title: Systematic review and meta-analysis: opportunistic infections and malignancies during treatment with anti-integrin antibodies in inflammatory bowel disease.
abstract: BACKGROUND
  Anti-integrin antibodies are effective therapies for Crohn's disease (CD) and ulcerative colitis (UC). However, these drugs carry theoretical risks of opportunistic infection and malignancy.
  
  
  OBJECTIVE
  To pool data from all placebo-controlled studies, to estimate risk of opportunistic infection or malignancy with anti-integrin antibodies.
  
  
  METHODS
  MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched (up to December 2014). Randomised placebo-controlled trials of anti-integrin antibodies in adults with active or quiescent CD or UC were eligible. Dichotomous data were pooled to obtain a relative risk (RR) of opportunistic infection or malignancy, with 95% confidence intervals (CIs).
  
  
  RESULTS
  The search strategy identified 1579 citations, 12 of which were eligible (four trials of natalizumab, six of vedolizumab and two of etrolizumab). The RR of developing an opportunistic infection was not significantly higher with non-gut specific (2.34; 95% CI 0.05-108.72) or gut specific anti-integrin antibodies (1.55; 95% CI 0.16-14.83). The RR was generally higher in trials of non-gut specific anti-integrin antibodies with duration of therapy ≥52 weeks (RR = 15.00; 95% CI 0.86-261), but remained non-significant. The RR of malignancy was not elevated with non-gut specific (1.57; 95% CI 0.19-12.74) or gut specific anti-integrin antibodies (0.78; 95% CI 0.15-4.02).
  
  
  CONCLUSIONS
  Absolute numbers of opportunistic infections were higher with anti-integrin antibodies, but this difference is not statistically significant. There was no increased risk of malignancy detected. Long-term data in large prospective cohorts are needed to further assess this issue.
authors.affiliation: Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.
authors.forename: P
authors.initials: P
authors.lastname: Luthra
authors.affiliation: Inserm U954 and Department of Hepatogastroenterology, Nancy University Hospital, Lorraine University, Vandoeuvre-les-Nancy, France.
authors.forename: L
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.affiliation: Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.|Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Ford
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003093:Colitis, Ulcerative / Q000188:drug therapy; D003424:Crohn Disease / Q000188:drug therapy; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D016023:Integrins / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D000069442:Natalizumab; D009369:Neoplasms / Q000139:chemically induced*; D009894:Opportunistic Infections / Q000139:chemically induced*; D011446:Prospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016023:Integrins; D000069442:Natalizumab; C543529:vedolizumab