title: Serious adverse events with infliximab: analysis of spontaneously reported adverse events.
abstract: OBJECTIVE
  Serious adverse events such as bowel obstruction, heart failure, infection, lymphoma, and neuropathy have been reported with infliximab. The aims of this study were to explore adverse event signals with infliximab by using a long period of post-marketing experience, stratifying by indication.
  
  
  METHODS
  The relative reporting of infliximab adverse events to the U.S. Food and Drug Administration (FDA) was assessed with the public release version of the adverse event reporting system (AERS) database from 1968 to third quarter 2005. On the basis of a systematic review of adverse events, Medical Dictionary for Regulatory Activities (MedDRA) terms were mapped to predefined categories of adverse events, including death, heart failure, hepatitis, infection, infusion reaction, lymphoma, myelosuppression, neuropathy, and obstruction. Disproportionality analysis was used to calculate the empiric Bayes geometric mean (EBGM) and corresponding 90% confidence intervals (EB05, EB95) for adverse event categories.
  
  
  RESULTS
  Infliximab was identified as the suspect medication in 18,220 reports in the FDA AERS database. We identified a signal for lymphoma (EB05 = 6.9), neuropathy (EB05 = 3.8), infection (EB05 = 2.9), and bowel obstruction (EB05 = 2.8). The signal for granulomatous infections was stronger than the signal for non-granulomatous infections (EB05 = 12.6 and 2.4, respectively). The signals for bowel obstruction and infusion reaction were specific to patients with IBD; this suggests potential confounding by indication, especially for bowel obstruction.
  
  
  CONCLUSIONS
  In light of this additional evidence of risk of lymphoma, neuropathy, and granulomatous infections, clinicians should stress this risk in the shared decision-making process.
authors.affiliation: Center for Pharmaceutical Outcomes and Policy, Division of Pharmaceutical Outcomes and Policy, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. rahansen@unc.edu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hansen
authors.forename: Gerald
authors.initials: G
authors.lastname: Gartlehner
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Powell
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001499:Bayes Theorem; D015340:Epidemiologic Research Design; D006099:Granuloma / Q000139:chemically induced; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D000069285:Infliximab; D008223:Lymphoma / Q000139:chemically induced; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab