P0652Real-World Effectiveness of Upadacitinib in Patients With Moderate-to-Severe Ulcerative Colitis: Interim Findings on Treatment Patterns From the PROFUNDUS Study

Abstract Background Upadacitinib (UPA), an oral and reversible Janus kinase inhibitor (JAKi), is approved for the treatment of moderate-to-severe ulcerative colitis (UC).1,2 Although pivotal trials support its use, real-world (RW) evidence on UPA in UC remains limited.3 This interim analysis of the open-label Prospective Real-World Study of UPA in UC (PROFUNDUS) evaluates treatment patterns among patients with UC in RW practice. Methods Eligible patients included adults (18-79 years yrs) with moderate-to-severe UC initiating UPA across 16 countries; decisions were made by investigators in line with local guidelines. Tapering of steroids was not mandated, as this was at the discretion of the investigator. This interim analysis evaluated the full analysis set (FAS), which comprised 494 of the first 500 eligible patients who provided informed consent and initiated once-daily UPA according to the local label. Baseline (BL) demographics, clinical characteristics, discontinuation reasons, and CS use at the end of induction and maintenance wk 26 were evaluated in FAS patients and by advanced therapy (AT) status (AT-experienced vs AT-naive; cut-off date: 28Feb2025). Results Among FAS at BL (last measurement on or before the initial dose), the mean (SD) patient age was 39.4 (13.3) yrs, with 57.1% males, and 21.5% on CS; mean (SD) disease duration was 7.8±7.0 yrs, with 54.6% of patients being AT-experienced, and 14.2% failed ≥1 JAKi. At wk 26, 82.8% of patients remained on UPA (AT-experienced: 79.6%; AT-naive: 86.6%; Table 1). The most common reasons for discontinuation were adverse events (6.3%), lack of efficacy (2.8%), and patient withdrawal (2.6%; Table 1). Within the overall population, most patients were on UPA30 at the initiation of maintenance and at wk 26 (88.7%, 80.6%), with fewer on UPA15 (11.3%, 14.1%); a numerically greater proportion of AT-experienced patients remained on UPA30 (84.2% vs 76.4%) or were escalated to UPA45 (6.1% vs 4.2%) by wk 26 compared with AT-naïve patients (Table 2). Of those on CS at BL, approximately half (52.2%) remained on CS at the end of induction among patients on any UPA dose (AT-experience: 58.9% vs AT-naive: 41.7%), which decreased to 33.9% at wk 26, with a comparable distribution across subgroups (Table 2). Safety data from PROFUNDUS are not reported here but have been previously published, with a profile consistent with that of UPA UC clinical trials.3 Conclusion In this interim analysis of the PROFUNDUS study, most patients with moderate-to-severe UC who initiated maintenance therapy with UPA30 were on this dosage at wk 26, reflecting high persistence in RW practice; these data suggest that UPA maintenance therapy may facilitate reductions in CS dependency over time. References: 1. AbbVie Inc. RINVOQ (upadacitinib) package insert US Food and Drug Administration. Revised May 2023. 2. AbbVie Inc. RINVOQ (upadacitinib). Summary of Product Characteristics. European Medicines Agency. Revised Feb 2025. 3. Danese S, et al. Lancet. 2022;399:2113–28. 4. Panaccione R, et al. UEG Journal 2025;13. Abstract MP781. Conflict of interest: Parkes, Gareth: Dr. Gareth Parkes reports personal payments, honoraria, speaker fees, travel grants and/or fellowships from AbbVie, Allergan, Bristol Myers Squibb, Celltrion, Ferring, Galapagos, Janssen, Napp, Takeda, and Tillotts, and directorship and shareholding with Ampersand Health. Dr. Parkes reports personal grants from AbbVie personal consulting fees from AbbVie, Arena, Aslan, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, GlaxoSmithKline, Heptares, LabGenius, Janssen, Monte Rosa, MSD, Mylan, Novartis, Numab, Pfizer, Roche, Sandoz, Takeda, UCB, and XAP membership of the ECCO Scientific Committee, and membership in the UEG Scientific Committee director of Endoread. Fumery, Mathurin: Dr. Matherin Fumery has received grants from Pfizer personal fees from AbbVie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, and Arena and non-financial support from Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, and Pfizer. Bettenworth, Dominik: Dr. Dominc Bettenworth is on the advisory board or consultant for AbbVie, Amgen, Arena, Atheneum, BNG Service GmbH, Bristol Myers Squibb, CED-Service GmbH, Celltrion, Doctorflix, DGVS, Diaplan, Else Kröner-Fresenius Foundation, Falk Foundation, Galapagos, Guidepoint, Impulze, Ferring, Janssen Cilag, Lilly, Medical Tribune, MedTriX, MSD, Mylan, Onkowissen, Pharmacosmos, Pfizer, Roche, Sandoz, Takeda, Tetrameros, Thieme, Tillotts Pharma, UCB Biopiharma, Viatris and Vifor Pharma. Armuzzi, Alessandro: Dr. Alessandro Armuzzi has received consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda. Morisset, Pierre: Dr. Pierre Morriset is an AbbVie employee and may own stock and/or stock options. Mallick, Madhuja: Dr. Madhuja Mallick is an AbbVie employee and may own stock and/or stock options. Shirley H., Chen: Dr. Shirley Chen is an AbbVie employee and may own stock and/or stock options. Kim, Jae: Dr. Jae Rok Kim is an employee of AbbVie and may own stock and/or stock options. 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.