title: A pooled analysis of infections, malignancy, and mortality in infliximab- and immunomodulator-treated adult patients with inflammatory bowel disease.
abstract: OBJECTIVE
  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 10 mg/kg (n=1,713; ±azathioprine) or placebo (n=406; ±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.
authors.affiliation: Division of Gastroenterology, Hospital of The University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. grl@uphs.upenn.edu
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lichtenstein
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Sands
authors.forename: Robert H
authors.initials: RH
authors.lastname: Diamond
authors.forename: Marion
authors.initials: M
authors.lastname: Blank
authors.forename: Jennifer
authors.initials: J
authors.lastname: Montello
authors.forename: Linda
authors.initials: L
authors.lastname: Tang
authors.forename: Freddy
authors.initials: F
authors.lastname: Cornillie
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000401:mortality*; D016001:Confidence Intervals; D003424:Crohn Disease / Q000188:drug therapy* / Q000401:mortality*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D007239:Infections / Q000453:epidemiology*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology*; D017063:Outcome Assessment, Health Care; D016032:Randomized Controlled Trials as Topic; D018426:SEER Program; D014481:United States / Q000453:epidemiology
chemical_list: D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069285:Infliximab