Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine, Seoul, South Korea.
Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul, South Korea.
Clin Transl Sci. 2024 Mar;17(3):e13772. doi: 10.1111/cts.13772.
Genetic variants affect drug responses, making pre-emptive genotyping crucial for averting serious adverse events (SAEs) and treatment failure. However, assessing the benefits of pre-emptive genotyping based on genetic distribution, drug exposure, and demographics is challenging. This study aimed to estimate the population-level benefits of pre-emptive genotyping in the Korean population using nationwide cohort data. We reviewed actionable gene-drug combinations recommended by both the Clinical Pharmacogenomics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) as of February 2022, identifying high-risk phenotypes. We collected reported risk reduction from genotyping and standardized it into population attributable risks. Healthcare reimbursement costs for SAEs and treatment failures were obtained from the Health Insurance Review and Assessment Service Statistics in 2021. The benefits of pre-emptive genotyping for a specific group were determined by multiplying drug exposure from nationwide cohort data by individual genotyping benefits. We identified 31 gene-drug-event pairs, with CYP2D6 and CYP2C19 demonstrating the greatest benefits for both male and female patients. Individuals aged 65-70 years had the highest individual benefit from pre-emptive genotyping, with $84.40 for men and $100.90 for women. Pre-emptive genotyping, particularly for CYP2D6 and CYP2C19, can provide substantial benefits.
遗传变异会影响药物反应，因此，预先进行基因分型对于避免严重不良事件 (SAEs) 和治疗失败至关重要。然而，基于遗传分布、药物暴露和人口统计学评估预先基因分型的益处具有挑战性。本研究旨在使用全国性队列数据来估计预先基因分型在韩国人群中的人群获益。我们回顾了截至 2022 年 2 月临床药物基因组学实施联盟 (CPIC) 和荷兰药物基因组学工作组 (DPWG) 推荐的可操作基因-药物组合，确定了高风险表型。我们收集了基因分型降低风险的报告，并将其标准化为人群归因风险。2021 年从健康保险审查和评估服务统计数据中获得了 SAEs 和治疗失败的医疗保健报销费用。通过将全国性队列数据中的药物暴露乘以个体基因分型获益，确定了特定群体预先基因分型的获益。我们确定了 31 个基因-药物-事件对，CYP2D6 和 CYP2C19 对男性和女性患者都具有最大的获益。65-70 岁的个体从预先基因分型中获益最大，男性为 84.40 美元，女性为 100.90 美元。预先基因分型，特别是 CYP2D6 和 CYP2C19，可以带来显著的获益。
