Abstract
Background: 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 Helicobacter pylori eradication therapy. Methods: Randomized control trials (RCTs) investigating cure rates using a PPI-amoxicillin-clarithromycin regimen among different CYP2C19 genotypes through May 2021 were included. Results: 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, P = 0.006) and 1.57 (95% CI: 1.27–1.94, P < 0.001), respectively, in the fixed-effects model. The cure rate of omeprazole and lansoprazole-containing eradication regimens differed among CYP2C19 genotypes (P < 0.05), while that of rabeprazole and esomeprazole-containing regimens was similar. Conclusion: The cure rates of PPI-amoxicillin-clarithromycin H. pylori 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.
Highlights
The Maastricht V/Florence Consensus Report issued by the European Helicobacter Study Group in 2017 provides a guideline on how to manage Helicobacter pylori (H. pylori) infection (Malfertheiner et al, 2017)
Meta-analysis showed that the Relative risk (RR) of failed eradication in CYP2C19 extensive metabolizer of CYP2C19 (EM) compared with intermediate metabolizer of CYP2C19 (IM) and poor metabolizer of CYP2C19 (PM) was 1.21 and 1.57 in the fixed-effects model (Figures 1A,B and 1.44 in the randomeffects model (Supplementary Figure S2A and Supplementary S2B), respectively
Meta-analysis of studies that standard-dose-pump inhibitor (PPI) therapy showed that the RR of failed eradication in CYP2C19 EMs compared with IMs and PMs was 1.28 and 1.72, respectively
Summary
The Maastricht V/Florence Consensus Report issued by the European Helicobacter Study Group in 2017 provides a guideline on how to manage Helicobacter pylori (H. pylori) infection (Malfertheiner et al, 2017). In Japan, H. pylori eradication therapy is limited to regimens comprising an acid-inhibitory drug such as a PPI (e.g., esomeprazole, rabeprazole, lansoprazole and omeprazole) or vonoprazan at a standard dose at twice-daily dosing (bid), AMPC 750 mg bid, and CAM 200 mg or 400 mg bid for 7 days as a first-line regimen (Kato et al, 2019). This is despite the fact that eradication therapy for all H. pylori-positive patients with gastritis confirmed by endoscopy is currently covered by the Japanese National Health Insurance system. We performed a metaanalysis to evaluate the influence of CYP2C19 genotype and PPI class, PPI dose, treatment duration and clarithromycin dose on the cure rate of PPI-containing Helicobacter pylori eradication therapy
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