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: Chun-Bing Chen, Yi-Hsin Hsiao, Tony Wu, Mo-Song Hsih, Wichittra Tassaneeyakul, Teekayu P Jorns, Chonlaphat Sukasem, Chien-Ning Hsu, Shih-Chi Su, Wan-Chun Chang, Rosaline Chung-Yee Hui, Chia-Yu Chu, Yi-Ju Chen, Ching-Ying Wu, Chao-Kai Hsu, Tsu-Man Chiu, Pei-Lun Sun, Hua-En Lee, Chin-Yi Yang, Pei-Han Kao, Chih-Hsun Yang, Hsin-Chun Ho, Jing-Yi Lin, Ya-Ching Chang, Ming-Jing Chen, Chun-Wei Lu, Chau Yee Ng, Kang-Ling Kuo, Chien-Yio Lin, Ching-Sheng Yang, Ding-Ping Chen, Pi-Yueh Chang, Tsu-Lan Wu, Yu-Jr Lin, Yi-Ching Weng, Tseng-Tong Kuo, Shuen-Iu Hung, Wen-Hung Chung, Taiwan Severe Cutaneous Adverse Reaction Consortium
• Journal: Neurology (Neurology) Vol. 88 Issue 1 Pg. 78-86 (Jan 03 2017) ISSN: 1526-632X [Electronic] United States
• PMID: 27913699 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © 2016 American Academy of Neurology.

Chemical References

• Anticonvulsants
• HLA-A Antigens
• HLA-B Antigens
• Carbamazepine
• Oxcarbazepine

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anticonvulsants (adverse effects)
• Asian People
• Carbamazepine (adverse effects, analogs & derivatives)
• Child
• Child, Preschool
• Epilepsy (drug therapy)
• Female
• Gene Frequency
• Genetic Predisposition to Disease (genetics)
• Genotype
• HLA-A Antigens (genetics)
• HLA-B Antigens (genetics)
• Humans
• Incidence
• Male
• Meta-Analysis as Topic
• Middle Aged
• National Health Programs (statistics & numerical data)
• Oxcarbazepine
• Prospective Studies
• Retrospective Studies
• Statistics, Nonparametric
• Stevens-Johnson Syndrome (epidemiology, etiology, genetics)
• Taiwan
• Thailand
• Young Adult