P0893From healing to functional protection: Long-term superior outcomes of surgical intervention combined with Ustekinumab in perianal fistulizing Crohn’s Disease

Background Current studies focus on the short-term efficacy of ustekinumab (UST) in perianal fistulizing Crohn’s disease (pfCD), but lack evaluations of fistula healing-related risk factors, long-term surgical efficacy, and safety in this population [1, 2]. This study aims to assess the long-term clinical efficacy and safety of UST combined with surgery for pfCD and identify risk factors and trough drug concentrations associated with magnetic resonance imaging (MRI)-assessed healing outcomes. Methods A retrospective cohort study was conducted from July 2021 to May 2025. The primary efficacy endpoint was the rate of MRI-defined healing at the conclusion of the follow-up period. Secondary outcomes included changes in the Crohn’s Disease Activity Index (CDAI), Perianal Disease Activity Index (PDAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC) levels, Simplified Endoscopic Score for Crohn’s Disease (SES-CD), Van Assche MRI score, Wexner Incontinence Score, and anorectal manometry. Results A total of 106 patients were included in the analysis. The median healing time was 8 weeks (IQR, 2 weeks). At the 52-week follow-up, the MRI healing rate was 90.1% (73/81). At the 104-week follow-up, five patients experienced perianal fistula recurrence (5/50, 10%). All recurrent patients achieved clinical healing after reoperation. Forty-nine patients (49/50, 98%) achieved MRI healing at the 104-week follow-up. Significant reductions were observed in CDAI, PDAI, CRP, ESR, FC levels, Van Assche score, and SES-CD at week 52 (all P < 0.05). Anorectal manometry demonstrated functional improvement, with significant increases in anal resting pressure (ARP) and maximum anal contraction pressure (AMCP) (both P < 0.05). No significant differences were observed in the Wexner Incontinence Score, and no episodes of fecal incontinence were reported during the follow-up period. Multivariate regression analyses indicated that baseline Van Assche score (OR = 0.811, 95% CI: 0.703-0.935) and 16-week UST trough concentration (OR = 1.162, 95% CI: 1.002-1.347) were independent predictors of MRI healing (both P < 0.05). Baseline Van Assche score, with an optimal cut-off of 15 (AUC = 0.766, sensitivity = 92.0%, specificity = 52.9%), was negatively correlated with MRI healing. Therapeutic drug monitoring identified a 16-week UST trough concentration threshold of 4.4 μg/mL (AUC = 0.707, sensitivity = 72.9%, specificity = 66.7%). Conclusion Surgical intervention combined with UST demonstrates favorable long-term clinical efficacy and safety in patients with pfCD, with high rates of radiological fistula closure. Baseline Van Assche score < 15 and UST trough concentration > 4.4 μg/mL at week 16 are positive predictors of MRI-defined healing. References: [1] Yao J, Zhang H, Su T, Peng X, Zhao J, Liu T, Wang W, Hu P, Zhi M, Zhang M. Ustekinumab Promotes Radiological Fistula Healing in Perianal Fistulizing Crohn’s Disease: A Retrospective Real-World Analysis. J Clin Med. 2023 Jan 25;12(3):939. [2] Xu Simin, Yao Yibo, Li Yikun, et al. Efficacy of surgery combined with ustekinumab in active Crohn’s disease patients with perianal fistula and its influence on anal function[J]. Chinese Journal of Inflammatory Bowel Diseases (English Edition), 2025, 9(1): 59-66. Conflict of interest: Dr. Yin, Lu: No conflict of interest Weng, Feiyang: No conflict of interest Yao, Yibo: No conflict of interest wang, chen: No conflict of interest