title: Anti tumour necrosis factor as risk factor for free perforations in Crohn's disease? A case-control study.
abstract: OBJECTIVE
  Although the occurrence of intestinal perforation in Crohn's disease (CD) is rare, clinical observation has led to the question whether anti tumour necrosis factor (TNF) treatment is a risk factor for free perforation. The aim of this study was to investigate the possible relation between anti-TNF treatment and occurrence of free perforation, defined as intestinal perforations leading to emergency surgery.
  
  
  METHODS
  In this case-control study, all emergency operation reports from the period 1999-2009 of patients diagnosed with CD were checked for the presence of free perforation. These cases were compared with a sixfold larger control group derived from our CD patient database. Cases and controls were matched for age, gender, Montreal classification and surgical stage to ensure equal disease severity. Cases and controls were then compared regarding previous or current exposure to anti-TNF treatment.
  
  
  RESULTS
  Thirteen patients underwent emergency surgery for spontaneous free perforation. Eight (62%) had been treated with anti-TNF within 5 months before the perforation. In the 78 matched controls, 29 (37%) had been or were still treated with anti-TNF. The odds for a free perforation adjusted for known confounders in two separate regression analyses were significantly higher in anti-TNF treated CD patients, albeit with a large confidence interval (OR 4.1, 95% CI: 1.1-16.0; and OR 23.0, 95% CI 2.2-238.5).
  
  
  CONCLUSIONS
  This study showed a higher occurrence of free perforations in CD patients with anti-TNF therapy compared with those without anti-TNF therapy. Patients with CD and anti-TNF treatment showing acute abdominal pain must be suspected of this complication.
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, Amsterdam, The Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: Eshuis
authors.forename: G H M J
authors.initials: GH
authors.lastname: Griffioen
authors.forename: P C F
authors.initials: PC
authors.lastname: Stokkers
authors.forename: D T
authors.initials: DT
authors.lastname: Ubbink
authors.forename: W A
authors.initials: WA
authors.lastname: Bemelman
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D016001:Confidence Intervals; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000069285:Infliximab; D007416:Intestinal Perforation / Q000139:chemically induced* / Q000601:surgery; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018570:Risk Assessment; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab