Rapid metabolizer genotype of CYP2C19 is a risk factor of being refractory to proton pump inhibitor therapy for reflux esophagitis

Background: Proton pump inhibitors (PPIs) are mainly metabolized by cytochrome P450 2C19 (CYP2C19) and used as the first-line therapy for gastroesophageal reflux disease (GERD). However, while several studies have examined the influence of CYP2C19 polymorphism on GERD treatment with PPIs, most have had small sample sizes and were conducted in a single center. Here, we used meta-analysis to investigate whether or not the CYP2C19 rapid metabolizer (RM) genotype is a risk factor for GERD patients being refractory to PPI therapy.

Methods: PubMed and other electronic databases were systematically searched up to August 2014 using the following terms: "GERD and CYP2C19", "esophagitis and CYP2C19", and "non-erosive reflux disease and CYP2C19." Searches were limited to publications in English, and two investigators evaluated eligible studies and extracted data.

Results: The total efficacy rate of PPIs for GERD, including reflux esophagitis (RE) and non-erosive reflux disease, was 56.4% (95% confidence interval [CI]; 53.9-58.9%, 870/1543) in intention-to-treat analysis and 63.8% (95%CI; 61.3-66.2%, 950/1489) in per-protocol analysis. Efficacy rates varied significantly between CYP2C19 genotypes (intention-to-treat analysis: RMs, 52.2% [315/604]; intermediate metabolizers, 56.7% [298/526]; poor metabolizers [PMs], 61.3% [138/225]; P = 0.047). Among RE patients, CYP2C19 RMs had an increased risk of being refractory to PPI therapy compared with PMs (odds ratio: 1.661, 95% CI: 1.023-2.659, P = 0.040).

Conclusions: The present meta-analysis demonstrates that CYP2C19 RMs with RE have an increased risk of being refractory to PPI therapy compared with PMs. Individualized dosing regimen with PPIs based on CYP2C19 genotype might be a valid therapeutic strategy for overcoming insufficient gastric acid inhibition.