OBJECTIVES:The objective of this study was to analyze the safety of long-term infliximab treatment, with without concomitant immunomodulators, across Crohn's disease (CD) and ulcerative colitis (UC) clinical trials.METHODS:To maximize sample size, we pooled primary safety data across 10 CD or UC trials, including five randomized, controlled trials contributing data from patients who received intravenous infliximab 5 or 10mg kg (no1,713; ±azathioprine) or placebo (n406; ±azathioprine). Pooled incidences and 95 confidence intervals (CIs) were determined for mortality, infection, and malignancy. Standardized incidence ratios and 95 CIs were also determined for malignancies using the Surveillance, Epidemiology, and End Results database.RESULTS:We observed no increase in infections, serious infections, or malignancy with infliximab vs. placebo in these patients with inflammatory bowel disease (IBD). In patients with UC, but not CD, immunomodulator treatment (vs. treatment without immunomodulator) yielded a higher incidence (95 CI) of infections (120.07 (110.66, 130.08) 100 patient-years (pt-yrs) vs. 92.47 (84.54, 100.94) 100 pt-yrs). Among placebo-treated patients with CD, but not UC, those with immunomodulator use demonstrated a higher incidence (95 CI) of malignancy vs. no immunomodulator treatment (1.84 (0.22, 6.66) 100 pt-yrs vs. 0.00 (0.00, 0.00) 100 pt-yrs). Mortality and infection-related mortality appeared unaffected by infliximab or immunomodulator treatment.CONCLUSIONS:Infliximab treatment of IBD did not appear to affect incidences of infection, mortality, or malignancy. Relative to patients with no immunomodulator use, immunomodulator-treated UC patients demonstrated a higher incidence of infection and immunomodulator-plus- placebo-treated CD patients demonstrated a higher incidence of malignancy.