Gut 53:780-782 doi:10.1136/gut.2003.020552
  • Commentary

Balancing the risks and benefits of infliximab in the treatment of inflammatory bowel disease

  1. W J Sandborn,
  2. E V Loftus
  1. Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA
  1. Correspondence to:
    Dr W J Sandborn
    Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA;

    Patients with moderate to severely active Crohn’s disease treated with infliximab may have a small but real risk of developing severe infections, opportunistic infections, and non-Hodgkin’s lymphoma

    Infliximab, a monoclonal antibody to tumour necrosis factor (TNF) α, is an important advance in the treatment of Crohn’s disease.1–5 The efficacy of infliximab for the treatment of ulcerative colitis is still unclear.6,7 Infliximab was approved for the treatment of Crohn’s disease in 1998 based on a 12 week phase 2 trial in 108 patients1 (followed by a 36 week extension trial)3 and a small phase 3 trial in 94 patients,2 both of which showed compelling efficacy. Because of the possibility of open label crossover at week 4, 102 of 108 patients in the phase 2 trial received infliximab by week 12. Thus only six patients in the phase 2 study and 31 patients in the phase 3 study who received placebo were available for safety follow up without crossover to infliximab. Although not all patients enrolled in these studies were receiving concomitant corticosteroids and/or azathioprine or 6-mercaptopurine, regulatory approval in the USA was granted only in patients with moderate to severely active Crohn’s disease unresponsive to conventional therapy (not defined) and for fistulising Crohn’s disease; and in Europe in patients with moderate to severely active Crohn’s disease or fistulising Crohn’s disease unresponsive to a full and adequate course of corticosteroids and immunosuppressive therapy. These restrictions were, at least in part, a reflection of the uncertainties regarding safety.

    Subsequently, two blinded, placebo controlled, phase 4 maintenance trials (designed as infliximab withdrawal trials) were conducted in 573 patients with moderate to severely active Crohn’s disease4 and in 306 patients with fistulising Crohn’s disease.5 All patients in these two maintenance studies initially received at least one …