title: Efficacy and Safety of Natalizumab and Vedolizumab for the Management of Crohn's Disease: A Systematic Review and Meta-analysis.
abstract: BACKGROUND
  We assessed the risk-benefit profile of anti-α4-integrins, natalizumab (NAT), and vedolizumab (VEDO), in Crohn's disease through a systematic review and meta-analysis of randomized controlled trials.
  
  
  METHODS
  We searched multiple electronic databases through July 2014 and identified 8 randomized controlled trials in adults with Crohn's disease comparing NAT (5 trials) or VEDO (3 trials) with placebo. Efficacy outcomes were induction of remission, response, and improvement in quality of life; safety outcomes were serious adverse events, infusion reactions, infections, and treatment discontinuation. We performed subgroup analysis based on anti-tumor necrosis factor (TNF)-α exposure and estimated summary relative risk (RR) or mean difference, with 95% confidence intervals (CIs).
  
  
  RESULTS
  Anti-α4-integrins were superior to placebo for induction of remission (RR, 0.87; 95% CI, 0.84-0.91), with similar estimates for NAT (RR, 0.86; 95% CI, 0.80-0.93) and VEDO (RR, 0.87; 95% CI, 0.79-0.95). Both NAT and VEDO were equally efficacious for anti-TNF-naive (NAT: RR, 0.87; 95% CI, 0.75-1.00; VEDO: RR, 0.86; 95% CI, 0.79-0.94) and anti-TNF-exposed patients (NAT: RR, 0.86; 95% CI, 0.76-0.99; VEDO: RR, 0.89; 95% CI, 0.78-1.01). Anti-α4-integrins were effective in inducing clinical response and improving quality of life, with no significant difference between NAT and VEDO. Rates of serious adverse events, infusion reactions, infections, and treatment discontinuation were similar for NAT and VEDO. No cases of progressive multifocal leukoencephalopathy have been observed with VEDO to date.
  
  
  CONCLUSIONS
  NAT and VEDO are effective in inducing remission and response in patients with Crohn's disease, with similar efficacy in anti-TNF-naive and anti-TNF-exposed patients.
authors: *Division of Gastroenterology and Liver Diseases, Case Western Reserve University, Cleveland, Ohio; †Digestive Health Institute, University Hospitals Case Medical Center, Cleveland, Ohio; ‡Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota; §Knowledge and Evaluation Research Unit, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota; and ‖Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy-Brabois, Université de Lorraine, Vandoeuvre-lès-Nancy, France.
authors: Apoorva K
authors: AK
authors: Chandar
authors: Siddharth
authors: S
authors: Singh
authors: Mohammad Hassan
authors: MH
authors: Murad
authors: Laurent
authors: L
authors: Peyrin-Biroulet
authors: Edward V
authors: EV
authors: Loftus
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy*; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D000069442:Natalizumab / Q000627:therapeutic use*; D012074:Remission Induction
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005765:Gastrointestinal Agents; D007155:Immunologic Factors; D000069442:Natalizumab; C543529:vedolizumab