P0785 One-Year Efficacy of Upadacitinib in Perianal Crohn’s Disease: A Multicenter Cohort Study.

Abstract Background Upadacitinib has demonstrated efficacy for induction and maintenance therapy in luminal Crohn’s disease (CD) (1). According to a post-hoc analysis of a phase 3 randomized controlled trial, upadacitinib also showed benefit in the treatment of fistulizing perianal CD (2). However, its real-world effectiveness in this specific phenotype has not yet been evaluated. Methods All consecutive patients with active perianal CD (primary and/or secondary lesions) treated with upadacitinib across 13 French centres between September 2022 and August 2025 were included in a retrospective cohort study. Clinical remission was defined as the absence of draining pus including with pressure and healing of anal ulcers and/or fissures, without the addition of new dedicated treatment for perianal lesions (antibiotics and/or topics). Clinical response was defined as improvement of at least 50% of fistulas and/or ulcers by physician’s assessment. MRI-based response and remission were also assessed. Treatment failure was defined as upadacitinib discontinuation, initiation of a new advanced therapy, or need for additional perianal surgery. Patients lost to follow-up were considered as treatment failures. Results Fifty-nine patients were included: 43/59 (73%) with fistulizing perianal CD and 16/59 (27%) with isolated primary anal ulcerations. Median age was 38 years (interquartile range [29–47]); 29 (49%) were male and 11 (19%) were active smokers. All patients had previously been exposed to at least two biologics (median 4 [3–5]), and 40 (68%) had a history of perianal surgery, including 34/43 (79%) in the fistulizing subgroup. Among patients with fistulizing perianal CD, clinical remission was achieved in 5/43 (12%), 11/43 (26%), and 11/43 (26%) patients at 3, 6, and 12 months, respectively, while clinical response was observed in 27/43 (63%), 21/43 (49%), and 13/43 (30%) patients (Figure 1). At 12 months, MRI response was documented in 9/14 (64%) and MRI remission in 1/14 (7%) patients with fistulizing perianal CD. Among those with isolated anal ulcerations, complete ulcer healing was observed in 4/16 (25%) at 12 months (Figure 1). No clinical or demographic factors were associated with clinical remission at 12 months in univariate analysis. Sixteen adverse events (AEs) were reported in 14 patients (27%), including three (5%) serious AEs corresponding to CD exacerbations. At 12 months, 10 patients (17%) underwent perianal drainage surgery, and 16 (27%) discontinued upadacitinib, all due to lack of efficacy. Conclusion In this real-world multicentre cohort of patients with refractory perianal CD, treatment with upadacitinib achieved clinical remission in approximately one-quarter of patients at one year. 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. (2) Colombel JF, Lacerda AP, Irving PM, et al. Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn’s Disease: A Post Hoc Analysis of 3 Phase 3 Trials. Clin Gastroenterol Hepatol. 2024;0(0). Conflict of interest: Dr. 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 Nachury, Maria: Abbvie, Alfa Sigma, Biosynex, Celltrion, Galapagos, Janssen, Lilly, MSD, Pfizer, Takeda Laharie, David: Personal Fees: Board, consulting and lecture fees from Abbvie, Alfasigma, Amgen, Biocon, Celltrion, Ferring, Fresenius-Kabi, Johnson & Johnson, Lilly, MSD, Pfizer, Sandoz and Takeda Nancey, Stéphane: board membership and lecturing fees from Abbvie, Takeda, Celltrion Healthcare, Pfizer, Galapagos, Johnson & Jonshon, Lilly, Fresenius, Amgen, Medac, MSD. Coffin, Benoît: No conflict of interest Pelletier, Anne-Laure: •ALP has received lecture/consultant fees from Janssen, Pfizer, and Novartis. Uzzan, Mathieu: Grant: ECCO-IOIBD, Fondation pour la Recherche Medicale (FRM), SNFGE Personal Fees: Abbvie, Takeda, Celltrion, Janssen, Amgen, Alfasigma, Pfizer Amiot, Aurelien: Personal Fees: Abbvie, Fresenius-Kabi, Adacyte, Tillotts pharma, Janssen, Pfizer, Biogen, AMgen, Sandoz, Takeda, Galapagos, Eli Lilly Amil, Morgane: No conflict of interest 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. 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. Bozon, Anne: No conflict of interest