Effectiveness and Safety of Advanced Dual-Targeted Therapy in Refractory Perianal Crohn's Disease

Perianal Crohn's disease (CD) remains challenging to treat despite the increasing number of advanced therapies. Advanced dual-targeted therapy has emerged as a new treatment option in CD, but no data are available for perianal CD. The aim of this study was to evaluate the effectiveness and safety of advanced dual-targeted therapy for anoperineal fistulas (APFs) in CD patients.

We prospectively included all consecutive patients receiving an advanced dual-targeted therapy for APFs from August 2019 to December 2023 in a single tertiary perianal CD centre. The primary outcome was clinical effectiveness. Secondary outcomes were patients' treatment perception, radiological effectiveness, luminal disease effectiveness, impact on extra-intestinal manifestations, and safety. Factors associated with complete clinical remission of APFs were identified using logistic regression.

A total of 33 patients were included. The most frequently used advanced dual-targeted therapy was a combination of infliximab and ustekinumab (75.8%). After a median follow-up of 27.4 months, 48.5% and 97.0% of patients were in complete clinical remission and reported a perceived improvement, respectively. Complete radiological remission was achieved in 24.2% of the patients. A concomitant improvement in luminal intestinal involvement was observed in 46.1% of cases, and in extra-digestive manifestations in 45.8% of cases. Treatment tolerance was considered good or very good in 90.9% of cases. Associated anal ulcers and long-term exposure to antibiotics were associated with a lower likelihood of complete clinical remission for fistulas.

These findings suggest that advanced dual-targeted therapy is a valid option with a good safety profile for the treatment of refractory APFs. Larger studies are required to identify the most effective combination.