Real-World Effectiveness of Upadacitinib for Perianal Crohn’s Disease: A Multicenter Retrospective Study

Background & Aims A post-hoc analyses of phase III trials showed efficacy of upadacitinib in perianal Crohn’s disease, but real-world effectiveness is scarce, and radiologic response has not been reported previously. This study evaluated clinical and radiologic outcomes of patients with perianal Crohn’s disease treated with upadacitinib. Methods In this multicenter retrospective cohort study, adults with active perianal Crohn’s disease treated with upadacitinib across 10 North American centers were included. The primary outcome was clinical response, defined as a ≥3-point reduction in the Perianal Disease Activity Index. Secondary outcomes included clinical remission (Perianal Disease Activity Index ≤4 and ≥3-point decrease or no worsening), ≥50% C-reactive protein reduction, pelvic magnetic resonance imaging outcomes (per TOpClass criteria), and rates of hospitalization, antibiotic use, and perianal Crohn’s disease–related surgery. Subgroup and Cox regression analyses assessed the effect of perianal Crohn’s disease duration, Montreal classification, prior biologic and anti–tumor necrosis factor exposure. Results Among 125 patients (56% male, median age 33 years), 48% had complex fistulas and 77.4% had prior anti–tumor necrosis factor exposure. At follow-up, 45.5% achieved clinical response, 39.4% clinical remission, 5.1% were hospitalized, and 13.1% underwent perianal surgery. On pelvic magnetic resonance imaging (n = 78), 55.1% improved and 11.5% completely healed. Clinical response was higher in anti–tumor necrosis factor-naïve patients with perianal Crohn’s disease (66.7% vs 33.3%; P = .001) and those with shorter disease duration (54.7% vs 33.3%; P = .04). Prior anti–tumor necrosis factor exposure predicted lower clinical response (hazard ratio, 0.38; 95% confidence interval, 0.22–0.66; P < .001). Conclusions Treatment with upadacitinib was associated with improved fistula outcomes in patients with perianal Crohn’s disease, with greater effectiveness in those anti–tumor necrosis factor-naïve or with shorter disease duration.