Rebamipide Helps Defend Against Nonsteroidal Anti-Inflammatory Drugs Induced Gastroenteropathy: A Systematic Review and Meta-Analysis

Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) has been perplexing most clinicians and users of NSAIDs. Rebamipide is increasingly advocated as a candidate option for the prevention of NSAIDs induced gastrointestinal mucosal injury. To assess the efficacy and the safety of rebamipide for the prevention and treatment of NSAID-induced gastroenteropathy. PubMed, Embase, Web of Science, Google Scholar, the Cochrane Library, Japan Science and Technology Information Aggregator, and China Biology Medicine Disc were searched up to December 2011. Randomized controlled trials (RCTs) recruiting subjects with co-prescriptions of NSAIDs and rebamipide were eligible. Efficacy and safety of rebamipide were reevaluated, and dichotomous data were pooled to obtain relative risk (RR) with a 95 % confidence interval. Heterogeneity and publication bias were assessed by the inconsistency index statistic and funnel plot analysis, respectively. The search identified 338 citations, and 15 RCTs including 965 individuals were eligible. In general, rebamipide acted better than placebo against short-term NSAID-induced gastroduodenal injury. Separate studies showed rebamipide was equal to or not superior to traditional strategies (including PPIs, H2RA and misoprostol treatment). Especially, rebamipide showed a beneficial effect against the small bowel damage (total RR = 2.70, 95 % confidence interval = 1.02-7.16, P = 0.045) when compared with placebo group. The average incidence of adverse events was about 36.1 % (0-70.0 %) but no serious event was recorded. Current evidences show rebamipide is effective and safe for defending against NSAID-induced gastroduodenal and lower-gastrointestinal injuries. However, more well-designed trials should be conducted to fully confirm the practical value of rebamipide.