Practical pharmacogenetics: the cost effectiveness of screening for thiopurine s-methyltransferase polymorphisms in patients with rheumatological conditions treated with azathioprine.
Practical pharmacogenetics: the cost effectiveness of screening for thiopurine s-methyltransferase polymorphisms in patients with rheumatological conditions treated with azathioprine.
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发表时间：
2002-12
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通讯作者：
C. Marra;J. Esdaile;A. Anis
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作者：
C. Marra;J. Esdaile;A. Anis
目的硫嘌呤甲基转移酶（TPMT）催化硫唑嘌呤（AZA）的失活，其基因多态性可导致10-15%的AZA剂量相关的严重毒性反应（主要是血液学细胞减少）。聚合酶链反应（PCR）检测提供了一种灵敏、特异的方法，可以在AZA治疗前前瞻性地识别这些患者，并通过减少剂量将毒性降至最低。我们的目的是模拟2种替代AZA治疗策略在风湿性疾病中的成本效益：（1）在AZA治疗前减少剂量，利用PCR确定导致TPMT缺陷的多态性;（2）不进行检测。该分析是从第三方付款人的角度进行的，为期一年。方法应用决策分析模型，绘制两种策略下患者的成本和结果。应用于模型的数据包括PCR的阳性和阴性预测值、AZA引起的不良事件的概率以及与其管理相关的成本。数据来源包括已发表的临床试验、诊断试验评价、监测试验和经济评价。结果剂量相关毒性导致AZA停药率为10- 20%。通常的给药策略每例患者花费677加元，而基因型导向的给药策略每例患者花费663加元。在基因型给药策略中，在6个月内避免一次不良事件所需治疗的数量为20。因此，基于基因型的给药策略主导了常规给药策略。单因素敏感性分析显示，对于成本、PCR检测的性质和不良事件的概率，估计值在+/- 30%的范围内是稳健的。结论：在AZA治疗前采用PCR检测TPMT多态性可能在某些医疗机构具有良好的价值。
OBJECTIVE Thiopurine S-methyltransferase (TPMT), which catalyzes the inactivation of azathioprine (AZA), exhibits genetic polymorphism that results in dose related, serious toxicities (mainly hematological cytopenias) in 10-15% of individuals treated with AZA. Polymerase chain reaction (PCR) tests provide a sensitive, specific means of prospectively identifying these patients before AZA therapy and minimizing toxicity through dosage reduction. Our objective was to model the cost effectiveness of the 2 alternative AZA treatment strategies in rheumatologic conditions: (1) utilizing PCR to determine polymorphisms leading to TPMT deficiencies prior to AZA therapy with a reduction in dose; and (2) no testing. The analysis was conducted from a third party payer perspective over one year. METHODS A decision analytic model was applied to map the costs and outcomes of patients under both strategies. Data applied to the model included the positive and negative predictive values of the PCR, the probabilities of adverse events due to AZA, and the costs associated with their management. Sources of data included published clinical trials, diagnostic test evaluations, surveillance trials, and economic evaluations. RESULTS Dose related toxicities resulted in AZA discontinuation rates of 10-20%. The usual dosing strategy cost $677 Cdn per patient, whereas the genotype directed dosing strategy cost $663 Cdn per patient. In the genotype dosing strategy, the number needed to treat to avoid one adverse event over 6 months was 20. Thus, the genotype based dosing strategy dominated the usual dosing strategy. One-way sensitivity analyses revealed that the estimates were robust to ranges of +/- 30% for the costs, the properties of the PCR test, and the probability of adverse events. CONCLUSION The introduction of PCR testing to identify TPMT polymorphisms prior to AZA treatment may represent good value in certain health care settings.