CYP2C19 genotypes determine the efficacy of on-demand therapy of pantoprazole for reflux esophagitis as Los-Angeles grades C and D

Backgrounds and Aim: The present study determined whether the genotypes of S-mephenytoin 4′-hydroxylase (CYP2C19) could serve as an indicator to assess the success of long-term on-demand therapy (ODT) with pantoprazole for the patients with severe reflux esophagitis as Los Angles grade C or D (RE-CD). Methods: A total of 240 patients with RE-CD were prospectively enrolled to receive continuous pantoprazole, 40mg daily for 6months. The patients, who achieved complete healing and were free from acid reflux-related symptoms during follow up, were included to receive ODT with a 40mg pantoprazole tablet up to 1year. Each patient was followed to assess the monthly tablet number of 40mg pantoprazole and the cumulative rate of failure of ODT. The CYP2C19 genotype of each included patient was defined as homologous extensive metabolizer (HomoEM), heterologous extensive metabolizer (HeteroEM), and poor metabolizer (PM). Results: Two-hundred patients were included to receive ODT, including 51 as HomoEM, 108 as HeteroEM, and 41 as PM. There were no differences in demographic and endoscopic features among patients with different CYP2C19 genotypes (P>0.05). The 1-year cumulative failure rate of ODT was significantly higher in HomoEM than in HeteroEM and PM (P<0.05, by log-rank test). For those with successful ODT during the 1-year follow up, the mean monthly tablet number of pantoprazole was lower in PM than in HeteroEM and HomoEM (11.5 vs 16.3 and 18.6, P<0.05). Conclusion: For RE-CD with complete healing after continuous pantoprazole, the successful shift to ODT is determined by the CYP2C19 genotypes of the patients.