Risk and association of <i>HLA</i> with oxcarbazepine-induced cutaneous adverse reactions in Asians

Abstract

<h3>Objective:</h3> 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). <h3>Methods:</h3> 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 <i>HLA-B*15:02</i> and <i>HLA-A*31:01</i> 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. <h3>Results:</h3> 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 <i>HLA-B*15:02</i> and OXC-SJS (<i>p</i> = 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 <i>HLA-B*15:02</i> for OXC-SJS/TEN were 0.73% and 99.97%, respectively. <i>HLA-A*31:01</i> was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (<i>p</i> = 0.003; relative risk 0.212; 95% CI 0.077–0.584). <h3>Conclusions:</h3> Our findings suggest that <i>HLA-B*15:02</i> 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 <i>HLA-B*15:02</i> screening should be evaluated further.