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.