P1073Real-World Effectiveness, Symptomatic Improvement, and Safety of Upadacitinib in Patients With Moderate-to-Severe Ulcerative Colitis: Interim Findings From the PROFUNDUS Study

Abstract Background Upadacitinib (UPA), an oral Janus kinase inhibitor (JAKi), is approved for the treatment of moderate-to-severe ulcerative colitis (UC).1,2 The Prospective Real-World Study of UPA in UC (PROFUNDUS) is an open-label, noninterventional study evaluating physician prescribing patterns and clinical endpoints among UPA-treated patients with moderate-to-severe UC in routine clinical practice (initiated 15Aug2022); this interim analysis assesses real-world (RW) clinical effectiveness, symptomatic improvement, and safety.4 Methods Patients, comprising 494 of the first 500 eligible adults (18-79 years yrs), in the full analysis set (FAS), with moderate-to-severe UC who initiated once-daily UPA across 16 countries, per investigator discretion and according to the local label; steroid tapering was not mandated and left to investigator discretion. Baseline (BL) demographics and disease characteristics were reported among FAS; endpoints assessed included clinical response per Partial Adapted Mayo score (PAMS), corticosteroid (CS)-free response per PAMS, clinical remission (CR) per Partial Mayo score, absence of abdominal pain, and absence of bowel urgency at week 26 among evaluable FAS pts and by advanced therapy (AT) status (AT-experienced vs AT-naive; cut-off date: 28Feb2025). Safety endpoints were assessed, with treatment-emergent adverse events (TEAEs) reported as counts and percentages. Results Among FAS at BL (last measurement on or before the initial UPA dose), the mean (SD) patient age was 39.4 (13.3) yrs, with 57.1% males, 21.5% on CS; mean (SD) disease duration was 7.8 (7.0) yrs, with 54.6% of patients being AT-experienced, 41.9% failed ≥1 TNF, and 14.2% failed ≥1 JAKi. At week 26, 81.8%, 72.4%, 66.3%, and 71.9% of patients achieved clinical response, CR, no abdominal pain, and no bowel urgency, respectively; among those on BL CS, 64.4% attained CS-free response (Table 1). Similar results were observed for all endpoints regardless of AT status (Table 1). Among patients treated with UPA45/UPA15, UPA45/UPA30, or any UPA dose, TEAEs were as follows: any AE, 66.0%; 50.8%; 51.4%, serious AEs, 3.8%; 4.6%; 5.7%, and severe AEs, 5.7%; 4.0%; 5.5% (Table 2). Within this overall cohort, the subgroup of patients who experienced TEAEs potentially related to UPA exhibited serious and severe AEs at 3.6%, 6.3%, 6.9%, and 7.1%, 5.4%, 6.9%, respectively (Table 2). Conclusion In the PROFUNDUS study, UPA-treated patients with UC achieved high rates of clinical and symptomatic improvement, regardless of AT status within an RW setting. Overall, UPA was well-tolerated, with few serious AEs observed, most of which were unrelated to UPA, as determined by the study investigator. 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: 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. Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Bettenworth, Dominik: 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. Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda Morisset, Pierre: Employee of AbbVie and may own stock and/or stock options. Mallick, Madhuja: Employees of AbbVie and may own stock and/or stock options. Chen, Shirley H.: Employee of AbbVie and may own stock and/or stock options. Kim, Jae: Employees of AbbVie and may own stock and/or stock options. Suravaram, Smitha: Employee of AbbVie and may own stock and/or stock options. Parkes, Gareth: 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.