Pharmacogenomics-based Tailored Versus Standard Therapeutic Regimen for Eradication of H. pylori

Abstract

Helicobacter pylori eradication rates by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin at standard doses depend on bacterial susceptibility to clarithromycin and patient CYP2C19 genotypes. We examined the usefulness of a personalized therapy for H. pylori infection based on these factors as determined by genetic testing. First, optimal lansoprazole dosing schedules that would achieve sufficient acid inhibition to allow H. pylori eradication therapy in each of different CYP2C19 genotype groups were determined by a 24-h intragastric pH monitoring. Next, 300 H. pylori-positive patients were randomly assigned to the standard regimen group (lansoprazole 30 mg twice daily (b.i.d.)), clarithromycin 400 mg b.i.d., and amoxicillin 750 mg b.i.d. for 1 week) or the tailored regimen group based on CYP2C19 status and bacterial susceptibility to clarithromycin assessed by genetic testing. Patients with failure of eradication underwent the second-line regimen. The per-patient cost required for successful eradication was calculated for each of the groups. In the first-line therapy, the intention-to-treat eradication rate in the tailored regimen group was 96.0% (95% CI=91.5-98.2%, 144/150), significantly higher than that in the standard regimen group (70.0%: 95% CI=62.2-77.2%, 105/150) (P<0.001). Final costs per successful eradication in the tailored and standard regimen groups were $669 and $657, respectively. In conclusion, the pharmacogenomics-based tailored treatment for H. pylori infection allowed a higher eradication rate by the initial treatment without an increase of the final per-patient cost for successful eradication. However, the precise cost-effectiveness of this strategy remains to be determined.

New concepts of resistance in the treatment of Helicobacter pylori infections

“…As might be expected, these CYP2C19 genotypic differences in pharmacokinetics and pharmacodynamics of PPIs are reflected in factors such as healing of erosive esophagitis and eradication rates for H. pylori infection using PPI-containing regimens 30 . The majority of studies have come from Asia where poor metabolizers are relatively common.…”

“…Genotypic differences also play an important role in therapeutic success 30 . Cytochrome P450 (CYP) 2C19 is a polymorphic enzyme metabolizing proton pump inhibitors such as omeprazole, lansoprazole and rabeprazole and differences in PPI metabolism have provided critical insights into how to achieve more effective therapy [31][32][33] .…”

“…Plasma PPI levels and intragastric pHs during PPI treatment in the RM group are lowest, those in the IM group come next, and those in the PM group are highest among the three groups. Eradication rates with triple therapy are inversely related to the ability to metabolize the PPIs (ie the RM group has lower eradication rate compared to other groups) 30,[33][34][35][36][37][38] .…”

Personalized treatment in the eradication therapy for Helicobacter pylori

“…Amplification at 68˚C for 2 min was then performed and the bands of PCR products were verified by ethidium bromide staining after 3% agarose gel electrophoresis. Primers were designed so that the 320 bp band was observed with the 2142A and 2143A wild-types and the 238 bp band was observed with the 2142G or 2143G mutations (Table I) (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

“…However, the eradication failure rate with this method was about 30%. Individual variability in CAM-resistant HP and PPI metabolism are important factors in this failure rate (2)(3)(4)(5)(6)(7).…”