P0621 Effectiveness and Safety of Induction Therapy with Upadacitinib for the Treatment of Perianal Crohn’s Disease : Real-World Data from a GETAID Multicentre Cohort Study

Abstract Background Upadacitinib has demonstrated efficacy as an induction treatment for Crohn’s disease (CD)1, and a post hoc analysis of phase 3 randomized, placebo-controlled trials has shown its efficacy in perianal fistulizing CD (pCD)2. However, real-world data in this setting remain limited. Methods From September 2022 to September 2024, all consecutive patients with CD treated with once-daily upadacitinib 45 mg in 32 French and Belgian GETAID centres were retrospectively included. Clinical remission (absence of draining pus including with pressure for fistulas and no anal ulcers for primary lesions, as per local physician’s judgement, with no need for new dedicated medical treatment for perianal lesions (antibiotics and/or topics), or surgical treatment) and clinical response (an improvement of at least 50% of ulcers or fistulas by physician’s assessment) were assessed at week 12. Univariate and multivariable analyses were performed to identify predictors of clinical response. Results Among the 243 patients treated, 54 (22.2%) had active perianal Crohn’s disease (pCD) at the time of induction. This group included 43 patients (81.0%) with fistulizing disease and 11 (19.0%) with isolated anal ulcers. Median age was 38 (IQR, 29.0-45.8) years, 28 (51.9%) were men, and 9 (17.0%) were active smokers. All had been previously exposed to at least one advanced therapy (median number: 4, IQR [3-5]), and 25 (47.2%) had undergone prior perianal surgery (Table 1). By week 12, clinical response was achieved in 37 patients (68.5%, n=37/54), and clinical remission in 10 patients (n=10/54, 18.5%). Among patients with fistulizing pCD, 29 patients (67.4%, n=29/43) achieved clinical response, while 6 (14.0%, n=6/43) achieved remission. Among patients with primary perianal CD, complete remission of ulcers was observed in 4 (n=4/11, 36.4%) (Figure 1). In multivariate analysis, penetrating phenotype (OR=14.8, 95%CI: 1.6-381.9, p=0.04) was associated with higher rates of clinical response at W12 while the number of prior biologics did not influence clinical response (OR = 1.63, 95% CI: 0.47-5.79; p = 0.47). Fifteen adverse events (AEs) occurred in 13 (24.1%) patients, including 5 (9.3%) serious AEs, all 5 cases corresponding to CD exacerbation. At week 12, 7 (13%) patients discontinued upadacitinib, all due to lack of efficacy. Conclusion In this real-world cohort of highly refractory CD patients, upadacitinib induction resulted in a clinical response of perianal CD in two-third of patients. 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. doi:10.1056/NEJMoa2212728 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). doi:10.1016/j.cgh.2024.08.032