DOP029 One-Year Effectiveness and Safety of Upadacitinib in 261 Patients With Crohn’s Disease: A Multicenter Real-World Cohort Study.

Abstract Background Upadacitinib has demonstrated efficacy as a maintenance therapy for Crohn’s disease (CD) in a randomized, placebo-controlled phase 3 clinical trial (1). However, real-world data beyond the induction phase remain limited. Methods All consecutive patients with refractory CD starting upadacitinib 45 mg/day across 25 French centres between September 2022 and August 2024 were included in this retrospective cohort. The primary endpoint was steroid-free clinical remission (SFCR) at 12 months, defined as a Harvey–Bradshaw Index (HBI) < 4, using both as-observed (AO) and nonresponder-imputation (NRI) analyses. Secondary endpoints included clinical response (HBI decrease ≥ 3 points and/or HBI < 4), clinical remission, biological remission (fecal calprotectin ≤ 250 µg/g or CRP ≤ 5 mg/L when calprotectin was unavailable), using AO and NRI analyses. Endoscopic or radiologic response/remission (bowel ultrasound and/or MRI) were reported AO. Safety was assessed in all patients. Results Among the 261 included patients, median age was 38 years (IQR 29–47), 128 (49%) were male, and 27 (10%) had a stoma. All had previously received at least one biologic therapy (median 4, IQR [3–4]), and 132 (51%) had undergone intestinal resection. At 12 months, the proportions of patients achieving SFCR were 57/179 (32%) AO and 57/234 (24%) after NRI (Figure 1). At 12 monthsradiologic response in 21/67 (31%), and radiologic remission in 9/67 (13%). Endoscopic response and remission were achieved in 18/40 (45%) and 16/47 (34%) patients, respectively. Among the 225/261 (86%) patients continuing upadacitinib beyond the 12-week induction phase, 151/225 (67%) did not require re-induction, while 54/225 (24%) and 20/225 (9%) received one or two re-induction courses (45 mg/day) between months 3 and 12. At 12 months, among patients with spondyloarthritis, 5/28 (18%) achieved clinical remission for axial involvement, and 5/28 (18%) for peripheral involvement. In multivariate analysis, a body mass index < 18.5 kg/m² (OR 0.21, 95% CI 0.05–0.72, p = 0.02), prior intestinal resection (OR 0.34, 95% CI 0.16–0.71, p = 0.005), and an HBI > 7 (OR 0.47, 95% CI 0.24–0.94, p = 0.03) were associated with lower SFCR rates. A total of 125 adverse events were reported in 97 patients (37%), including 27 serious events: 24 CD exacerbations, one septic arthritis, one intestinal failure and one EBV-associated colonic lymphoproliferation. Acne occurred in 43 patients (17%), leading to treatment discontinuation in 5 (2%). Two cases of herpes zoster (1%) were reported. Conclusion In this real-world cohort of multi-refractory CD patients treated with upadacitinib, between one-quarter and one-third achieved SFCR after one year of treatment. References: (1)Loftus EV, Panés J, Lacerda AP, et al. Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med. 2023;388(21):1966-1980. Conflict of interest: Richard, Nicolas: Lecture/consultant fees from AbbVie, Amgen, Celltrion, Ferring, Janssen, Lilly, Sandoz and Takeda. Seksik, Philippe: I received personal fees from Takeda, Janssen, Merck MSD, Biocodex, Ferring, Fresenius Kabi, Astellas, Amgen, Pfizer, Pilege and Abbvie Altwegg, Romain: Advisory boards from Abbvie, Takeda, Johnson and Johnson, Lilly, Alphasigma, Celltrion, Pfizer, Amgen, Biogen, Sandoz, Ferring Amiot, Aurelien: A.A. received consulting fees from Abbvie, Lilly, MSD, Pfizer, Takeda, Tillotts Pharma, Adacyte, Janssen and Sandoz as well as lecture fees and travel accommodations from