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

Research output: Contribution to journalArticle

422 Citations (Scopus)

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

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HLA-B Antigens
Poisons
Carbamazepine
Stevens-Johnson Syndrome
Taiwan
Alleles
Exanthema
Incidence
Telephone
Anticonvulsants

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chen, P., Lin, J. J., Lu, C. S., Ong, C. T., Hsieh, P. F., Yang, C. C., ... 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

Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. / Chen, Pei; Lin, Juei Jueng; Lu, Chin Song; Ong, Cheung Ter; Hsieh, Peiyuan F.; Yang, Chih Chao; Tai, Chih Ta; Wu, Shey Lin; Lu, Cheng Hsien; Hsu, Yung Chu; Yu, Hsiang Yu; Ro, Long Sun; Lu, Chung Ta; Chu, Chun Che; Tsai, Jing Jane; Su, Yu Hsiang; Lan, Sheng Hsing; Sung, Sheng Feng; Lin, Shu Yi; Chuang, Hui Ping; Huang, Li Chen; Chen, Ying-Ju; Tsai, Pei Joung; Liao, Hung Ting; Lin, Yu Hsuan; Chen, Chien Hsiun; Chung, Wen-Hung; Hung, Shuen Iu; Wu, Jer Yuarn; Chang, Chi-Feng; Chen, Luke; Chen, Yuan Tsong; Shen, Chen Yang; Hu, Chaur-Jong.

In: New England Journal of Medicine, Vol. 364, No. 12, 24.03.2011, p. 1126-1133.

Research output: Contribution to journalArticle

Chen, P, Lin, JJ, Lu, CS, Ong, CT, Hsieh, PF, Yang, CC, Tai, CT, Wu, SL, Lu, CH, Hsu, YC, Yu, HY, Ro, LS, Lu, CT, Chu, CC, Tsai, JJ, Su, YH, Lan, SH, Sung, SF, Lin, SY, Chuang, HP, Huang, LC, Chen, Y-J, Tsai, PJ, Liao, HT, Lin, YH, Chen, CH, Chung, W-H, Hung, SI, Wu, JY, Chang, C-F, Chen, L, Chen, YT, Shen, CY & Hu, C-J 2011, 'Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan', New England Journal of Medicine, vol. 364, no. 12, pp. 1126-1133. https://doi.org/10.1056/NEJMoa1009717
Chen, Pei ; Lin, Juei Jueng ; Lu, Chin Song ; Ong, Cheung Ter ; Hsieh, Peiyuan F. ; Yang, Chih Chao ; Tai, Chih Ta ; Wu, Shey Lin ; Lu, Cheng Hsien ; Hsu, Yung Chu ; Yu, Hsiang Yu ; Ro, Long Sun ; Lu, Chung Ta ; Chu, Chun Che ; Tsai, Jing Jane ; Su, Yu Hsiang ; Lan, Sheng Hsing ; Sung, Sheng Feng ; Lin, Shu Yi ; Chuang, Hui Ping ; Huang, Li Chen ; Chen, Ying-Ju ; Tsai, Pei Joung ; Liao, Hung Ting ; Lin, Yu Hsuan ; Chen, Chien Hsiun ; Chung, Wen-Hung ; Hung, Shuen Iu ; Wu, Jer Yuarn ; Chang, Chi-Feng ; Chen, Luke ; Chen, Yuan Tsong ; Shen, Chen Yang ; Hu, Chaur-Jong. / Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. In: New England Journal of Medicine. 2011 ; Vol. 364, No. 12. pp. 1126-1133.
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title = "Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan",
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.",
author = "Pei Chen and Lin, {Juei Jueng} and Lu, {Chin Song} and Ong, {Cheung Ter} and Hsieh, {Peiyuan F.} and Yang, {Chih Chao} and Tai, {Chih Ta} and Wu, {Shey Lin} and Lu, {Cheng Hsien} and Hsu, {Yung Chu} and Yu, {Hsiang Yu} and Ro, {Long Sun} and Lu, {Chung Ta} and Chu, {Chun Che} and Tsai, {Jing Jane} and Su, {Yu Hsiang} and Lan, {Sheng Hsing} and Sung, {Sheng Feng} and Lin, {Shu Yi} and Chuang, {Hui Ping} and Huang, {Li Chen} and Ying-Ju Chen and Tsai, {Pei Joung} and Liao, {Hung Ting} and Lin, {Yu Hsuan} and Chen, {Chien Hsiun} and Wen-Hung Chung and Hung, {Shuen Iu} and Wu, {Jer Yuarn} and Chi-Feng Chang and Luke Chen and Chen, {Yuan Tsong} and Shen, {Chen Yang} and Chaur-Jong Hu",
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T1 - Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan

AU - Chen, Pei

AU - Lin, Juei Jueng

AU - Lu, Chin Song

AU - Ong, Cheung Ter

AU - Hsieh, Peiyuan F.

AU - Yang, Chih Chao

AU - Tai, Chih Ta

AU - Wu, Shey Lin

AU - Lu, Cheng Hsien

AU - Hsu, Yung Chu

AU - Yu, Hsiang Yu

AU - Ro, Long Sun

AU - Lu, Chung Ta

AU - Chu, Chun Che

AU - Tsai, Jing Jane

AU - Su, Yu Hsiang

AU - Lan, Sheng Hsing

AU - Sung, Sheng Feng

AU - Lin, Shu Yi

AU - Chuang, Hui Ping

AU - Huang, Li Chen

AU - Chen, Ying-Ju

AU - Tsai, Pei Joung

AU - Liao, Hung Ting

AU - Lin, Yu Hsuan

AU - Chen, Chien Hsiun

AU - Chung, Wen-Hung

AU - Hung, Shuen Iu

AU - Wu, Jer Yuarn

AU - Chang, Chi-Feng

AU - Chen, Luke

AU - Chen, Yuan Tsong

AU - Shen, Chen Yang

AU - Hu, Chaur-Jong

PY - 2011/3/24

Y1 - 2011/3/24

N2 - 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.

AB - 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.

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DO - 10.1056/NEJMoa1009717

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