Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians.
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Chen Chun-Bing, Hsiao Yi-Hsin, Wu Tony, Hsih Mo-Song, Tassaneeyakul Wichittra, Jorns Teekayu P, Sukasem Chonlaphat, Hsu Chien-Ning, Su Shih-Chi, Chang Wan-Chun, Hui Rosaline Chung-Yee, Chu Chia-Yu, Chen Yi-Ju, Wu Ching-Ying, Hsu Chao-Kai, Chiu Tsu-Man, Sun Pei-Lun, Lee Hua-En, Yang Chin-Yi, Kao Pei-Han, Yang Chih-Hsun, Ho Hsin-Chun, Lin Jing-Yi, Chang Ya-Ching, Chen Ming-Jing, Lu Chun-Wei, Ng Chau Yee, Kuo Kang-Ling, Lin Chien-Yio, Yang Ching-Sheng, Chen Ding-Ping, Chang Pi-Yueh, Wu Tsu-Lan, Lin Yu-Jr, Weng Yi-Ching, Kuo Tseng-Tong, Hung Shuen-Iu, Chung Wen-Hung, Taiwan Severe Cutaneous Adverse Reaction Consortium
Аннотация
METHODS: We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate of HLA-B*15:02 and HLA-A*31:01 of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)-induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database.
RESULTS: We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6 drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association between HLA-B*15:02 and OXC-SJS (p = 1.87 × 10-10; odds ratio 27.90; 95% confidence interval [CI] 7.84-99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values of HLA-B*15:02 for OXC-SJS/TEN were 0.73% and 99.97%, respectively. HLA-A*31:01 was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p = 0.003; relative risk 0.212; 95% CI 0.077-0.584).
CONCLUSIONS: Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further.