Litonius Kaisa, Kulla Noora, Falkenbach Petra, Kristiansson Kati, Tarkiainen E Katriina, Ukkola-Vuoti Liisa, Cajanus Kristiina, Korhonen Mari, Khan Sofia, Sistonen Johanna, Orpana Arto, Lindstedt Mats, Nyrönen Tommi, Perola Markus, Turpeinen Miia, Kytö Ville, Tornio Aleksi, Niemi Mikko
Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland.
Department of Clinical Pharmacology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland.
Clin Pharmacol Ther. 2025 Jan;117(1):278-288. doi: 10.1002/cpt.3458. Epub 2024 Oct 4.
Implementation of pharmacogenetic testing in clinical care has been slow and with few exceptions is hindered by the lack of real-world evidence on how to best target testing. In this retrospective register-based study, we analyzed a nationwide cohort of 1,425,000 patients discharged from internal medicine or surgical wards and a cohort of 2,178 university hospital patients for purchases and prescriptions of pharmacogenetically actionable drugs. Pharmacogenetic variants were obtained from whole genome genotype data for a subset (n = 930) of the university hospital patients. We investigated factors associated with receiving pharmacogenetically actionable drugs and developed a literature-based cost-benefit model for pre-emptive pharmacogenetic panel testing. In a 2-year follow-up, 60.4% of the patients in the nationwide cohort purchased at least one pharmacogenetically actionable drug, most commonly ibuprofen (25.0%) and codeine (19.4%). Of the genotyped subset, 98.8% carried at least one actionable pharmacogenetic genotype and 23.3% had at least one actionable gene-drug pair. Patients suffering from musculoskeletal or cardiovascular diseases were more prone to receive pharmacogenetically actionable drugs during inpatient episode. The cost-benefit model included frequently dispensed drugs in the university hospital cohort, comprising ondansetron (19.4%), simvastatin (7.4%), clopidogrel (5.0%), warfarin (5.1%), (es)citalopram (5.3%), and azathioprine (0.5%). For untargeted pre-emptive pharmacogenetic testing of all university hospital patients, the model indicated saving €17.49 in direct healthcare system costs per patient in 2 years without accounting for the cost of the test itself. Therefore, it might be reasonable to target pre-emptive pharmacogenetic testing to patient groups most likely to receive pharmacogenetically actionable drugs.
药物遗传学检测在临床护理中的实施进展缓慢，除少数情况外，由于缺乏关于如何最佳靶向检测的真实世界证据而受到阻碍。在这项基于回顾性登记的研究中，我们分析了内科或外科病房出院的142.5万名全国队列患者以及2178名大学医院患者购买和使用药物遗传学可作用药物的情况。药物遗传学变异来自大学医院部分患者（n = 930）的全基因组基因型数据。我们调查了与接受药物遗传学可作用药物相关的因素，并为预防性药物遗传学面板检测建立了基于文献的成本效益模型。在为期2年的随访中，全国队列中60.4%的患者购买了至少一种药物遗传学可作用药物，最常见的是布洛芬（25.0%）和可待因（19.4%）。在基因分型的子集中，98.8%的患者携带至少一种可作用的药物遗传学基因型，23.3%的患者有至少一对可作用的基因-药物对。患有肌肉骨骼或心血管疾病的患者在住院期间更倾向于接受药物遗传学可作用药物。成本效益模型包括大学医院队列中经常配发的药物，包括昂丹司琼（19.4%）、辛伐他汀（7.4%）、氯吡格雷（5.0%）、华法林（5.1%）、（艾司）西酞普兰（5.3%）和硫唑嘌呤（0.5%）。对于所有大学医院患者进行无针对性的预防性药物遗传学检测，该模型表明在不考虑检测本身成本的情况下，两年内每位患者可节省直接医疗系统成本17.49欧元。因此，将预防性药物遗传学检测靶向最有可能接受药物遗传学可作用药物的患者群体可能是合理的。
