Chua Hui Min, Limenta Michael, Ng Carol Yee Leng, Lo Elaine Ah Gi
Department of Pharmacy, National University Hospital, Singapore, Singapore.
Vigilance and Compliance Branch, Health Products Regulation Group, Health Sciences Authority, Singapore, Singapore.
Am J Health Syst Pharm. 2025 Feb 20;82(5):e285-e293. doi: 10.1093/ajhp/zxae294.
To describe the implementation of human leukocyte antigen (HLA)-related genotype-guided prescribing in Singapore.
Various HLA alleles have been implicated in drug hypersensitivity syndromes (DHS). These include HLA-B15:02, which has been associated with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis, HLA-B58:01, which has been associated with increased risk of severe cutaneous adverse reactions with allopurinol use, and HLA-B*57:01, which has been associated with increased risk of hypersensitivity reactions with abacavir use. Integrating pharmacogenomics into patient care through genotype-guided prescribing potentially optimizes use of these drugs by reducing DHS-related and healthcare costs. We describe the prevalence of HLA-related DHS in Singapore, the cost-effectiveness of genotype-guided prescribing, and local policies and guidelines, as well as the impact of genotype-guided prescribing where available.
HLA-related genotype-guided prescribing has the potential to reduce the incidence of DHS and decrease healthcare costs, as seen in the success with carbamazepine. However, not all genotype-guided prescribing is cost-effective when implemented across the population, as was evident from local studies for allopurinol and abacavir. The cost-effectiveness of such measures may change over time with new data (eg, allele frequencies, test costs, drug prices, genotyping approach) and should be evaluated periodically and locally. Implementation of preemptive pharmacogenomics panel testing as part of routine clinical care may shift the threshold for cost-effectiveness and brings promise of further optimization of pharmacotherapy through precision medicine.
描述新加坡人类白细胞抗原（HLA）相关基因型指导下的处方用药实施情况。
多种HLA等位基因与药物超敏反应综合征（DHS）有关。这些包括HLA - B15:02，它与卡马西平诱发的史蒂文斯 - 约翰逊综合征/中毒性表皮坏死松解症有关；HLA - B58:01，它与使用别嘌醇时严重皮肤不良反应风险增加有关；以及HLA - B*57:01，它与使用阿巴卡韦时超敏反应风险增加有关。通过基因型指导下的处方用药将药物基因组学整合到患者护理中，有可能通过降低与DHS相关的费用和医疗成本来优化这些药物的使用。我们描述了新加坡HLA相关DHS的患病率、基因型指导下的处方用药的成本效益、当地政策和指南，以及在可行情况下基因型指导下的处方用药的影响。
正如卡马西平取得的成功那样，HLA相关基因型指导下的处方用药有潜力降低DHS的发生率并降低医疗成本。然而，从别嘌醇和阿巴卡韦的当地研究可以看出，并非所有基因型指导下的处方用药在整个人口中实施时都具有成本效益。随着新数据（如等位基因频率、检测成本、药物价格、基因分型方法）的出现，这些措施在不同时期的成本效益可能会发生变化，应定期在当地进行评估。作为常规临床护理的一部分实施预防性药物基因组学检测可能会改变成本效益的阈值，并有望通过精准医学进一步优化药物治疗。
