The Wolfson Centre for Personalised Medicine, Department of Molecular & Clinical Pharmacology, University of Liverpool, Block A: Waterhouse Buildings, 1-5 Brownlow Street, Liverpool, L69 3GL, UK.
Pharmacogenomics. 2014 Apr;15(6):857-68. doi: 10.2217/pgs.14.65.
Antiepileptic drugs can induce potentially life-threatening hypersensitivity reactions such as Stevens-Johnson syndrome at a frequency of one in 10,000 to one in 1000 treated patients. There is a considerable cross-reactivity among different antiepileptic drugs but the mechanisms are not known. In this review we have summarized current evidence on antiepileptic drug-induced hypersensitivity reactions and performed meta-analyses of published case-control studies that investigated associations between HLA alleles and several antiepileptic drugs in diverse populations. As the heterogeneity between studies was high, we conducted subsequent subgroup analyses and showed that HLA-B*15:02 was associated with carbamazepine, lamotrigine and phenytoin-induced Stevens-Johnson syndrome in Asian populations indicating that pretreatment testing may prevent cross-reactivity. Additionally, we explored the potential of new, high-throughput technologies that may help to understand the mechanisms and predict the risk of adverse drug reactions in the future.
抗癫痫药物可引起潜在危及生命的过敏反应，如史蒂文斯-约翰逊综合征，其频率为每 10000 至 1000 名治疗患者中 1 例。不同的抗癫痫药物之间存在相当大的交叉反应，但机制尚不清楚。在这篇综述中，我们总结了抗癫痫药物引起的过敏反应的现有证据，并对已发表的病例对照研究进行了荟萃分析，这些研究调查了不同人群中 HLA 等位基因与几种抗癫痫药物之间的关联。由于研究之间的异质性很高，我们进行了后续的亚组分析，并表明 HLA-B*15:02 与卡马西平、拉莫三嗪和苯妥英钠引起的亚洲人群史蒂文斯-约翰逊综合征相关，表明预处理检测可能预防交叉反应。此外，我们还探讨了新的高通量技术的潜力，这些技术可能有助于我们在未来理解机制和预测药物不良反应的风险。
