title: Ischaemic colitis in rheumatoid arthritis patients receiving tumour necrosis factor-α inhibitors: an analysis of reports to the US FDA Adverse Event Reporting System.
abstract: BACKGROUND
  Tumour necrosis factor-α (TNF-α) inhibitors are immunosuppressants, approved for the treatment and maintenance of rheumatoid arthritis (RA). Immunosuppression has been shown to induce ischaemic colitis (IC) in an animal model; however, a relationship between TNF inhibitors and IC has rarely been reported in the published literature.
  
  
  OBJECTIVE
  The aim of this study was to better characterize the association between TNF-α inhibitors with IC in RA patients, by analysing adverse event reports submitted to the US FDA Adverse Event Reporting System (AERS) and the published literature.
  
  
  METHODS
  The FDA AERS database was searched and we identified all reports between January 2003 and June 2011. The search was limited to an indication of RA, a 'primary suspect' drug of TNF-α inhibitors and a reaction of IC. Full-length reports were obtained and analysed utilizing the Freedom of Information Act. The cases were organized by age, sex, type of TNF-α inhibitor, concomitant drugs and medical co-morbidities. Cases were labelled as definite, probable, possible or doubtful drug-induced adverse events based on the Naranjo Scale. A PubMed search was performed to obtain published literature documenting events of anti-TNF-associated IC.
  
  
  RESULTS
  Twelve cases were eliminated because of more likely causes for IC. Thirty-five primary suspect reports of TNF-α inhibitors associated with IC in RA patients were identified in the FDA AERS. Thirteen cases were reported with infliximab, 12 with adalimumab, 7 with etanercept and 3 with certolizumab. The majority of the cases were in females (29/35) and those between the ages of 50 and 65 years (18/35). Use of the Naranjo Scale revealed 17 probable and 18 possible cases of anti-TNF-induced IC. In the literature, one report of IC associated with adalimumab was identified.
  
  
  CONCLUSIONS
  TNF-α inhibitors may be initiating factors or co-factors in the development of IC in RA patients, and further research to determine the mechanism of this association is warranted.
authors.affiliation: Center for the Study of Complex Diseases, Research Institute, North Shore University Health System, 1001 University Place, Evanston, IL 60201, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Salk
authors.forename: Derrick J
authors.initials: DJ
authors.lastname: Stobaugh
authors.forename: Parakkal
authors.initials: P
authors.lastname: Deepak
authors.forename: Eli D
authors.initials: ED
authors.lastname: Ehrenpreis
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology; D017091:Colitis, Ischemic / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058028:Research Report; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014481:United States; D014486:United States Food and Drug Administration / Q000706:statistics & numerical data
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha