Supplementary Material for: Efficacy and safety of vonoprazan and amoxicillin dual therapy for Helicobacter pylori eradication: A systematic review and meta-analysis

Introduction: Vonoprazan, a novel potassium-competitive acid blocker, has a strong acid suppression effect and potent efficacy in acid-associated diseases, including Helicobacter pylori eradication. We performed a systematic review and meta-analysis to investigate the efficacy and safety of vonoprazan/amoxicillin dual therapy for Helicobacter pylori eradication. Methods: We conducted a systematic literature search through PubMed, Web of Science, EMBASE and the Cochrane Library up to June 2022, to identify randomized controlled trials and cohort studies comparing vonoprazan/amoxicillin dual therapy and triple therapies for Helicobacter pylori eradication. Primary outcomes were cure rates and relative efficacy. Secondary outcomes included adverse events, dropout rate and subgroup analysis. Results: Five studies with 1852 patients were included in the analysis. The cure rates of vonoprazan/amoxicillin dual therapy were 85.6% (95% CI: 79.7%-91.5%) and 88.5% (95% CI: 83.2%-93.8%) in the intention-to-treat and per-protocol analyses. The efficacy of vonoprazan/amoxicillin dual therapy was not inferior to that of triple therapy (intention-to-treat analysis: risk ratio (RR)=1.03, 95% CI: 0.97-1.10; per-protocol analysis: RR=1.02, 95% CI: 0.98-1.08); while it was significantly superior to the omeprazole or lansoprazole-based triple therapy (RR=1.15, 95% CI: 1.05-1.25, P=0.001). For clarithromycin-resistant strains, vonoprazan/amoxicillin dual therapy showed superiority to vonoprazan-based triple therapy (86.7% vs. 71.4%, RR=1.20, 95% CI: 1.03-1.39, P=0.02); however, vonoprazan/amoxicillin dual therapy was significant inferior to vonoprazan-based triple therapy for clarithromycin-sensitive strains (83.0% vs. 92.8%, RR=0.90, 95% CI: 0.85-0.95, P=0.0002). The adverse effects of vonoprazan/amoxicillin dual therapy were lower than those of triple therapy (21.2% vs. 26.5%, RR=0.86, 95% CI: 0.73-1.01, P=0.06), especially the incidence of diarrhea (P=0.01). Conclusions: The efficacy of vonoprazan/amoxicillin dual therapy is non-inferior to vonoprazan-based triple therapy but superior to the omeprazole or lansoprazole-based triple therapy, and has less side effects. Patients with clarithromycin-resistant strains are particularly expected to benefit from vonoprazan/amoxicillin dual therapy.