Reassessing Vonoprazan for Endoscopy-Negative Reflux Disease: A Systematic Review and Meta-Analysis

Non-erosive reflux disease (NERD) is characterized by reflux without esophageal erosions. Vonoprazan, a potassium-competitive acid blocker, is recommended for patients with erosive esophagitis (EE). However, its role in NERD, remains limited. We conducted a systematic review and meta-analysis to assess its efficacy in patients with NERD.

A systematic literature search was conducted, on MEDLINE, Embase and Cochrane Library until January 25, 2025, to identify all randomized controlled trials (RCTs) comparing Vonoprazan to placebo in patients with NERD. Binary and continuous outcomes were pooled using risk ratios (RRs), and standardized mean differences (SMDs), respectively, along with their 95% confidence intervals (CIs).

Four RCTs with a total of 2540 patients (50.3% females) were included. Vonoprazan 10 mg was comparable to placebo in terms of mean proportion of days without heartburn (SMD: 0.12; 95% CI - 0.04-0.29, p = 0.14), mean severity score of heartburn (SMD: 0.01; 95% CI - 0.15-0.17, p = 0.94), treatment-related adverse events (RR: 0.93; 95% CI: 0.71-1.20, p = 0.568), and serious adverse events (RR: 1.46; 95% CI 0.23-9.23, p = 0.689). Vonoprazan 20 mg was superior to placebo in terms of mean proportion of days without heartburn (SMD: 0.13; 95% CI 0.01-0.24 p = 0.03), with comparable results for mean severity score of heartburn (SMD: - 0.03; 95% CI - 0.15-0.08 p = 0.56), treatment-related adverse events (RR: 1.11; 95% CI 0.52-2.36 p = 0.785), and serious adverse events (RR: 6.03; 95% CI 0.73-50.10 p = 0.096).

Vonoprazan 10 mg showed no benefit over placebo in NERD. The 20 mg dose modestly increased heartburn-free days with similar safety, suggesting potential efficacy.