Ustekinumab in the Management of Perianal Fistulizing Crohn’s Disease: Current Evidence and Practical Strategies

Perianal fistulizing Crohn’s disease (PFCD) is a severe and complex manifestation associated with high morbidity and limited treatment durability. Ustekinumab is a monoclonal antibody targeting the interleukin-12/23 pathway, which is involved in the pathogenesis of PFCD. Evidence from post hoc analyses and real-world studies has shown the therapeutic potential of ustekinumab in both anti-tumor necrosis factor-experienced and selected biologic-naïve patients with PFCD. Preliminary evidence has indicated that the treatment effect may be improved when used in combination with surgical interventions such as seton placement or sphincter-preserving procedures. Adjunctive antibiotics during induction and early monitoring of clinical and radiologic response may further enhance outcomes. While ustekinumab is increasingly being incorporated into multidisciplinary PFCD management, prospective fistula-specific trials are needed to clarify its optimal positioning. Future research should also focus on predictive biomarkers and treatment algorithms to support personalized and durable care.