Long-term Drug Persistence and Clinical Outcomes of Ustekinumab in Crohn's Disease: A Multicenter Real-World Study from the Hokkaido Phoenix Cohort

Background Although ustekinumab (UST) is effective in Crohn’s disease (CD), long-term real-world data beyond 5 years and its effects on extraintestinal manifestations remain limited. We evaluated UST’s long-term effectiveness and safety in CD. Methods This multicenter retrospective study enrolled 317 CD patients who initiated UST between May 2017 and February 2023 at seven institutions in Japan. The primary outcome was the UST continuation rate. The secondary outcomes included factors affecting the continuation rates, surgery-free survival, endoscopic remission rates, improvement in perianal and extraintestinal manifestations, and adverse events. Results UST continuation rates at 1, 3, and 5 years were 87.6%, 69.6%, and 66.8%, respectively, with 43 patients followed beyond 5 years (maximum 6.1 years). Multivariate analysis identified week-8 albumin ≥3.3 g/dL (HR 0.30; 95%CI 0.12–0.72; p = 0.007) and week-8 C-reactive protein (CRP) ≥0.33 mg/dL (HR 2.05; 95%CI 1.14–3.69; p = 0.016) as independent predictors of continuation. Endoscopic remission rates improved significantly from baseline (10%) to week 52 (19%, p < 0.01) and week 104 (30%, p < 0.01). Among perianal fistula cases (n = 60), 28% achieved clinical fistula remission and 37% showed improvement. Resolution or improvement was observed in 76% of arthritis and 86% of psoriasis-like lesion cases. The surgery-free survival rate at 5 years was 85.1%. The adverse event rate was 10.7%. Conclusions UST demonstrated favorable medium- to long-term effectiveness and safety in CD patients with limited follow-up data beyond 5 years. Week-8 albumin and CRP levels may serve as early predictive biomarkers but require external validation in independent cohorts.