Combining infliximab with 6-mercaptopurine/azathioprine for fistula therapy in Crohn's disease.

Abstract

Fistulas occur in about one third of patients with Crohn's disease and rarely heal spontaneously. Conventional medical and surgical therapy often fails. The anti-TNF-alpha antibody infliximab offers a novel therapeutic option. By this approach, closure of fistulas was reported in 45% of cases. However, after discontinuation of therapy, most fistulas recurred. Azathioprine and 6-mercaptopurine (6-MP) are effective drugs in Crohn's disease and lead to closure of fistulas in 30-40% of cases. Thus, the aim of this study was to evaluate the combination of infliximab with 6-mercaptopurine/azathioprine as therapy for fistulas in patients with Crohn's disease. A total of 16 patients (mean age 37 yr) with Crohn's fistulas resistant to conventional measures were treated with a combination of three or four infusions of infliximab and long term 6-MP/azathioprine. In all, 13 patients had perianal fistulas, two had abdominal fistulas, and one patient had both perianal and recto-vaginal fistulas. Therapy success was defined as complete closure of fistulas for a minimum observation period of 6 months after fistula closure. In 12 (75%) of the 16 patients, we observed complete closure of the fistulas that persisted for >6 months (median follow-up 10 months, range 6-11 months). The median time to complete closure of fistulas was 14 days (range 2-36 days). In four patients, therapy success was not achieved. Our pilot study reveals that concomitant and long term 6-MP/azathioprine therapy could prolong the effect of an initial infliximab therapy on fistula closure in patients with Crohn's disease. These data prompt larger controlled trials.