Andrew: Contractor at AbbVie and may own AbbVie stock or options. Dubcenco, Elena: Full-time employee of AbbVie and may own AbbVie stock or options. Naling, Grace: Full-time employee of AbbVie and may own AbbVie stock or options. El Ouali, Sara: Speaker and/or consulting fees from Takeda, Eli Lilly, Janssen, Abbvie.