S930 Assess Comparative Efficacy, Quality-of-Life Impact, Safety Profile, and Onset of Action of Proton Pump Inhibitors (PPIs) vs Antacids in Adults With Rome IV-Defined Non-Erosive Reflux Disease (NERD): A Meta-Analysis

Introduction: To assess the comparative efficacy, quality-of-life impact, safety profile, and onset of action of proton pump inhibitors (PPIs) versus antacids in adults with Rome IV-defined non-erosive reflux disease (NERD), using only low-heterogeneity, low-bias randomized controlled trials (RCTs). Methods: A systematic review and meta-analysis was conducted using PubMed, Embase, and Cochrane databases (2015-2023). Eligible studies directly compared esomeprazole or pantoprazole to magnesium-/aluminum-based antacids in adult NERD populations meeting Rome IV criteria. Primary outcomes included symptom relief (risk ratio [RR]) and gastroesophageal reflux disease (GERD)-specific quality of life (GERD-HRQL). Secondary outcomes included adverse events (risk difference [RD]) and onset of symptom relief (hazard ratio [HR]). Risk of bias was assessed using Cochrane Risk of Bias 2.0. Results: Of the 1,624 record screened, 8 RCTs (N = 4,850) were included. All had low risk of bias and heterogeneity (I² < 25%). PPIs significantly improved 8-week symptom relief over antacids (RR 1.42; 95% CI 1.31-1.54; I² = 11%). Quality of life also favored PPIs (mean difference 2.27; 95% CI 2.23-3.31; I² = 0%). PPIs were associated with increased risk of hypomagnesemia (RD 0.09; 95% CI 0.05-0.12), while antacids had a slightly higher incidence of diarrhea (RD -0.08; 95% CI -0.16 to -0.01). Antacids acted significantly faster (HR 0.14; 95% CI 0.07-0.28). Conclusion: PPIs remain superior for long-term symptom control and quality of life in NERD, though antacids provide faster onset and are better tolerated in some populations. A sequential approach—initiating PPIs for sustained control with antacid rescue—may balance efficacy and tolerability. Recent impedance-pH studies further classify NERD into acid-sensitive, weakly acidic, and functional heartburn subtypes, with PPIs effective primarily in acid-sensitive subgroups. This underscores the need for phenotype-specific therapy, which our analysis addresses by isolating Rome IV-defined populations. This meta-analysis provides robust, clinically relevant evidence that PPIs offer superior long-term symptom relief and quality-of-life improvement in adults with Rome IV-defined non-erosive reflux disease (NERD). However, magnesium/aluminum-based antacids demonstrate a significantly faster onset of action and may be better tolerated in specific subgroups, such as patients with overlapping functional bowel disorders.