Effects of CYP2C19 Loss-of-Function Variants on the Eradication of H. pylori Infection in Patients Treated with Proton Pump Inhibitor-Based Triple Therapy Regimens: A Meta-Analysis of Randomized Clinical Trials

Abstract

BackgroundThere are inconsistent conclusions about whether CYP2C19 variants could affect H. pylori eradication rate in patients treated with the proton pump inhibitor (PPI)-based therapy. We therefore performed a meta-analysis of randomized clinical trials (RCTs) to re-evaluate the impact of CYP2C19 variants on PPI-based triple therapy for the above indication.MethodsAll relevant RCTs in the PubMed, Cochrane Library, EMBASE, Web of Science and two Chinese databases (up to February 2013) were systematically searched, and a pooled analysis was performed with the odds ratio (OR) and 95% confidence interval (CI) by the STATA software.ResultsSixteen RCT datasets derived from 3680 patients were included. There was no significant heterogeneity across the data available in this meta-analysis. There were significant differences in that rate between homozygous (HomEMs) and heterozygous (HetEMs) extensive metabolizers (OR 0.724; 95% CI 0.594–0.881), between HomEMs and poor metabolizers (PM) (OR 0.507; 95%CI 0.379–0.679), or between HetEMs and PMs (OR 0.688; 95%CI 0.515–0.920), regardless of the PPI being taken. Furthermore, sub-analysis of individual PPIs was carried out to explore the difference across all the PPIs used. A significantly low rate was seen in HomEMs vs. HetEMs taking either omeprazole (OR 0.329; 95%CI 0.195–0.553) or lansoprazole (OR 0.692; 95%CI 0.485–0.988), and also in HomEMs vs. PMs for omeprazole (OR 0.232; 95%CI 0.105–0.515) or lansoprazole (OR 0.441; 95%CI 0.252–0.771). However, there was no significant difference between HetEMs and PMs taking either one. No significant differences were observed for rabeprazole or esomeprazole across the CYP2C19 genotypes of interest.ConclusionsCarriage of CYP2C19 loss-of-function variants is associated with increased H. pylori eradication rate in patients taking PPI-based triple therapies when omeprazole or lansoprazole is chosen. However, there is no a class effect after use of rabeprazole or esomeprazole.

Antibiotic treatment forHelicobacter pylori: Is the end coming?

“…In addition, results of the subanalysis of the PPI type, omeprazole and lansoprazole were affected by CYP2C19 genotype. Unlike above, esomeprazole and rabeprazole were not affected by CYP2C19 genotype [145] . In studies published in Japan, esomeprazole and rabeprazole are less influenced by CYP2C19 genotype compared with another PPIs [146,147] .…”

“…According to a metaanalysis of a RCT in 2013, regardless of the PPI being taken, the eradication rates of PM were higher than HetEM and HomEM [145] . In addition, results of the subanalysis of the PPI type, omeprazole and lansoprazole were affected by CYP2C19 genotype.…”

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

“…That the genotype of CYP2C19 may affect the therapeutic outcomes of PPIs was demonstrated with a string of publications documenting lower intragastric pH 48,49,50 (Table 3) with diminished control of GERD symptoms 59,60,61, and lower eradication rates of H. pylori in patients with a NM phenotype status 62,63 (Table 4). As further evidence for the impact of genotype on therapeutic outcomes, Furuta et al 60.…”

“…One of the most informative analyses regarding the effect of genotype on H. pylori eradication comes from a 2013 meta-analysis that included data from 16 randomized controlled trials, in which patients were randomized to one of the H. pylori eradication regimens (N = 3680) [63]. The odds ratio of H. pylori eradication comparing NM to IM, and IM to PM were calculated.…”

Proton Pump Inhibitor Therapy in Eosinophilic Esophagitis: Current Role and Future Perspectives

“…. This genotype influences response to PPI therapy in PPI-based therapies, such as GERD or eradication therapy for Helicobacter pylori infection [42,43]. A rapid metabolizer genotype, which is the most common genotype in Caucasian populations (56-81 %), may result in low plasma levels and lack of therapeutic effect of PPI therapy in PP-REE patients, both in the short and long term.…”