In the present study, we aimed to systematically evaluate the efficacy of the combination therapy of prokinetics and proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD), and to provide an evidence-based reference for clinical use. The pertinent randomized controlled trials (RCTs) were retrieved from PubMed and Embase. The quality of included studies was evaluated using the "risk of bias" tool for RCTs using the RevMan 5.3. Related data were extracted according to the preset data collection forms. Meta-analysis was performed using RevMan 5.3 and Stata 12.0 statistical software. Mean difference (MD) was used to describe the continuous variables, and relative ratio (RR) was used for classification variables. A total of 13 RCTs involving 1388 patients were included. Results of the meta-analysis showed that compared with PPI monotherapy, the combination therapy significantly improved the total response rate (RR = 1.15, 95% confidence interval (CI): (1.07, –1.24), P < 0.001), gastroesophageal reflux disease questionnaire (GERD-Q) score (MD = –1.38, 95% CI: (–2.12, –0.64), P < 0.001), the frequency scale for the symptoms of gastroesophageal reflux (FSSG) score (MD = 2.11, 95% CI: (1.68, 2.54), P < 0.001) and visual analogue scale (MD = –0.69, 95% CI: (–0.93, –0.45), P < 0.001). However, the endoscopic response (RR = 1.08, 95% CI: (0.99, 1.18), P = 0.10) and symptomatic response (RR = 1.22, 95% CI: (0.94, 1.59), P = 0.13) were not significantly different between the two groups. For patients with GERD, the combination therapy could markedly improve the total response rate (symptomatic response and/or endoscopic response) and quality of life, while no benefits were found in symptomatic and endoscopic response. In view of the small number of participants included and some confounding factors in this study, the conclusion made in this study needs to be further confirmed by including a large number of participants and performing high-quality RCTs.
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