Supplementary Material for: Does manual acupuncture improve gastro-esophageal reflux disease symptoms? A trial sequential meta-analysis

Introduction: The role of acupuncture in treating gastro-esophageal reflux disease (GERD) has been previously investigated; however, it’s unclear whether manual acupuncture is effective for treating GERD. This study aimed to evaluate the effectiveness and safety of manual acupuncture in treating GERD.
Methods: Potentially eligible studies were identified from PubMed, Embase, Cochrane Central Registry for Controlled Trials(CENTRAL), China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature database (Sinomed). Sensitivity analysis was conducted through excluding low-quality studies. Subgroup analysis was performed according to different proton pump inhibitors (PPIs) and treatment duration. Certainty of evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework.
Results: Based on 504 records, 12 relevant studies was included in our meta-anaysis. Trial sequential analysis confirmed that manual acupuncture improved symptom scores (mean difference [MD]=-3.43, 95% CI=-5.14 to -1.73, I2=88%, P<0.001, very low evidence) and reduced recurrence rates (risk ratio [RR]=0.32, 95% confidence interval=0.16 to 0.64, I2=0%, P=0.001, very low evidence). Although meta-analysis showed no difference in adverse events between manual acupuncture and PPIs (RR=0.38, 95% CI=0.09 to 1.58, I2=0%, P=0.18, very low evidence), TSA revealed extremely insufficient statistical power. Furthermore, the global symptom improvement rate was lower with acupuncture compared to PPIs (RR=1.22, 95%CI=1.14 to 1.30, I2=18%, P<0.001, low evidence). Sensitivity analysis demonstrated the robustness of results. Subgroup analysis suggested the therapeutic effects of manual acupuncture alone irrespective of categories of PPIs and treatment duration.
Conclusion: Manual acupuncture has the potential to alleviate the severity of symptoms and decrease the recurrence rate in patients with GERD. However, considering the efficacy of PPI therapy in significantly improving overall symptoms, along with its established safety profile and extensive clinical utilization over the years, we do not recommend manual acupuncture alone as the primary treatment for patients with GERD.