Efficacy and Safety of Vonoprazan in Dual/Triple/Quadruple Regimens Both in First‐Line and Rescue Therapy for Helicobacter pylori Eradication: A Systematic Review With Meta‐Analysis

BACKGROUND: The efficacy of Helicobacter pylori (H. pylori) eradication therapies encompassing one or more antibiotics and a proton pump inhibitor (PPI) has lately decreased. Vonoprazan (VPZ), a potassium-competitive acid blocker, provides higher gastric acid suppression than PPIs. We performed a meta-analysis evaluating the efficacy and safety of VPZ in H. pylori eradication therapies. METHODS: Studies were searched in PubMed, Embase, and the Cochrane Library up to June 2023. Efficacy was evaluated by intention-to-treat analysis. Data were combined by meta-analyzing risk differences (RD). Heterogeneity was evaluated by subgrouping. RESULTS: Seventy-seven studies (24 randomized clinical trials) evaluated 44,162 patients (22,297 receiving VPZ and 21,865 PPIs). Overall VPZ efficacy was 88% (95% CI = 87%-90%): 86%, 88%, and 94% for dual/triple/quadruple-VPZ-containing therapies. VPZ efficacy was 87% (86%-89%) in first-line and 90% (87%-93%) in rescue therapy. VPZ performed better than PPIs in treatment-naïve patients (87% vs. 70%; RD = 0.13, 95% CI = 0.11-0.15) and when using triple regimens. No significant differences were observed in rescue and quadruple therapies. In patients with clarithromycin-resistant infection, VPZ-based therapies demonstrated an 81% efficacy (76%-85%), surpassing PPIs (76% vs. 40%; RD = 0.33, 95% CI = 0.24-0.43). For clarithromycin-susceptible strains, VPZ efficacy was 92% (89%-95%), similar to PPIs. VPZ adverse events rate was 19% (16%-21%), comparable to PPI-based regimens (18% vs. 13%, respectively; RD = 0.00, 95% CI = -0.01 to 0.02, p = 0.57). CONCLUSIONS: The efficacy of VPZ-based regimens was over 85% in all treatment combinations. In treatment-naïve and clarithromycin-resistant patients, VPZ performed better than PPIs. In rescue therapy, in clarithromycin-susceptible patients or when quadruple regimens were prescribed, this advantage was not confirmed. Tolerability was similar in both regimens.