Why the Vonoprazan Helicobacter pylori Therapies in the US-European Trial Produced Unacceptable Cure Rates.

ABSTRACT

INTRODUCTION: Helicobacter pylori infects a large percentage of the world's population and is etiologically related to gastric cancer. The U.S. Food and Drug Administration recently approved two 14-day vonoprazan-containing regimens (vonoprazan-amoxicillin with or without clarithromycin) for H. pylori infections in the United States/Europe. METHODS: We critically reviewed the trial methods to discover why the results were unacceptable low [i.e., no regimen achieved clinically acceptable (≥ 90%) or even conditionally acceptable cure rates (≥ 85%)]. Cure rates with antibiotic susceptible strains were 84.7 for vonoprazan triple therapy, 78.5 for vonoprazan-amoxicillin, and 78.7 for lansoprazole triple therapy, respectively. As was previously shown in Japan, the benefit from adding clarithromycin to vonoprazan-amoxicillin was minimal and the majority of the clarithromycin administered was unnecessary. RESULTS: The possible reasons for failure to achieve high cure rates discussed include (a) reduced intragastric antibiotic concentrations, (b) an increase in heteroresistance, and (c) failure to achieve an intragastric pH conducive for amoxicillin to eradicate the infection. In addition, there was no pilot study or other attempt to optimize any regimen. CONCLUSION: The most likely reason for failure was failure to achieve high intragastric concentrations of antibiotics or to achieve an intragastric pH conducive for amoxicillin to be active. Importantly, vonoprazan triple therapy resulted in > 10 tons of unneeded clarithromycin/million courses of vonoprazan triple therapy. Antibiotic misuse combined with low cure rates suggest that vonoprazan-clarithromycin triple therapies should not be prescribed for H. pylori infection. Dual vonoprazan-amoxicillin therapy has proven effective elsewhere and after optimization may eventually prove useful in the U.S./Europe.