Carbamazepine-induced toxic effects and HLA-B*1502... [N Engl J Med. 2011] - PubMed result

N Engl J Med. 2011 Mar 24;364(12):1126-33.

Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan.
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 YJ, Tsai PJ, Liao HT, Lin YH, Chen CH, Chung WH, Hung SI, Wu JY, Chang CF, Chen L, Chen YT, Shen CY; Taiwan SJS Consortium.

Collaborators (105)Su JJ, Lee MJ, Yen DJ, Liao KK, Hong CJ, Chen C, Su MS, Chuang CP, Chen CM, Lin KP, Lin JC, Chang CA, Yuan RY, Hu CJ, Yu CM, Shen JJ, Kuo YT, Sung JY, Lai TC, Wang KC, Wang CJ, Wang HC, Yeh JH, Hsu WC, Huang KL, Chiang TR, Chung WH, Chang YJ, Hsu WC, Lin KL, Wu YL, Huang CR, Chen YC, Chien HU, Wu TC, Sung CY, Lee YY, Hsieh MJ, Huang KL, His MS, Lee TH, Lyu RK, Yeh TH, Chuang WL, Chen CC, Huang CC, Chang HS, Wu YR, Lai SC, Chu NS, Kuo HC, Huang YZ, Weng YH, Ruy SJ, Fung HC, Chen RS, Chen ST, Chang TY, Hsieh HY, Tsai YT, Cheng MY, Yip BS, Chou PC, Kuo TM, Tsai PC, Tsai CH, Liu CH, Kuo HT, Chou IC, Yang YW, Hsu YT, Tsai TC, Lin KH, Lin JC, Liu CS, Chang MY, Wu CS, Wang HP, Hung PH, Kao YH, Lee CD, Hsiao MC, Wu CY, Wong TW, Yeh PS, Lin HJ, Ke DR, Cheng TJ, Lin KC, Chang CY, Chou CH, Tseng KY, Khor GT, Hsu CY, Liou CW, Chuang YC, Chang WN, Lai SL, Lin TK, Jen HM, Liu AB, Chen WH, Lin PY, Lee MT, Wei CY.
Institute of Biomedical Sciences, Academia Sinica, Taipei, 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. (Funded by the National Science Council of Taiwan and the Taiwan Drug Relief Foundation.).

PMID: 21428768 [PubMed - in process]

Carbamazepine-induced toxic effects and HLA-B*1502... [N Engl J Med. 2011] - PubMed result

Carbamazepine-Induced Toxic Effects and HLA-B*1502 Screening in Taiwan — NEJM
Carbamazepine-Induced Toxic Effects and HLA-B*1502 Screening in Taiwan — NEJM