EP136 - The Ustekinumab-Surgery Synergy: Achieving Short-Term Anal Fistula Clinical and MRI Healing in Crohn's Disease

Purpose/Background: The primary objective of this study was to evaluate the short-term clinical efficacy of ustekinumab (UST) in combination with surgical intervention among patients with perianal fistulizing Crohn's disease (pfCD), and to identify potential risk factors associated with magnetic resonance imaging (MRI)-assessed healing outcomes.

Methods/Interventions: A retrospective cohort study was conducted between July 2021 and March 2025. Eligible participants included patients diagnosed with pfCD who received UST therapy alongside surgical management and completed a 24-week follow-up period. Clinical data and characteristics of perianal fistulas were systematically collected and reviewed. The primary efficacy endpoints were the rates of clinical remission and MRI-defined healing at the conclusion of treatment. Secondary outcomes encompassed changes in the Crohn's Disease Activity Index (CDAI), Perianal Disease Activity Index (PDAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and fecal calprotectin (FC) levels. Disease status was evaluated using the Simplified Endoscopic Score for Crohn's Disease (SES-CD), Van Assche MRI score, and Wexner Incontinence Score, both before and after treatment. Multivariate logistic regression analysis was performed to determine independent predictors significantly associated with MRI-based healing outcomes.

Results/Outcomes: A total of 91 patients were included in the analysis. According to the Montreal classification, 5 patients (5.5%) were classified as A1, 77 patients (84.6%) as A2, and 9 patients (9.9%) as A3. With respect to disease location, 29 patients (31.9%) were categorized as L1, 16 patients (17.6%) as L2, and 46 patients (50.5%) as L3. In terms of disease behavior, 67 patients (73.6%) exhibited B1 phenotype, 23 patients (25.3%) B2, and 1 patient (1.1%) B3. Regarding fistula complexity, 11 patients (12.1%) had simple anal fistulas, while 80 patients (87.9%) presented with complex anal fistulas. Surgical interventions included fistulotomy (76.9%), transanal opening of the intersphincteric space (TROPIS, 14.3%), video-assisted anal fistula treatment (VAAFT, 23.5%), fistula laser closure (FiLaC, 8.8%), and mucosal advancement flap (MAF, 1.1%). At the 24-week follow-up, the clinical healing rate was 89.0% (81/91). The median time to healing was 8 weeks, with an interquartile range (IQR) of 3 weeks. The MRI-defined healing rate was 72.8% (59/81). Compared with baseline values, patients demonstrated significant reductions in CDAI and PDAI scores, CRP, ESR, FC levels, Van Assche score, SES-CD, and Wexner Incontinence Score at week 24 (all P < 0.001). Anorectal manometry results showed functional improvement, with statistically significant increases in anal resting pressure (ARP), maximum anal contraction pressure (AMCP), and maximum anal squeeze duration (MASD) (all P < 0.05). Notably, no cases of de novo fecal incontinence were reported during the follow-up period. Multivariate logistic regression analysis revealed that elevated ESR (OR = 0.963, P = 0.013) and higher baseline Van Assche score (OR = 0.878, P = 0.023) were independent predictors associated with reduced likelihood of MRI healing in patients with pfCD.

Conclusion/Discussion: The combination of UST and surgical intervention demonstrates favorable short-term clinical efficacy and a favorable safety profile in the management of patients with pfCD. ESR and higher baseline Van Assche score are independent predictors associated with incomplete MRI-defined healing.

Fig.1 Clinical parameters and risk factors contribute to incomplete MRI healing
Fig.2 Case Presentations with MRI-Confirmed Healing