Cytochrome P450 2C19 (CYP2C19) genotype status is not associated with cure rates of dual therapy with rabeprazole and amoxicillin for Helicobacter pylori

Background: Proton pump inhibitors (PPIs) are the first-line treatment for acid-related diseases. The pharmacokinetics and therapeutic efficacy of PPIs, however, are influenced by genetic factors such as variants in genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19 [CYP2C19]) and drug transporters. We performed a meta-analysis to evaluate the influence of CYP2C19 genotype and PPI class, PPI dose, treatment duration and clarithromycin dose on the cure rate of PPI-containing Helicobacter pylori eradication therapy.Methods: Randomized control trials (RCTs) investigating cure rates using a PPI-amoxicillin-clarithromycin regimen among different CYP2C19 genotypes through May 2021 were included.Results: A total of 25 studies (5,318 patients) were included. The overall eradication rate in the intention-to-treat analysis was 79.0% (3,689/4,669, 95% confidence interval [CI]: 77.8–80.2%), and that in CYP2C19 extensive metabolizers (EMs), intermediate metabolizer (IMs) and poor metabolizers (PMs) was 77.7% (1,137/1,464, 95% CI: 75.3–79.6%), 81.2% (1,498/1,844, 95% CI: 79.3–83.0%) and 86.8% (644/742, 95% CI: 83.9–88.9%), respectively. Meta-analysis showed that the relaTakashitive risk of failed eradication in CYP2C19 EMs compared with IMs and PMs was 1.21 (95% CI: 1.06–1.39, P = 0.006) and 1.57 (95% CI: 1.27–1.94, P < 0.001), respectively, in the fixed-effects model. The cure rate of omeprazole and lansoprazole-containing eradication regimens differed among CYP2C19 genotypes (P < 0.05), while that of rabeprazole and esomeprazole-containing regimens was similar.Conclusion: The cure rates of PPI-amoxicillin-clarithromycin H. pylori eradication regimen, especially those containing omeprazole and lansoprazole, differ among CYP2C19 genotypes. Therefore, selection of a second-generation PPI or tailored treatment may achieve higher eradication rates than first-generation PPI-amoxicillin-clarithromycin triple regimen.

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Abstract P241: One-Year Cost-Effectiveness of Cytochrome P450 2C19 Genotype-Guided Antiplatelet Therapy in Patients With Acute Coronary Syndromes

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.4.suppl_1.ap241 ◽

2011 ◽

Vol 4 (suppl_1) ◽

Author(s):

Scott L Charland ◽

Barnabie C Agatep ◽

Daniel C Malone ◽

Eric J Stanek

Keyword(s):

Cytochrome P450 ◽

Cost Effectiveness ◽

Antiplatelet Therapy ◽

Annual Cost ◽

Extensive Metabolizers ◽

Cyp2c19 Genotype ◽

Event Management ◽

Test Cost ◽

Cytochrome P450 2C19 ◽

The Cost

OBJECTIVES: Cytochrome P450 2C19 (CYP2C19) genotype has been shown to affect cardiovascular (CV) outcomes for clopidogrel but not prasugrel. This study evaluates the cost-effectiveness of CYP2C19-guided vs. routine antiplatelet therapy in ACS patients. METHODS: We constructed a literature-based, decision analytic, Markov model (TreeAge 2009) to estimate the cost-effectiveness of CYP2C19-guided aspirin plus either clopidogrel or prasugrel therapy vs. no genotyping. Post-initial ACS CV events were based on the TRITON-TIMI 38 study and related costs were derived primarily using 2007 Healthcare Cost and Utilization Project DRGs for nonfatal MI and stroke, CV death, intracranial hemorrhage, other life-threatening bleed, and minor bleed. Additional costs and disease-state utilities were obtained from other published sources. All costs were adjusted to 2009 $US using the Consumer Price Index medical care component. The model allowed for clopidogrel/prasugrel discontinuation and aspirin monotherapy. Model sensitivity was assessed using 1-way and multi-way analysis of influential parameters. RESULTS: The base case model demonstrated that CYP2C19 genotype guided antiplatelet therapy yielded lower overall annual cost and greater efficacy vs. no genotyping ( Table ). The model was sensitive to (in declining order): clopidogrel cost/day ($1 to $5.78), prasugrel cost/day ($4.09 to $ 6.81), % CYP2C19 extensive metabolizers on clopidogrel (60% to 100%), CYP2C19 test cost ($60 to $250), and monthly CV event management cost. A threshold value for clopidogrel at <$2.14/day favored the no genotyping strategy. However, the genotyping strategy was dominant when clopidogrel cost =$1/day and a CYP2C19 test cost threshold of <$125 on 2-way analysis. CONCLUSIONS: CYP2C19 genotype-guided clopidogrel or prasugrel therapy is cost-effective for up to 1 year in ACS patients, and can remain a preferred strategy at a hypothetical generic clopidogrel cost of $1.00/day. Table Strategy1 Annual Cost Incremental Cost Quality Adjusted Life Year (QALY) Incremental QALY Cost/QALY Incremental Cost Effectiveness (ICER) CYP2C19 Genotype-Guided $ 3,211 0.7212 $ 4,452 No Gentoyping $ 3,331 $120 0.6767 - (0.0445) $ 4,921 (Dominated) 1Base case values:Drug wholesale acquisition cost/day: clopidogrel $4.62, prasugrel $5.45; Baseline post-ACS utility = 0.83; Monthly cost for post-CV event management = $351; CYP2C19 genotyping =$185; After genotyping: 80% of extensive metabolizers, 20% of intermediate metabolizers and 10% of poor metabolizers on clopidogrel; 80% on clopidogrel without genotyping; Willingness to pay = $200

