N Engl J Med  1999 May 6;340(18):1398-405 

Infliximab for the treatment of fistulas in patients with Crohn's disease.

Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA,

Podolsky DK, Sands BE, Braakman T, DeWoody KL, Schaible TF, van Deventer SJ.

Mount Sinai Medical Center, New York, NY, USA.

BACKGROUND: Enterocutaneous fistulas are a serious complication of Crohn's

disease and are difficult to treat. Infliximab, a chimeric monoclonal antibody

to tumor necrosis factor alpha, has recently been developed as a treatment for

Crohn's disease. We conducted a randomized, multicenter, double-blind,

placebo-controlled trial of infliximab for the treatment of fistulas in patients

with Crohn's disease. METHODS: The study included 94 adult patients who had

draining abdominal or perianal fistulas of at least three months' duration as a

complication of Crohn's disease. Patients were randomly assigned to receive one

of three treatments: placebo (31 patients), 5 mg of infliximab per kilogram of

body weight (31 patients), or 10 mg of infliximab per kilogram (32 patients);

all three were to be administered intravenously at weeks 0, 2, and 6. The

primary end point was a reduction of 50 percent or more from base line in the

number of draining fistulas observed at two or more consecutive study visits. A

secondary end point was the closure of all fistulas. RESULTS: Sixty-eight

percent of the patients who received 5 mg of infliximab per kilogram and 56

percent of those who received 10 mg per kilogram achieved the primary end point,

as compared with 26 percent of the patients in the placebo group (P=0.002 and

P=0.02, respectively). In addition, 55 percent of the patients assigned to

receive 5 mg of infliximab per kilogram and 38 percent of those assigned to 10

mg per kilogram had closure of all fistulas, as compared with 13 percent of the

patients assigned to placebo (P=0.001 and P=0.04, respectively). The median

length of time during which the fistulas remained closed was three months. More

than 60 percent of patients in all the groups had adverse events. For patients

treated with infliximab, the most common were headache, abscess, upper

respiratory tract infection, and fatigue. CONCLUSIONS: Infliximab is an

efficacious treatment for fistulas in patients with Crohn's disease.