• Crohn’s disease
• inflammatory bowel disease
• infliximab
• lymphoma
• mortality
• ulcerative colitis

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 …