DOP056Efficacy and Safety of Upadacitinib After 5 Years of Treatment in Patients With Moderately to Severely Active Ulcerative Colitis: Interim Analysis From the Phase 3 U-ACTIVATE Open-Label Extension Study

Abstract Background Clinical remission and endoscopic healing are long-term treatment targets for ulcerative colitis (UC). 1 U-ACTIVATE is an ongoing phase 3 long-term extension (LTE) study evaluating the efficacy and safety of upadacitinib (UPA), 2 an oral, selective Janus kinase inhibitor approved for adults with moderately to severely active UC. 3 Methods This interim analysis of the U-ACTIVATE LTE (NCT03006068) includes patients who responded to 8 weeks of UPA 45 mg once daily (QD) induction therapy and were then rerandomized to placebo (PBO), UPA 15 mg QD (UPA15), or UPA 30 mg QD (UPA30) for 52 weeks of maintenance therapy. Patients who completed maintenance, enrolled in the LTE and were assessed for an additional 192 weeks (total ∼ 5 years). At week 52 of maintenance, patients in clinical remission per adapted Mayo score entered the LTE and received open-label treatment. Nonremitters were eligible for blinded dose escalation in the LTE from maintenance PBO to UPA15 or from maintenance UPA15 to UPA30. Those who received maintenance UPA30 continued blinded UPA30. The study was not designed to compare UPA15 and UPA30 doses. Clinical remission per adapted Mayo score and partial Mayo score, maintenance of clinical remission per adapted Mayo score, achievement and maintenance of endoscopic improvement, and achievement and maintenance of endoscopic remission were assessed in this analysis at LTE week 192 as observed (AO) and by modified non-responder imputation (mNRI). Safety outcomes were treatment-emergent adverse events (TEAEs), presented as exposure-adjusted event rates (EAERs) ; cut-off date: June 30, 2025. Results In the AO analysis, most patients (69%) in both UPA treatment groups achieved clinical remission per adapted Mayo score and per partial Mayo score at LTE week 192 (Table 1). Of the patients in clinical remission per adapted Mayo score at LTE week 0, 80% maintained remission at LTE week 192 for both UPA doses. Most patients (80%) also achieved endoscopic improvement and maintained endoscopic improvement for both UPA doses. Endoscopic remission was achieved by 50% of patients at LTE week 192 for both UPA doses; 54% (UPA15) and 80% (UPA30) of remitters at LTE week 0 maintained remission at LTE week 192. The mNRI analysis also showed achievement and maintenance of efficacy outcomes (Table 1). EAERs for any TEAEs, serious TEAEs, and TEAEs that led to discontinuation were similar for both UPA doses (Table 2) and were consistent with previous analyses. 2, 4 Conclusion In the U-ACTIVATE OLE, UPA showed sustained clinical remission and endoscopic improvement at 5 years of treatment. The long-term safety profile of UPA was consistent with previous analyses. This analysis continues to support long-term UPA use in patients with UC. References: 1. Turner D, et al. , Gastroenterology. 2021;160: 1570–83. 2. Pannacione R, et al. Lancet Gastroenterol Hepatol. 2025;10: 507–19. 3. RINVOQ (Upadacitinib) Prescribing Information. Accessed June 20, 2025. https: //www. rxabbvie. com/pdf/rinvoqₚi. pdf 4. Pannacione R, et al. J Crohns Colitis. 2025;19Suppl₁: i84–6. Conflict of interest: Panaccione, Remo: Grant: Abbvie, Janssen, Pfizer, Takeda Other: Consultant for: Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Spyre Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, 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, SandozShire, Sublimity Therapeutics, Takeda Pharmaceuticals, Ventyx. Colombel, Jean-Frédéric: Grant: AbbVie, Janssen Pharmaceuticals, Takeda, Prometheus and Bristol Myers Squibb Lectures from: AbbVie, Roche and Takeda Other: AbbVie, Amgen, AnaptysBio, Allergan, Apini, Arena Pharmaceuticals, Astellas, Boehringer Ingelheim, Bristol Myers Squibb, candidrx Celgene, Celltrion, Clearview Curogen, Eli Lilly, Envision Pharma Ferring Pharmaceuticals, Galmed Research, Glaxo Smith Kline, Roche, Janssen Pharmaceuticals, Kaleido Biosciences, Immunic, Iterative Scopes, Landos, Microba Life Science, Merck, Mirador, Novartis, Otsuka Pharmaceutical, Owkin, Pfizer, Protagonist Therapeutics, Sanofi, Sun Pharma, Takeda, Teva, TiGenix, and is holding stock options in Intestinal Biotech Development Nakase, Hiroshi: has received research support from AbbVie Inc. , EA Pharma Co. , Ltd. , Janssen, JIMRO Corporation, Gilead Sciences, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. , Ltd. , Pfizer, Takeda Pharmaceutical Co. , Ltd. , Bristol-Myers Squibb, KYORIN Pharmaceutical Co. , Ltd, MIYARISAN Pharmaceutical Co. , Ltd, and has received grants from Hoya Group Pentax Medical. Dubcenco, Elena: is an employee of AbbVie Inc. and may own stock and/or options. Cheng, Erica: is an employee of AbbVie Inc. and may own stock and/or options. Kujawski, Michelle: Grant: Abbvie, Janssen, Pfizer, Takeda Other: Consultant for: Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Spyre Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, 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, SandozShire, Sublimity Therapeutics, Takeda Pharmaceuticals, Ventyx. Rizzo, Leah: is an employee of AbbVie Inc. and may own stock and/or options. Kasambira, Tafadzwa: is an employee of AbbVie Inc. and may own stock and/or options. Lichtenstein, Gary: has received consultancy fees from AbbVie Inc. , Bausch Health, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Johnson & Johnson, Med Ed Consultants (IBD Education Group), Merck, Pfizer, Pharmacosmos Therapeutics receiving continuing medical education sponsored by AbbVie, Eli Lilly, Focus Medical Communications (GI Health Foundation), Janssen Biotech, Merck, and Takeda, and Vindico has been on the Data Safet Monitoring Board for Eli Lilly, and received grants from Johnson & Johnson.