Systematic Review of Therapeutic Interventions for PPI Non-responsive Gastroesophageal Reflux Disease

Abstract

Introduction: While laparoscopic fundoplication (LF) has been the treatment of choice for patients with gastroesophageal reflux disease (GERD) who remain symptomatic despite proton pump inhibitor (PPI) therapy, emerging interventions offer an alternative option. The aim of this study was to perform a systematic literature review to report symptomatic and physiologic impacts of therapeutic interventions to treat PPI nonresponsive GERD. Methods: A review of the PubMed, Cochrane, and EMBASE databases from 2005-2015 for GERD therapeutic interventions identified 2928 unique citations. All full-text, English language studies reporting interventions in adult populations with typical GERD symptoms on at least once daily PPI were included. Fifty-one studies met inclusion criteria and were categorized according therapy type: LF (21), endoscopic fundoplication (EF) (11), radiofrequency delivery (RFD) (10), magnetic sphincter augmentation (MSA) (6) and other (3) [Figure 1].Figure 1Results: As far out as 10 years, LF improves symptoms and physiologic parameters as measured by pH testing according; but PPI use increases (8.8% to 18.2%). EF improves GERD symptoms and eliminates PPI use in 58-93% of cases, but longest follow-up time is 3 years. In the only comparison of EF and LF, an open-label trial found better symptom remission rates (100% vs. 30%) and normalization of esophageal acid exposure (100% vs. 50%) with LF. RFD has mixed results. PPI independence ranges from 6.25-86.3% with RFD and only modest reductions in esophageal acid exposure (11.6% to 8.5%). MSA improves symptoms as far out as 5 years with normalization of acid exposure in 80% of patients and elimination of PPI in 75.3%. In an observational study, MSA, as compared to LF, provides similar improvements in GERD-HQRL scores, greater reduction in PPI use and better preservation of the ability to belch and vomit. Electrical stimulation of the lower esophageal sphincter, submucosal dissection and mucosal resection are emerging techniques that warrant further study. Results summarized in Figure 2.Figure 2Conclusion: LF remains the most proven option for the treatment of PPI nonresponsive GERD. EF and MSA are promising techniques with potentially fewer side effects, while evidence forRFD is mixed. Longer term, randomized trials comparing new techniques with LF are needed.