The treatment efficacy of adding prokinetics to PPIs for gastroesophageal reflux disease: a meta-analysis

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder. Proton pump inhibitors (PPIs) are first-line drugs for GERD. For those who fail to respond to PPIs, adding prokinetics to PPIs is recommended and several trials have been conducted to evaluate the efficacy of prokinetic–PPI combination therapy. A systematic literature search was performed using PubMed and the Cochrane Library databases before February 2019 for randomized controlled trials (RCTs), which compared the efficacy of prokinetics plus PPI treatment with that of PPI monotherapy. Relevant studies were examined and data were extracted independently by two investigators. The risk ratios (RRs) with 95% CIs were used to evaluate the responder rate, and standard mean differences (SMDs) or mean differences (MDs) with 95% CIs were used for symptom score changes. Statistical heterogeneity was evaluated by the I2 statistic. Either a fixed-effect or a random-effect model was established for calculating the pooled data. A total of 14 studies, comprising 1,437 patients were ultimately included in the meta-analysis. The pooled analysis showed that compared to PPI monotherapy, addition of prokinetics to PPI did not elevate the rate of endoscopic responders (RR = 0.996, 95% CI 0.929 − 1.068, p = 0.917), but improved symptom response (RR = 1.185, 95% CI 1.042 − 1.348, p = 0.010). Additionally, the combined therapy achieved a greater symptom relief than monotherapy both in FSSG and GERD-Q subgroups (MD = − 2.978, 95% CI − 3.319 to − 2.638, p