Combined Approach with Infliximab, Surgery, and Methotrexate in Severe Fistulizing Anoperineal Crohn's Disease: Results from a Prospective Study

Background: Infliximab is the only medical therapy that has been proven to be effective in fistulizing Crohn's disease (CD), but the recurrence rate of fistulas is high despite maintenance therapy. The aim of this prospective study was to evaluate the short- and long-term efficacy of a combined schedule with infliximab, methotrexate, and sphincter-sparing surgery in patients with severe fistulizing anoperineal CD. Methods: From January 2006 to November 2007, all consecutive patients in three referral centers with severe fistulizing anoperineal CD were prospectively included after primary drainage. At inclusion, patients received three infliximab infusions at weeks 0, 2, and 6, and maintenance therapy with methotrexate. A second optimized surgical step consisting of at least removal of setons was performed between the second and the third infliximab infusions. Results: Thirty-four CD patients (26 women; median age 38.5 years) with complex anoperineal fistula were enrolled (including 9 with recto-vaginal fistulas, and 10 with anorectal stenosis). At week 14 the response rate was 85% with 74% complete responders. At 1 year, 50% were still responders; luminal CD worsening was the major cause of relapse. Median Perineal Disease Activity Index (PDAI) and magnetic resonance imaging (MRI) scores significantly decreased from baseline to week 50. Conclusions: A combined approach with infliximab induction, two surgical sphincter-sparing steps and methotrexate is effective in achieving short- term response in severe fistulizing anoperineal CD. The best maintenance regimen remains to be determined.