AUTHOR=Morino Yuko , Sugimoto Mitsushige , Nagata Naoyoshi , Niikiura Ryota , Iwata Eri , Hamada Mariko , Kawai Yusuke , Fujimiya Tatsuhiro , Takeuchi Hironori , Unezaki Sakae , Kawai Takashi 

TITLE=Influence of Cytochrome P450 2C19 Genotype on Helicobacter pylori Proton Pump Inhibitor-Amoxicillin-Clarithromycin Eradication Therapy: A Meta-Analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.759249

DOI=10.3389/fphar.2021.759249

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Proton pump inhibitors (PPIs) are the first-line treatment for acid-related diseases. The pharmacokinetics and therapeutic efficacy of PPIs, however, are influenced by genetic factors such as variants in genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19 [CYP2C19]) and drug transporters. We performed a meta-analysis to evaluate the influence of CYP2C19 genotype and PPI class, PPI dose, treatment duration and clarithromycin dose on the cure rate of PPI-containing <italic>Helicobacter pylori</italic> eradication therapy.</p><p><bold>Methods:</bold> Randomized control trials (RCTs) investigating cure rates using a PPI-amoxicillin-clarithromycin regimen among different CYP2C19 genotypes through May 2021 were included.</p><p><bold>Results:</bold> A total of 25 studies (5,318 patients) were included. The overall eradication rate in the intention-to-treat analysis was 79.0% (3,689/4,669, 95% confidence interval [CI]: 77.8–80.2%), and that in CYP2C19 extensive metabolizers (EMs), intermediate metabolizer (IMs) and poor metabolizers (PMs) was 77.7% (1,137/1,464, 95% CI: 75.3–79.6%), 81.2% (1,498/1,844, 95% CI: 79.3–83.0%) and 86.8% (644/742, 95% CI: 83.9–88.9%), respectively. Meta-analysis showed that the relaTakashitive risk of failed eradication in CYP2C19 EMs compared with IMs and PMs was 1.21 (95% CI: 1.06–1.39, <italic>P</italic> = 0.006) and 1.57 (95% CI: 1.27–1.94, <italic>P</italic> &lt; 0.001), respectively, in the fixed-effects model. The cure rate of omeprazole and lansoprazole-containing eradication regimens differed among CYP2C19 genotypes (<italic>P</italic> &lt; 0.05), while that of rabeprazole and esomeprazole-containing regimens was similar.</p><p><bold>Conclusion:</bold> The cure rates of PPI-amoxicillin-clarithromycin <italic>H. pylori</italic> eradication regimen, especially those containing omeprazole and lansoprazole, differ among CYP2C19 genotypes. Therefore, selection of a second-generation PPI or tailored treatment may achieve higher eradication rates than first-generation PPI-amoxicillin-clarithromycin triple regimen.</p>