Rabeprazole Can Overcome the Impact of CYP2C19 Polymorphism on Quadruple Therapy

Abstract

The prospective study was designed to clarify the impact of CYP2C19 on quadruple therapies and survey the efficacies of rabeprazole-based quadruple therapy for Helicobacter pylori infection after failure of standard triple therapies. From January 2007 to March 2009, 1055 H. pylori-infected patients received standard triple regimens (proton-pump inhibitor (PPI), clarithromycin, and amoxicillin). Helicobacter pylori eradication was achieved in 865 (81.9%) subjects. One hundred ninety eradication-failure patients were enrolled and randomly assigned to receive a 7-day eradication therapy. Ninety-six patients were treated with esomeprazole-based quadruple rescue therapies (EB), while 94 patients were treated with rabeprazole-based quadruple rescue therapies (RB). Follow-up endoscopy was done 16 weeks later to assess the treatment response. Patients' responses, CYP2C19 genotypes, and antibiotics resistances were also examined. Intention-to-treat analysis revealed that RB had better eradication rates than EB (EB: 72.9%; 95% CI: 64.9-80.9% and RB: 78.7%; 95% CI 72.5-84.9%) (p value = .543). Per-protocol results were EB = 75.3%; 95% CI: 70.3-80.3% and RB = 85.1%; 95% CI: 80.6-89.6% (p value = .0401). Both regimens had similar compliance (p value = 0.155) and adverse events (p value = 0.219). We also surveyed those patients without resistance of any antibiotics. RB still showed better outcome than EB. Our data showed that esomeprazole-based regimen and CYP2C19 Hom EM genotype were important predictors for eradication failure. In quadruple therapy, rabeprazole-based regimens had better efficacy than esomeprazole-based regimens. CYP2C19 polymorphism also played an important role in quadruple therapy. It seems advisable to change PPI to rabeprazole in second-line quadruple therapy.