Infliximab maintenance therapy for fistulizing Crohn's disease

N Engl J Med. 2004 Feb 26;350(9):876-85. doi: 10.1056/NEJMoa030815.

Abstract

Background: Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas.

Methods: We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn's disease and one or more draining abdominal or perianal fistulas of at least three months' duration. Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54. The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent randomization.

Results: The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks vs. 14 weeks, P<0.001). At week 54, 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas, as compared with 36 percent of patients in the infliximab maintenance group (P=0.009).

Conclusions: Patients with fistulizing Crohn's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Crohn Disease / complications
  • Crohn Disease / drug therapy*
  • Cutaneous Fistula / drug therapy*
  • Cutaneous Fistula / etiology
  • Double-Blind Method
  • Drug Tolerance
  • Female
  • Gastrointestinal Agents / adverse effects
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Infliximab
  • Infusions, Intravenous
  • Intestinal Fistula / drug therapy*
  • Intestinal Fistula / etiology
  • Male
  • Middle Aged
  • Rectal Fistula / drug therapy
  • Rectal Fistula / etiology
  • Recurrence
  • Remission Induction
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Gastrointestinal Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab