Comparison of Ustekinumab and Vedolizumab Effectiveness in Perianal Crohn’s Disease

Abstract

BACKGROUND: Perianal Crohn's disease (PCD) is a severe and disabling phenotype of Crohn's disease that often requires multidisciplinary medical and surgical management. Although ustekinumab (UST) and vedolizumab (VDZ) are widely used after antitumor necrosis factor (anti-TNF) failure, direct comparative data specifically in PCD remain limited. METHODS: We conducted a multicenter, retrospective cohort study using the TriNetX US Collaborative Network to compare the effectiveness of UST versus VDZ in adults (18 y or older) with PCD between January 2017 and May 2023. Outcomes were perianal-specific clinical events, including definitive fistula surgery, incision and drainage, diversion procedures, and antibiotic use (metronidazole or ciprofloxacin), assessed at 1 and 2 years after biological initiation. Propensity score matching (PSM) (1:1) was performed to balance baseline variables. Time-to-event analyses were conducted in the matched population using Kaplan-Meier methods, and hazard ratios (HRs) were estimated using Cox proportional hazards models within the matched cohorts. RESULTS: A total of 2936 patients were identified before PSM: 1997 patients in the UST group and 939 patients in the VDZ group. After PSM, 936 patients were included in each cohort. In the matched cohorts, UST was associated with significantly lower risk of definitive perianal fistula surgery (HR: 0.66, 95% CI: 0.50-0.89; P<0.01), and composite surgical events (HR: 0.70, 95% CI: 0.54-0.87; P<0.01) compared with VDZ at 1 year. Rates of antibiotic use, incision and drainage of perianal abscess, and diversion procedures were numerically lower but not statistically significant. At 2 years, these findings persisted, with significantly lower cumulative incidence of definitive perianal fistula surgery (HR: 0.78, 95% CI: 0.61-0.90; P=0.03), composite surgical events (HR: 0.81, 95% CI: 0.69-0.90; P<0.01), and antibiotic use (HR: 0.86, 95% CI: 0.75-0.93; P=0.04) in the UST cohort compared with VDZ. Rates of incision and drainage and diversion procedures remained similar between groups. CONCLUSION: In this large real-world cohort, UST was associated with lower risks of perianal surgical interventions at one and two years and reduced antibiotic utilization at two years compared with VDZ in patients with PCD. These findings highlight meaningful differences in real-world effectiveness between therapies and support the need for prospective studies to further evaluate comparative effectiveness in this population.