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CYP2C19 genotype status and dual therapy with omeprazole and amoxicillin for eradication of Helicobacter pylori and peptic ulcer healing

Gastroenterology ◽

10.1016/s0016-5085(98)80517-9 ◽

1998 ◽

Vol 114 ◽

pp. A127

Author(s):

Takahisa Furuta ◽

Kyoichi Ohashi ◽

Takashi Kamata ◽

Misako Takashima ◽

Hiroyuki Hanai ◽

...

Keyword(s):

Helicobacter Pylori ◽

Peptic Ulcer ◽

Ulcer Healing ◽

Dual Therapy ◽

Cyp2c19 Genotype

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Incidence of Drug Interaction When Using Proton Pump Inhibitor and Warfarin According to Cytochrome P450 2C19 (CYP2C19) Genotype in Japanese

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0034-1383814 ◽

2014 ◽

Vol 63 (01) ◽

pp. 045-050 ◽

Cited By ~ 4

Author(s):

Motomi Shiono ◽

Kenji Akiyama ◽

Akira Sezai ◽

Shinji Wakui ◽

Haruka Kimura ◽

...

Keyword(s):

Cytochrome P450 ◽

Drug Interaction ◽

Proton Pump Inhibitor ◽

Proton Pump ◽

Cyp2c19 Genotype ◽

Cytochrome P450 2C19

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Effect of Drug Combination on Omeprazole Metabolism by Cytochrome P450 2C19 in Helicobacter pylori Eradication Therapy

Chemical and Pharmaceutical Bulletin ◽

10.1248/cpb.c19-00084 ◽

2019 ◽

Vol 67 (8) ◽

pp. 810-815

Author(s):

Tamer Z. Attia ◽

Taku Yamashita ◽

Hirofumi Tsujino ◽

Sayed M. Derayea ◽

Yasuo Tsutsumi ◽

...

Keyword(s):

Helicobacter Pylori ◽

Cytochrome P450 ◽

Drug Combination ◽

Eradication Therapy ◽

Cytochrome P450 2C19

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Abstract TP411: Effects of Triflusal and Clopidogrel in Secondary Prevention of Stroke Based on Cytochrome P450 2C19 Genotyping

Stroke ◽

10.1161/str.48.suppl_1.tp411 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Kyung-Yul Lee ◽

Sang Won Han ◽

Yong-Jae Kim ◽

Seong Hwan Ahn ◽

Woo-Keun Seo ◽

...

Keyword(s):

Cytochrome P450 ◽

Secondary Prevention ◽

Recurrent Stroke ◽

Tertiary Care ◽

Antiplatelet Agents ◽

Stroke Recurrence ◽

Cyp2c19 Genotype ◽

Open Label ◽

Genotype Group ◽

Cytochrome P450 2C19

Background: The relationship between stroke recurrence and cytochrome P450 2C19 (CYP2C19) genotype for the secondary prevention of ischemic stroke (IS) is not clearly defined. We investigated the effect of antiplatelet agents based on CYP2C19 genotype in secondary prevention of IS. Methods: In this prospective, multicenter, randomized, parallel-group, open-label, and blind genotype trial, we enrolled first non-cardiogenic IS patients within 30 days prior to screening at the 18 tertiary-care hospitals. Participants received 300 mg triflusal twice a day or 75 mg clopidogrel once daily. CYP2C19 genotyping was done in all patients and genotype results were blind during the study. The primary outcome was the time from randomization to first recurrent IS or hemorrhagic stroke. Efficacy analyses were performed using both the modified intention-to- treat population and the per-protocol population. The study is registered with ClinicalTrials.gov (NCT01174693). Results: This trial failed to meet its recruitment goal due to slow enrollment. A total of 784 (73% of required sample size) patients were followed for a mean of 2.5 years. In poor CYP2C19 genotype group (n=484), 30 (6.2%) patients had a recurrent stroke. The risk of recurrent stroke in triflusal group was 2.9% per year and was not significantly different with clopidogrel group (2.2% per year; hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.6 to 2.53). In clopidogrel treatment group (n=393), 20 (5.1%) had a recurrent stroke. The risk of recurrent stroke in good CYP2C19 genotype was 1.6% per year and was not significantly different with poor genotype (2.2% per year; HR, 0.69; 95% CI, 0.26 to 1.79). Conclusions: In poor CYP2C19 genotype group, either triflusal or clopidogrel was not superior to the other in the prevention of recurrent stroke.

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