Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan

Pei Chen, Juei Jueng Lin, Chin Song Lu, Cheung Ter Ong, Peiyuan F. Hsieh, Chih Chao Yang, Chih Ta Tai, Shey Lin Wu, Cheng Hsien Lu, Yung Chu Hsu, Hsiang Yu Yu, Long Sun Ro, Chung Ta Lu, Chun Che Chu, Jing Jane Tsai, Yu Hsiang Su, Sheng Hsing Lan, Sheng Feng Sung, Shu Yi Lin, Hui Ping ChuangLi Chen Huang, Ying-Ju Chen, Pei Joung Tsai, Hung Ting Liao, Yu Hsuan Lin, Chien Hsiun Chen, Wen-Hung Chung, Shuen Iu Hung, Jer Yuarn Wu, Chi-Feng Chang, Luke Chen, Yuan Tsong Chen, Chen Yang Shen, Chaur-Jong Hu

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Abstract

BACKGROUND: Carbamazepine, 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. METHODS: From 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. RESULTS: Mild, 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<0.001). CONCLUSIONS: The identification of subjects carrying the HLA-B*1502 allele and the avoidance of carbamazepine therapy in these subjects was strongly associated with a decrease in the incidence of carbamazepine-induced SJS-TEN.

Original languageEnglish
Pages (from-to)1126-1133
Number of pages8
JournalNew England Journal of Medicine
Volume364
Issue number12
DOIs
Publication statusPublished - Mar 24 2011

ASJC Scopus subject areas

  • Medicine(all)

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    Chen, P., Lin, J. J., Lu, C. S., Ong, C. T., Hsieh, P. F., Yang, C. C., Tai, C. T., Wu, S. L., Lu, C. H., Hsu, Y. C., Yu, H. Y., Ro, L. S., Lu, C. T., Chu, C. C., Tsai, J. J., Su, Y. H., Lan, S. H., Sung, S. F., Lin, S. Y., ... Hu, C-J. (2011). Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. New England Journal of Medicine, 364(12), 1126-1133. https://doi.org/10.1056/NEJMoa1009717