Sa1263 A Prospective Multicenter Trial Evaluating the Benefit of Initial Seton Placement Prior to Starting Anti-TNF Therapy for the Treatment of Crohn's Perianal Fistulas

Background Fistulizing disease occurs in up to 40% of patients with Crohn's disease (CD) . Symptoms, including anal pain, purulent discharge, and incontinence, are associated with high morbidity and impaired quality of life. Vedolizumab (VDZ) is a monoclonal antibody to alpha4beta7 integrin with demonstrated efficacy and safety in the treatment of patients with CD. The present exploratory analysis evaluated the efficacy of VDZ in the subpopulation of patients with fistulizing CD from a phase 3, randomized, placebo (PBO)-controlled trial (GEMINI 2).1 Methods In the GEMINI 2 study, patients who received 2 doses of VDZ during the induction phase and achieved a clinical response at week 6 received treatment with PBO or VDZ 300 mg every 8 weeks (Q8W) or every 4 weeks (Q4W) for an additional 46 weeks (maintenance intent-to-treat [ITT] population). Fistula closure, a prespecified exploratory endpoint, was assessed at each visit (2-6 week intervals) until week 52. The percentage of patients achieving fistula closure and mean time to fistula closure were calculated. Results Among the maintenance ITT population (N=461), 57 patients (12%) had 1 or more draining fistulae at study entry, with 74% of fistulae located perianally. Of these patients, 44-49% had failed prior anti-tumor necrosis factor therapy and 39-54% had prior surgery for CD. By week 14, 28% of patients treated with VDZ/VDZ (Q8W + Q4W combined) had achieved fistula closure versus 11% of those receiving VDZ/PBO (Table). This treatment difference was maintained up to week 52. Kaplan-Meier probabilities of fistula closure with VDZ treatment were 29.2% and 33.4% at 6 and 12 months, respectively; notably, the number of patients at risk was small (Figure). Conclusion In the GEMINI 2 maintenance ITT population, a greater percentage of patients with draining fistulae at study entry achieved fistula closure when they continued treatment with VDZ compared with those who were re-randomized to PBO. This effect was maintained through to week 52.These preliminary findings support the role of VDZ in the treatment of fistulizing disease and warrant further investigation in dedicated prospective studies in this population. Reference 1. Sandborn WJ, et al. N Engl J Med . 2013;369(8):711-721; NCT00783692. The clinical study was funded by Millennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.). Medical writing assistance was provided by inVentiv Medical Communications and supported by Takeda Pharmaceuticals International, Inc.