J Pharm Pharm Sci. 2010;13(4):615-25. doi: 10.18433/j3wk5s.
Functional polymorphisms of the UGT1A1 gene, particularly the UGT1A128 variant, are associated with the severity of the bone marrow suppression in patients with metastatic colorectal cancer receiving irinotecan. This study assesses the cost-effectiveness of screening for UGT1A128 polymorphism associated with primary prophylactic Granulocytes Colony Stimulating Factor in patients homozygous for the *28 allele. The effectiveness was estimated based on the number of neutropenia avoided.
We modelled a theoretical population treated with combined 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) for metastatic colorectal cancer. A decision tree simulated the health outcomes, measured by the prevalence of neutropenic events for two strategies, with or without UGT1A1 genotype screening. The model incorporated direct hospital costs and was validated with a sensitivity analysis. We calculated the cost-effectiveness ratio: CE=∆C / ∆E = "genotyping" cost - "no genotyping" cost / number of febrile neutropenia avoided.
In the "genotyping strategy", the cost to avoid one febrile neutropenia event per 1000 patients treated was € 942.8 to € 1090.1. The sensitivity analysis showed a better CE ratio of € 733.4 to € 726.6 per febrile neutropenic event avoided.
UGT1A1 genotype screening before irinotecan treatment is a cost-efficient strategy for the hospital. Systematic genotyping prior to chemotherapy, and administration of CSF in patients homozygotes for the *28 allele allow to avoid 91 febrile neutropenias at an acceptable cost.
UGT1A1 基因的功能多态性,特别是 UGT1A128 变体,与接受伊立替康的转移性结直肠癌患者骨髓抑制的严重程度相关。本研究评估了针对 UGT1A128 多态性进行筛查,以对 UGT1A1*28 等位基因纯合子患者进行预防性粒细胞集落刺激因子(Granulocytes Colony Stimulating Factor,简称 G-CSF)的成本效益。有效性是基于避免中性粒细胞减少症的数量来估计的。
我们建立了一个理论人群模型,这些患者接受氟尿嘧啶、亚叶酸钙和伊立替康(FOLFIRI)联合治疗转移性结直肠癌。决策树模拟了两种策略的健康结果,一种是有 UGT1A1 基因型筛查的策略,另一种是没有 UGT1A1 基因型筛查的策略。该模型纳入了直接的医院成本,并通过敏感性分析进行了验证。我们计算了成本效益比(CE):CE=∆C / ∆E = “基因分型”成本-“无基因分型”成本/避免的发热性中性粒细胞减少症的数量。
在“基因分型策略”中,每 1000 名接受治疗的患者中避免一次发热性中性粒细胞减少症的成本为 942.8 至 1090.1 欧元。敏感性分析显示,每避免一次发热性中性粒细胞减少症的成本效益比为 733.4 至 726.6 欧元。
在伊立替康治疗前进行 UGT1A1 基因分型是一种对医院具有成本效益的策略。在化疗前进行系统的基因分型,并对 UGT1A1*28 等位基因纯合子患者给予 G-CSF,可以以可接受的成本避免 91 例发热性中性粒细胞减少症。