Carbamazepine-Induced Toxic Effects and HLA-B*1502 Screening in Taiwan
Carbamazepine-Induced Toxic Effects and HLA-B*1502 Screening in Taiwan
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DOI：
10.1056/nejmoa1009717
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发表时间：
2011-03-24
影响因子：
158.5
通讯作者：
Shen, Chen-Yang
中科院分区：
文献类型：
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作者：
Chen, Pei;Lin, Juei-Jueng;Shen, Chen-Yang
背景卡马西平是一种抗惊厥药和情绪稳定药，是东南亚国家史蒂文斯-约翰逊综合征（SJS）及其相关疾病中毒性表皮坏死松解症（TEN）的主要原因。卡马西平诱导的 SJS-TEN 与 HLA B* 1502 等位基因密切相关。我们试图通过使用 HLA-B*1502 筛查前瞻性地识别具有该疾病遗传风险的受试者来预防卡马西平诱发的 SJS-TEN。方法我们从台湾 23 家医院招募了 4877 名未服用卡马西平的候选受试者。我们对从受试者外周血中纯化的 DNA 进行基因分型，以确定他们是否携带 HLA-B*1502 等位基因。 HLA-B*1502 检测呈阳性的患者（占总数的 7.7%）被建议不要服用卡马西平，并给予替代药物或建议继续服用研究前药物；检测结果呈阴性的患者（92.3%）被建议服用卡马西平。我们在两个月内每周一次通过电话采访受试者，以监测他们的症状。我们使用估计的 SJS-TEN 历史发病率作为对照。 结果 4.3% 的受试者出现轻微、短暂的皮疹； 0.1% 的受试者出现更广泛的皮疹，并住院治疗。 SJS-TEN 在任何接受卡马西平的 HLA-B*1502 阴性受试者中均未发育。相比之下，卡马西平诱发的 SJS-TEN 的估计历史发生率 (0.23%) 将转化为研究对象中大约 10 例 (P
BACKGROUNDCarbamazepine, an anticonvulsant and a mood-stabilizing drug, is the main cause of the Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), in Southeast Asian countries. Carbamazepine-induced SJS-TEN is strongly associated with the HLA B* 1502 allele. We sought to prevent carbamazepine- induced SJS-TEN by using HLA-B*1502 screening to prospectively identify subjects at genetic risk for the condition.METHODSFrom 23 hospitals in Taiwan, we recruited 4877 candidate subjects who had not taken carbamazepine. We genotyped DNA purified from the subjects' peripheral blood to determine whether they carried the HLA-B*1502 allele. Those testing positive for HLA-B*1502 (7.7% of the total) were advised not to take carbamazepine and were given an alternative medication or advised to continue taking their prestudy medication; those testing negative (92.3%) were advised to take carbamazepine. We interviewed the subjects by telephone once a week for 2 months to monitor them for symptoms. We used the estimated historical incidence of SJS-TEN as a control.RESULTSMild, transient rash developed in 4.3% of subjects; more widespread rash developed in 0.1% of subjects, who were hospitalized. SJS-TEN did not develop in any of the HLA-B*1502-negative subjects receiving carbamazepine. In contrast, the estimated historical incidence of carbamazepine-induced SJS-TEN (0.23%) would translate into approximately 10 cases among study subjects (P