P0639Real-World Effectiveness, Safety, and Dose Modifications of Upadacitinib in Patients with Crohn’s Disease: A Canadian Multicenter Study

Abstract Background Upadacitinib (UPA) is widely used for the treatment of Crohn’s disease (CD) but data on clinical outcomes after extended follow-up in daily practice remain scarce. The aim of this study was to assess the real-world effectiveness, safety, and dose modifications of UPA in patients with CD. Methods This multicenter retrospective cohort study included adults with CD initiating UPA at 7 Canadian centers (2019/10–2025/04). Patients were followed from treatment start until database lock (June 2025), discontinuation, or loss to follow-up (censored). The primary endpoint was corticosteroid-free clinical remission (CFCR; HBI 5 off systemic corticosteroids ≥90 days). Biochemical (FCP 250 µg/g and/or CRP 10 mg/L) and endoscopic (SES-CD ≤4) remission rates were captured. We documented adverse events (AEs), analyzed drug persistence by Kaplan–Meier, and evaluated predictors of CFCR by Cox regression. Results We included 296 patients (mean age 44.9 ± 15.9 years; 45.9% female) with a median follow-up of 37.7 weeks (IQR 42.4). During the maintenance phase, 24 (81.1%) patients underwent dose escalation. Prior exposure to any and ≥3 advanced therapies was noted in 93.3% (n = 276) and 39.2% (n = 116), respectively, and 28.0% (n = 83) used corticosteroids at baseline. UPA starting doses were 15 mg in 6.4% (n = 19), 30 mg in 8.4% (n = 25), and 45 mg in 84.4% (n = 249) of patients. At the end of follow-up, 55.4% (n = 164) achieved CFCR; clinical and biochemical remission rates were 60.1% (n = 178) and 44.4% (n = 131) (Table 1). Endoscopic remission occurred in 24/61 colonoscopies. There were 145 AEs reported in 104 patients, predominantly acne (n = 28), and infections (n = 29; 8 classified as serious (S)AEs). Of all AEs, 10.3% were SAEs, including thrombo-embolic events (n = 2), herpes zoster (n = 1), and malignancy (n = 1). There were 29 (9.8%) patients who experienced 40 CD-related hospitalizations, and 26 (8.8%) patients underwent 35 surgeries: 12 intestinal resections, 3 colectomies, 16 perianal, and 4 other IBD-related procedures. UPA was discontinued in 19.3% (n = 57), mainly for lack of efficacy (n = 30) or AEs (n = 13). Drug persistence at year 1 was 73.9%. None of the 10 selected clinical variables were significantly associated with CFCR on Cox regression. Conclusion In this large and refractory Canadian CD cohort with extensive prior exposure to advanced IBD therapies, a substantial proportion of patients experienced clinical benefit from UPA. Treatment persistence was high while SAEs were rare, and AEs resulted in treatment discontinuation in 5%. Conflict of interest: Dr. van Lierop, Lisa: Nothing to disclose Dang, Rebecca: Nothing to disclose Omeltchenko, Tyler: Nothing to disclose Adriaanse, Marlou: Nothing to disclose Gozdzik, Michal: M.G. has received an educational grant and speaker fees from Pfizer and participated in consultancy meetings with AbbVie, Takeda, and Celltrion. Kroeker, Karen: K.K. has received honoraria from Abbvie, Janssen, Celltrion, Pfizer, Takeda, and has acted as a consultant for the CADTH. Halloran, Brendan: Speaker/Consultant - Johnson and Johnson, Abbvie, Takeda, Pendopharm, Fujifilm, Celltrion, Shire, Pfizer Research Grants - Johnson and Johnson, Abbvie, Pfizer Wong, Karen: Abbvie - honoraria speaker / advisory board Janssen - honoraria speaker / advisory board Peerani, Farhad: Dr. Peerani has received speaker or advisory board fees from Janssen, Takeda, AbbVie, Pfizer, Ferring, and Eli Lilly. Chow, Jocelyn: Nothing to disclose McCurdy, Jeffrey: J.M. received consulting fees and or speaker honorarium from AbbVie, Bristol Myers Squibb, Fresenius Kabi, Ferring, Janssen, Takeda, and Pfizer. Narula, Neeraj: Grant: Takeda, Pfizer, Abbvie Personal Fees: Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Sandoz, Iterative Health, Innomar Strategies, Fresinius Kabi, Viatris, Celltrion, Organon, Eli Lilly, Ferring Non-financial Support: Abbvie, Janssen, Takeda, Pfizer, Ferring Siffledeen, Jesse Shaalan: I have received consulting and/or speaker fees from Johnson & Johnson, Abbvie, Takeda, Pendopharm, Fresenius Kabi, Jamp Bio, Bristol Myers Squibb, Pfizer, Celltrion, Ferring, Eli Lilly, Sanofi, Regeneron, Organon Du, Lillian: AbbVie - Consultant Organon - Consultant Pendopharm - Consultant Celltrion Healthcare - Consultant Pfizer Canada - Consultant Dang, Thucnhi: Nothing to disclose Ma, Christopher: Consulting fees: AbbVie, Alimentiv, Amgen, Anaptys Bio, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Domain Therapeutics, Eupraxia, Eli Lilly, Ferring, Forte Biosciences, Fresenius Kabi, Gilead, Janssen, McKesson, Merck, Mirador Therapeutics, Pendopharm, Pfizer, Roche, Sanofi, Takeda, Tillotts Pharma Speaker’s fees: AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma Royalties: Springer Publishing Research Support: AbbVie, Eli Lilly, Ferring, Pfizer Hoentjen, Frank: Frank Hoentjen has served on advisory boards or as speaker for Abbvie, CCRN, Janssen, Takeda, Pfizer, Celltrion, Teva, Amgen and Pendopharm, and has received independent research funding from Celltrion, Janssen, Abbvie, and Takeda.