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基因多态性与钱包:细胞色素P450 2C19基因分型在根除与十二指肠溃疡相关的幽门螺杆菌感染中的成本效益

Polymorphisms and the pocketbook: the cost-effectiveness of cytochrome P450 2C19 genotyping in the eradication of Helicobacter pylori infection associated with duodenal ulcer.

作者信息

Lehmann David F, Medicis Joseph J, Franklin Patricia D

机构信息

SUNY Upstate Medical University, 750 E. Adams Street, Syracuse, NY 13210, USA.

出版信息

J Clin Pharmacol. 2003 Dec;43(12):1316-23. doi: 10.1177/0091270003259389.

Abstract

The clinical outcome of duodenal ulcer treated with proton pump inhibitor (PPI)-based, anti-Helicobacter pylori (H.p.) regimens varies according to cytochrome P450 2C19 (CYP2C19) genotype. CYP2C19 genotypes differ markedly in peoples of Pacific Rim descent compared with another ethnicity. The authors sought to determine the specific impact that these factors have on the cost-effectiveness of duodenal ulcer management. Their model consisted of two patient cohorts with Helicobacter pylori and duodenal ulcer, trichotomized into CYP2C19 homozygous extensive metabolizers (EMs), heterozygous EMs, and poor metabolizers (PMs), altering the anti-H.p. regimen in the genotyped cohort only. The authors took the perspective of a third-party payer, and the denominator was ulcer episode prevented. In the reference case, the use of CYP2C19 genotyping prior to initiating anti-H.p. therapy was dominant (costs were saved with each ulcer episode prevented) in all geographic regions of the United States. The subsequent break-even analysis showed a range of 89.20 dollars to 118.96 dollars--from Hawaii to the Midwest, respectively--required to eliminate the cost-savings from each genotype test performed. Using probabilities most unfavorable to genotyping, the variation of peoples with Pacific Rim origins from 0% to 100% altered the cost-effectiveness from 495 dollars to 2125 dollars per ulcer event prevented, respectively. The results suggest that treatment decisions for H.p. infection that are based on a patient's CYP2C19 genotype decreases expenses for health plans implementing testing. This analysis provides an economic basis to support recent calls to expand this technology into routine clinical care to prevent toxicity of narrow therapeutic index drugs.

摘要

基于质子泵抑制剂(PPI)的抗幽门螺杆菌(H.p.)方案治疗十二指肠溃疡的临床结果因细胞色素P450 2C19(CYP2C19)基因型而异。与其他种族相比,太平洋沿岸血统的人群中CYP2C19基因型存在显著差异。作者试图确定这些因素对十二指肠溃疡治疗成本效益的具体影响。他们的模型包括两个患有幽门螺杆菌和十二指肠溃疡的患者队列,根据CYP2C19纯合子广泛代谢者(EMs)、杂合子EMs和慢代谢者(PMs)分为三组,仅在基因分型队列中改变抗H.p.方案。作者采用第三方支付者的视角,分母为预防的溃疡发作次数。在参考案例中,在美国所有地理区域,在开始抗H.p.治疗前使用CYP2C19基因分型具有优势(每预防一次溃疡发作可节省成本)。随后的盈亏平衡分析表明,从夏威夷到中西部地区,分别消除每次基因检测节省的成本需要89.20美元至118.96美元。使用对基因分型最不利的概率,太平洋沿岸血统人群比例从0%到最高100%的变化,分别使每预防一次溃疡事件的成本效益从495美元变为2125美元。结果表明,基于患者CYP2C19基因型的H.p.感染治疗决策可降低实施检测的健康计划的费用。该分析提供了经济依据,支持最近将该技术扩展到常规临床护理以预防窄治疗指数药物毒性的呼吁。

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