Effectiveness and Tolerability of Different Recommended Doses of PPIs and H2RAs in GERD: Network Meta-Analysis and GRADE system

Abstract

Proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) are used for gastro-esophageal reflux disease (GERD); however, the clinical evidence for treatment is poor. We evaluated the effectiveness and tolerability of different doses of PPIs, H2RAs and placebo in adults with GERD. Six online databases were searched through September 1, 2016. All related articles were included and combined with a Bayesian network meta-analysis from randomized controlled trials (RCTs). The GRADE systems were employed to assess the main outcome. Ninety-eight RCTs were identified, which included 45,964 participants. Our analysis indicated that the full/standard dose of esomeprazole at 40 mg per day was the most efficient in healing among nine different dosages of PPIs and H2RAs. The main efficacy outcome did not change after adjustments for the area, age, level of disease from endoscopy, year of publication, pharmaceutical industry sponsorship, Intention-to-treat (ITT)/per-protocol (PP), withdrawal rate, pre-set select design bias, single blinded and unblinded studies, study origination in China, study arms that included zero events, inconsistency node or discontinued drug were accounted for in the meta-regressions and sensitivity analyses. This research suggests that the full/standard doses (40 mg per day) of esomeprazole should be recommended as first-line treatments for GERD in adults for short-term therapy.

Vonoprazan versus proton‐pump inhibitors for healing gastroesophageal reflux disease: A systematic review

“…Zhang et al . reported that PPIs are more effective than H 2 RAs and that esomeprazole (40 mg) was the most effective treatment in the study . In our study, the OR to placebo was also highest for esomeprazole (40 mg) among the PPIs with the same dosage as in the Zhang et al .…”

“…Network meta‐analyses of RCTs, comparing PPI efficacy in healing GERD, were previously conducted by Zhang et al . and Li et al .…”

“…Our analysis may therefore provide useful information for clinicians, enabling them to offer better choices of treatment to patients with GERD. Network meta-analyses of RCTs, comparing PPI efficacy in healing GERD, were previously conducted by Zhang et al 71 and Li et al 72 Zhang et al reported that PPIs are more effective than H 2 RAs and that esomeprazole (40 mg) was the most effective treatment in the study. 71 In our study, the OR to placebo was also highest for esomeprazole (40 mg) 72 Our results generally support these findings regarding 40 mg esomeprazole, despite the differences between the analyses.…”

“…In addition, we searched only MEDLINE and CENTRAL and did not use EMBASE due to lack of access. In a comparison of GERD healing efficacy in PPIs and H 2 RAs, Zhang et al included 50 studies from MEDLINE, CENTRAL, EMBASE, and ClinicalTrials.gov, 71 which are more than the 41 studies in this analysis. The difference is probably due to the difference in searched data sources.…”

Systematic review with network meta-analysis: indirect comparison of the efficacy of vonoprazan and proton-pump inhibitors for maintenance treatment of gastroesophageal reflux disease

“…Previously, Li et al [45] and Zhang et al [46] reported the comparative efficacy of different PPIs in healing GERD and relieving its symptoms, as well as the acceptability/tolerability of PPIs by network meta-analysis. However, to our knowledge, the comparative efficacy of different PPIs for the maintenance treatment of GERD and that of PPIs and vonoprazan have not been conducted to date.…”