Abbvie, Lilly, Janssen, Pfizer, Takeda, Biogen, Fresenius Kabi, Adacyte, Amgen and Celltrion. Vuitton, Lucine: LV has received fees for lectures and/or consulting fees from Abbvie, Amgen, Johnson & Johnson, Celltrion, Takeda, Pfizer, Lilly, Ferring, MSD, Dr Falk Pharma, Nordic Pharma, Alpha sigma. Nachury, Maria: MN received board membership, consultancy, or lecture fees from Abbvie, Amgen, Biogen, Celltrion, Ferring, Fresenius-Kabi, Galapagos, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Pfizer, Takeda, and Viatris. Bouguen, Guillaume: GB received lecture/consultant fees from Abbvie, Adacyte, Amgen, Celltrion, Edimark, Ferring, Fresinus Kabi, Galapagos, Janssen, Lilly, Pfizer, Sandoz, Takeda, and Tillots. Gilletta de Saint Joseph, Cyrielle: CG has received lecture/consultant fees from AbbVie, AlfaSigma, Amgen, Celltrion, Janssen, Lilly, MSD, Pfizer and Takeda. Coffin, Benoît: No conflict of interest Buisson, Anthony: Anthony Buisson: Consulting fees from Abbvie, Amgen, Arena, Biogen, Celltrion Healthcare, CTMA, Galapagos/AlfaSigma, GutyCare/Resilience Janssen, Lilly, MSD, Nexbiome, Pfizer, Roche, Sandoz, Takeda and Tillotts. Lecture fees from Abbvie, Amgen, Biogen, Celltrion Healthcare Galapagos/AlfaSigma, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Norgine, Pfizer, Roche, Takeda, Tillotts and Vifor Pharma. Research grant from Abbvie, Celltrion Healthcare, Janssen, Lessaffre, Lilly, Pfizer, Sandoz and Takeda. Peyrin-Biroulet, Laurent: LPB has received lecture/consultant fees from Abbvie, Abivax, Adacyte, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, BMS, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par’ Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx, and Ysopia. LPB has received grants from Celltrion, Fresenius Kabi, Medac, MSD, and Takeda. Pelletier, Anne-Laure: ALP has received lecture/consultant fees from Janssen, Pfizer, and Novartis. Nancey, Stéphane: SN has received lecture/consultant fees from AbbVie, Ferring, Tillotts, Amgen, Fresenius, Sandoz, Pfizer, Celltrion, Gilead, Galapagos, Janssen, and Takeda. Rouillon, Clea: CR has received lecture/consultant fees from Abbvie, Lilly, Janssen, Biogen, Amgen, Takeda and Galapagos. Le Berre, Catherine: CLB has served as a consultant for Abbvie, Celltrion, Janssen, Gilead and Takeda has received payment for lectures from Abbvie, Amgen, Celltrion, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Nordic Pharma, Pfizer, and Takeda has received meeting support fees from Abbvie, Celltrion, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Pfizer, Sandoz, and Takeda. Allez, Matthieu: No conflict of interest Uzzan, Mathieu: No conflict of interest Caillo, Ludovic: LC has received lecture/consultant fees from AbbVie, Celltrion, Biogen, Amgen, Sandoz, Pfizer, Alfasigma, Lilly, Janssen, and Takeda. Vidon, Mathias: No conflict of interest Goutorbe, Félix: No conflict of interest Amil, Morgane: No conflict of interest Brixi-Benmansour, Hedia: HB received consulting fees from Abbvie, Takeda, Janssen as well as lecture fees and travel accommodations from Abbvie, Janssen, Pfizer, Takeda, and Celltrion. Sickersen, Gaelle: No conflict of interest Laharie, David: DL declares counseling, boards, transports or fees from Abbvie, Amgen, Biogaran, Biogen, Celltrion, Ferring, Galapagos, Janssen, Lilly, Medac, MSD, Pfizer, Prometheus, Takeda, and Theradiag. Fumery, Mathurin: M.F. has received lecture/consultant fees from AbbVie, Ferring, Tillotts, MSD, Biogen, Amgen, Fresenius, Hospira, Sandoz, Pfizer, Celgene, Gilead, Boehringer, Galapagos, Janssen, and Takeda. N.R. has received lecture/consultant fees from AbbVie, Janssen and Takeda.