Summary Background The management of Crohn's disease patients with perianal lesions and anti‐TNF failure is challenging. Aims To assess the effectiveness of vedolizumab in perianal Crohn's disease and the predictors of success in a real‐life cohort. Methods We conducted a nationwide multicentre cohort study in patients with perianal Crohn's disease who received vedolizumab. In patients with active perianal Crohn's disease, the success of vedolizumab was defined by clinical success (no draining fistula at clinical examination and no anal ulcers for primary lesions) at 6 months without medical or surgical treatment for perianal Crohn's disease. Logistic regression analyses were performed to identify predictors of success. In patients with inactive perianal Crohn's disease, recurrence was defined by the occurrence of lesions and/or the need for medical or surgical treatments. Results One hundred and fifty‐one patients were included. Among them 102 patients had active perianal disease, 33 (32.4%) males, mean age 39.8 years, mean Crohn's disease duration 14.6 years; 101 (99%) had received at least one anti‐TNF. The median follow‐up time was 52 weeks. Sixty‐eight per cent of patients discontinued therapy after a median time of 33 weeks. Vedolizumab success was reached in 23/102 (22.5%). Among patients with setons at initiation, 9/61(15%) had a successful removal. In multivariable analysis, factors associated with success were the number of prior biologic agents (≥3, odds ratio, OR: 0.20, 95% CI 0.04‐0.98) and no antibiotics at initiation (OR: 4.76, 95% CI 1.25‐18.19). In 49 patients with inactive perianal Crohn's disease, perianal disease recurred in 15/49 (30.6%), 11/49 (22.4%) needed dedicated treatments. Median time to recurrence was 22 weeks. Conclusions We identified a low rate of success of vedolizumab in patients with active perianal Crohn's disease, and nearly one third of patients with inactive perianal Crohn's disease had perianal recurrence. Further evaluation is warranted in prospective studies.

INTRODUCTION: New therapeutic options for patients with Crohn's disease (CD) with perianal lesions failing anti–tumor necrosis factor (TNF) agents are needed. We aimed to assess the effectiveness of ustekinumab in perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort. METHODS: We conducted a national multicenter retrospective cohort study in patients with either active or inactive pCD who received ustekinumab. In patients with active pCD at treatment initiation, the success of ustekinumab was defined by clinical success at 6 months assessed by the physician's judgment without additional medical or surgical treatment for pCD. Univariate and multivariable logistic regression analyses were performed to identify predictors of success. In patients with inactive pCD at ustekinumab initiation, the pCD recurrence-free survival was calculated using the Kaplan-Meier method. RESULTS: Two hundred seven patients were included, the mean age was 37.7 years, the mean duration of CD was 14.3 years, and the mean number of prior perianal surgeries was 2.8. Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab. The median follow-up time was 48 weeks; 56/207 (27%) patients discontinued therapy after a median time of 43 weeks. In patients with active pCD, success was reached in 57/148 (38.5%) patients. Among patients with setons at initiation, 29/88 (33%) had a successful removal. The absence of optimization was associated with treatment success (P = 0.044, odds ratio 2.74; 95% confidence interval: 0.96–7.82). In multivariable analysis, the number of prior anti-TNF agents (≥3) was borderline significant (P = 0.056, odds ratio 0.4; 95% confidence interval: 0.15–1.08). In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively. DISCUSSION: Ustekinumab appears as a potential effective therapeutic option in perianal refractory CD. Further prospective studies are warranted.