High Potency Proton Pump Inhibitor Versus Vonoprazan in Helicobacter pylori Triple Therapy

BACKGROUND: The price of vonoprazan in the United States, as with many newly introduced drugs, is currently high. Here, we examined the cost-effectiveness of vonoprazan clarithromycin triple therapy for treatment of Helicobacter pylori in the United States. We compared cure rates and total treatment costs to achieve ≥ 90% cure with either vonoprazan or proton pump inhibitor (PPI) triple therapy. MATERIALS AND METHODS: We simulated a theoretical population and compared 4 scenarios comparing vonoprazan 20 mg twice daily or esomeprazole 40 mg twice daily. These included: (1) empiric vonoprazan versus esomeprazole clarithromycin triple therapy, (2) susceptibility-based vonoprazan versus esomeprazole clarithromycin triple therapy, (3) empiric vonoprazan versus esomeprazole clarithromycin triple therapy with treatment failures receiving bismuth quadruple therapy, and (4) susceptibility-based vonoprazan versus esomeprazole clarithromycin triple therapy with treatment failures receiving bismuth quadruple therapy. The prevalence of clarithromycin resistance was estimated at 30%. Cure rates were based on the H. pylori treatment nomogram and drug costs on U.S. 2025 retail prices (i.e., $50 for PPI and $960 for vonoprazan triple therapy). RESULTS: With 30% resistance, susceptibility-based therapy was the most effective (cure rate 92%). With empiric therapy, the cure rate with vonoprazan was higher than esomeprazole (88% vs. 77%) but overall costs increased 2.4-5.2 times. The cost per 1000 patients receiving vonoprazan was approximately $1000,000 versus $50,000 for esomeprazole. The least expensive, highly effective scenario was empiric esomeprazole triple therapy with treatment failures receiving bismuth quadruple therapy. CONCLUSIONS: Any treatment advantage of vonoprazan over PPI in clarithromycin triple therapy is restricted to those with clarithromycin resistance. Vonoprazan triple therapies cost 2 to 5 times more than a high potency PPI with small gains in cure rates. For susceptible infections, triple therapy using a high potency PPI should be preferred, and the most cost-effective strategy is to reserve vonoprazan for refractory cases.