A systematic review and meta-analysis of randomized control trials: Combination treatment with proton pump inhibitor plus prokinetic for gastroesophageal reflux disease

Background/Aims Prokinetics can be used for treating patients with gastroesophageal reflux disease (GERD), who exhibit suboptimal response to proton pump inhibitor (PPI) treatment. We conducted a systematic review to assess the potential benefits of combination treatment with PPI plus prokinetics in GERD. Methods We searched PubMed, the Cochrane Library, and EMBASE for publications regarding randomized controlled trials comparing combination treatment of PPI plus prokinetics to PPI monotherapy with respect to global symptom improvement in GERD (until February 2020). The primary outcome was an absence or global symptom improvement in GERD. Adverse events and quality of life (QoL) scores were evaluated as secondary outcomes using a random effects model. Quality of evidence was rated using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results This meta-analysis included 16 studies involving 1446 participants (719 in the PPI plus prokinetics group and 727 in the PPI monotherapy group). The PPI plus prokinetics treatment resulted in a significant reduction in global symptoms of GERD regardless of the prokinetic type, refractoriness, and ethnicity. Additionally, treatment with PPI plus prokinetics for at least 4 weeks was found to be more beneficial than PPI monotherapy with respect to global symptom improvement. However, the QoL scores were not improved with PPI plus prokinetics treatment. Adverse events observed in response to PPI plus prokinetics treatment did not differ from those observed with PPI monotherapy. Conclusions Combination of prokinetics with PPI treatment is more effective than PPI alone in GERD patients. Further high-quality trials with large sample sizes are needed to verify the effects based on prokinetic type.