title: Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians.
abstract: OBJECTIVE
  To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai).
  
  
  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.
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Chun-Bing
authors.initials: CB
authors.lastname: Chen
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authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Hsiao
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authors.forename: Tony
authors.initials: T
authors.lastname: Wu
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authors.forename: Mo-Song
authors.initials: MS
authors.lastname: Hsih
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authors.forename: Wichittra
authors.initials: W
authors.lastname: Tassaneeyakul
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authors.forename: Teekayu P
authors.initials: TP
authors.lastname: Jorns
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authors.forename: Chonlaphat
authors.initials: C
authors.lastname: Sukasem
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authors.forename: Chien-Ning
authors.initials: CN
authors.lastname: Hsu
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authors.forename: Shih-Chi
authors.initials: SC
authors.lastname: Su
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Chang
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authors.forename: Rosaline Chung-Yee
authors.initials: RC
authors.lastname: Hui
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authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Chu
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authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
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authors.forename: Ching-Ying
authors.initials: CY
authors.lastname: Wu
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authors.forename: Chao-Kai
authors.initials: CK
authors.lastname: Hsu
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authors.forename: Tsu-Man
authors.initials: TM
authors.lastname: Chiu
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authors.forename: Pei-Lun
authors.initials: PL
authors.lastname: Sun
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authors.forename: Hua-En
authors.initials: HE
authors.lastname: Lee
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authors.forename: Chin-Yi
authors.initials: CY
authors.lastname: Yang
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authors.forename: Pei-Han
authors.initials: PH
authors.lastname: Kao
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authors.forename: Chih-Hsun
authors.initials: CH
authors.lastname: Yang
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authors.forename: Hsin-Chun
authors.initials: HC
authors.lastname: Ho
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authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Lin
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authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Ming-Jing
authors.initials: MJ
authors.lastname: Chen
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authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Lu
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authors.forename: Chau Yee
authors.initials: CY
authors.lastname: Ng
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authors.forename: Kang-Ling
authors.initials: KL
authors.lastname: Kuo
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authors.forename: Chien-Yio
authors.initials: CY
authors.lastname: Lin
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authors.forename: Ching-Sheng
authors.initials: CS
authors.lastname: Yang
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authors.forename: Ding-Ping
authors.initials: DP
authors.lastname: Chen
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authors.forename: Pi-Yueh
authors.initials: PY
authors.lastname: Chang
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authors.forename: Tsu-Lan
authors.initials: TL
authors.lastname: Wu
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authors.forename: Yu-Jr
authors.initials: YJ
authors.lastname: Lin
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authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Weng
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authors.forename: Tseng-Tong
authors.initials: TT
authors.lastname: Kuo
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authors.forename: Shuen-Iu
authors.initials: SI
authors.lastname: Hung
authors.affiliation: Authors' affiliations are listed at the end of the article. chung1@cgmh.org.tw.
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Chung
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000009:adverse effects*; D044466:Asian People; D002220:Carbamazepine / Q000009:adverse effects / Q000031:analogs & derivatives*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D009313:National Health Programs / Q000706:statistics & numerical data; D000078330:Oxcarbazepine; D011446:Prospective Studies; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D013262:Stevens-Johnson Syndrome / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D013624:Taiwan; D013785:Thailand; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D002220:Carbamazepine; D000078330:Oxcarbazepine