We assessed the risk-benefit profile of anti-4-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)- exposure and estimated summary relative risk (RR) or mean difference, with 95% confidence intervals (CIs).Results:Anti-4-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-4-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.