S482 Evaluating Multiple Dosing Regimens for Proton Pump Inhibitors (PPI) for the Treatment of Gastroesophageal Reflux Disease (GERD): A Systematic Review and Meta-Analysis

Abstract

Introduction: Although once-daily dosing of PPI therapy for GERD is standard of practice, clinicians often use twice daily dosing. It remains unclear if this common practice meaningfully improves GERD symptoms of heartburn and/or regurgitation. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing for resolution of GERD, heartburn, and esophageal healing with regards to various PPI dosages and frequencies. Methods: A search of EMBASE and PubMed in October 2021 yielded 1381 unique records. Abstract/title screening and full-text review were completed by two independent reviewers, where 51 studies were included in the systematic review and 37 RCTs were included in the quantitative analysis; all included studies compared different doses within PPI. Data abstraction was performed in duplicate using Systematic Review Data Repository+, with discrepancies resolved by a third reviewer. The outcomes were resolution of GERD, heartburn, and esophageal healing within 12 weeks. Risk of bias was independently assessed using the Cochrane Risk of Bias tool (v2). Random-effects meta-analyses were conducted in Stata. Studies were excluded from quantitative review if they did not report outcomes of interest, only assessed outcomes after 12 weeks, or compared out-of-practice dosages (quarter and quadruple standard dose). Results: A total of 51 RCTs conducted across 27 countries (n=20,226 patients, 55% male, mean age 50 years) were included in the systematic review. Among 37 RCTs included in the quantitative analysis, most compared double standard dose daily vs. standard dose daily or standard dose daily vs. half standard dose daily; few studies compared daily vs. twice daily dosing. Table shows odds ratios (OR) and 95% confidence intervals (CI) for outcomes among the various dosing comparisons. For example, when compared to standard dose daily, double standard dose daily led to improved outcomes for GERD (OR 1.35, 95% CI 1.01-1.75) and esophageal healing (OR 1.62, 95% CI 1.27-2.07), but not for heartburn (OR 1.08, 95% CI 0.94-1.24) (Figure). Conclusion: Our meta-analysis revealed, in general, that increasing PPI daily dosages was associated with improved outcomes. However, few studies compared daily vs. twice daily PPI. As twice daily PPI usage is common in clinical practice, further studies are needed to determine whether twice daily dosing actually improves clinical outcomes.Figure 1.: Forest plot comparison for Standard dose, QD vs. Double Standard dose, QD in resolution of GERD symptoms (1A) and Heartburn (1B). Table 1 - Dosing Comparisons across Randomized Controlled Trials (≤12 weeks) Dosing Comparison Total Number of RCTs Total Number of Patients Outcome OR (95% Cl) Standard dose BID vs.Standard dose QD (ref) 1 202 Esophageal healing 2.34 (1.27, 4.31) * 1 202 Heartburn 3.03 (1.62, 5.68) * Double standard dose QD vs.Standard dose QD (ref) 7 2408 Esophageal healing 1.62 (1.27, 2.07) * 6 1312 GERD 1.35 (1.05, 1.75) * 5 3433 Heartburn 1.08 (0.94, 1.24) Double standard dose, BID vs.Standard dose QD (ref) 1 197 Heartburn 0.77 (0.44, 1.35) Standard dose QD vs.Half standard dose QD (ref) 9 1762 Esophageal healing 1.79 (1.44, 2.22) * 8 1718 GERD 1.42 (1.15, 1.76) * 14 3327 Heartburn 1.41 (1.17, 1.69) * Standard dose QD vs.Half standard dose BID (ref) 2 411 Esophageal healing 1.94 (1.15, 3.26) * 1 205 Heartburn 2.14 (1.19, 3.85) * Double standard dose BID vs.Double standard dose QD (ref) 1 190 Heartburn 0.90 (0.51, 1.60) 1 200 GERD 2.63 (1.30, 5.35) * Standard dose BID vs.Half standard dose BID (ref) 1 202 Esophageal Healing 0.92 (0.47, 1.79) 1 203 Heartburn 1.42 (0.74, 2.74) Half Standard dose, BID vs.Half standard dose QD (ref) 1 324 Esophageal Healing 7.43 (3.81, 14.49) * *p< 0.05.QD=daily, BID=twice daily