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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. (Inflamm Bowel Dis 2011;)

Background: Treatment with infliximab (IFX) can result in immunogenicity through the formation of human anti-chimeric antibodies (HACAs). These antibodies are associated with a decreased duration of response, whereas therapeutic levels of IFX are associated with durable clinical response. We evaluated the clinical utility of measuring serum IFX and HACA levels. Methods: We retrospectively reviewed charts of patients with inflammatory bowel disease who had IFX drug and HACA levels measured over a three-year period from 2005-2008. The clinical utility of these tests was assessed by determining whether the result affected clinical management. The management and subsequent clinical response to therapeutic changes based on test results was evaluated. Fisher's exact test and log-rank test for discontinuation were used for statistical analysis. Results: One hundred and fifty-five patients underwent IFX level and HACA status testing. The median time to initial testing after IFX initiation was 50 weeks (IQR: 22.7-120). The main indications for testing were: loss of response to IFX (50.3%), partial response after initiation of IFX (22.6%) and possible autoimmune/delayed hypersensitivity reaction (14.8%). HACAs were identified in 35 patients (22.6%) and therapeutic IFX levels were found in 51 (32.9%). Of 177 total tests assessed, the results impacted treatment decisions in 73.4% (95% CI: 66-80%). In those with positive HACAs, change to another anti-TNF was associated with a complete or partial response in 91.6% of patients whereas increasing the dose had a response of 16.7% (p