{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:14:19Z","timestamp":1792084459954,"version":"4.4.0"},"reference-count":70,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T00:00:00Z","timestamp":1664064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The comparative efficacy and safety of medical therapies for gastro\u2010esophageal reflux symptoms in endoscopy\u2010negative reflux disease is unclear. We conducted a network meta\u2010analysis to evaluate efficacy and safety of proton pump inhibitors (PPIs), histamine\u20102\u2010receptor antagonists, potassium\u2010competitive acid blockers (PCABs), and alginates in patients with endoscopy\u2010negative reflux disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to February 1, 2022. We included randomized controlled trials (RCTs) comparing efficacy of all drugs versus each other, or versus a placebo, in adults with endoscopy\u2010negative reflux disease. Results were reported as pooled relative risks with 95% confidence intervals to summarize effect of each comparison tested, with treatments ranked according to <jats:italic>P<\/jats:italic>\u2010score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>We identified 23 RCTs containing 10,735 subjects with endoscopy\u2010negative reflux disease. Based on failure to achieve complete relief of symptoms between \u22652 and\u2009&lt;4\u2009weeks, omeprazole 20\u2009mg o.d. (<jats:italic>P<\/jats:italic>\u2010score 0.94) ranked first, with esomeprazole 20\u2009mg o.d. or 40\u2009mg o.d. ranked second and third. In achieving adequate relief, only rabeprazole 10\u00a0mg o.d. was significantly more efficacious than placebo. For failure to achieve complete relief at \u22654\u2009weeks, dexlansoprazole 30\u2009mg o.d. (<jats:italic>P<\/jats:italic>\u2010score 0.95) ranked first, with 30\u2009ml alginate q.i.d. combined with omeprazole 20\u2009mg o.d., and 30\u2009ml alginate t.i.d. second and third. In terms of failure to achieve adequate relief at \u22654\u2009weeks, dexlansoprazole 60\u2009mg o.d. ranked first (<jats:italic>P<\/jats:italic>\u2010score 0.90), with dexlansoprazole 30\u2009mg o.d. and rabeprazole 20\u2009mg o.d. second and third. All drugs were safe and well\u2010tolerated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Our results confirm superiority of PPIs compared with most other drugs in treating endoscopy\u2010negative reflux disease. Future RCTs should aim to better classify patients with endoscopy\u2010negative reflux disease, and to establish the role of alginates and PCABs in achieving symptom relief in both the short\u2010 and long\u2010term.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14469","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T16:55:32Z","timestamp":1664124932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Comparison of acid\u2010lowering drugs for endoscopy negative reflux disease: Systematic review and network <scp>Meta\u2010Analysis<\/scp>"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3164-8243","authenticated-orcid":false,"given":"Brigida","family":"Barberio","sequence":"first","affiliation":[{"name":"Division of Gastroenterology Department of Surgery, Oncology and Gastroenterology University of Padua  Padua 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Technologies in Medicine and Surgery University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5449-3603","authenticated-orcid":false,"given":"Christopher J.","family":"Black","sequence":"additional","affiliation":[{"name":"Leeds Gastroenterology Institute St. James's University Hospital  Leeds UK"},{"name":"Leeds Institute of Medical Research at St. James's University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6371-4359","authenticated-orcid":false,"given":"Alexander C.","family":"Ford","sequence":"additional","affiliation":[{"name":"Leeds Gastroenterology Institute St. James's University Hospital  Leeds UK"},{"name":"Leeds Institute of Medical Research at St. James's University of Leeds  Leeds 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