HLA-B*40:02 and DRB1*04:03 are risk factors for oxcarbazepine-induced maculopapular eruption.

Moon, Jangsup; Kim, Tae-Joon; Lim, Jung-Ah; Sunwoo, Jun-Sang; Byun, Jung-Ick; Lee, Soon-Tae; Jung, Keun-Hwa; Park, Kyung-Il; Jung, Ki-Young; Jeon, Daejong; Yu, Kyung-Sang; Jang, In-Jin; Chu, Kon; Lee, Sang Kun

Objective Oxcarbazepine ( OXC) is a widely used antiepileptic drug for the treatment of partial seizures that was developed through structural variation of carbamazepine. Although OXC has a lower risk of cutaneous adverse drug reactions ( cADRs) than carbamazepine, cADRs ranging from maculopapular eruption ( MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis still limit the use of OXC in some patients. A few human leukocyte antigen ( HLA)-related genetic risk factors for carbamazepine-induced cADRs have been identified. However, the HLA-related genetic risk factors associated with OXC-induced cADRs are unknown. Methods A total of 40 patients who experienced OXC-induced MPE and 70 patients who were tolerant to OXC treatment were included in the study. Genomic DNA was extracted from the peripheral blood of these patients, and high-resolution HLA genotyping was performed. Results The HLA-B*40:02 and HLA- DRB1*04:03 alleles were significantly associated with OXC-induced MPE compared with the OXC-tolerant group (odds ratio [ OR] 4.33, p = 0.018 and OR 14.64, p = 0.003, respectively) and the general Korean population ( OR 4.04, p = 0.001 and OR 3.11, p = 0.019, respectively). The HLA-B*15:01 genetic frequency was significantly lower in the OXC- MPE group compared to the OXC-tolerant group ( OR 0.18, p = 0.016) and the Korean population ( OR 0.22, p = 0.030). The allele frequencies of well-known HLA-related risk factors for carbamazepine-induced c ADRs ( HLA-B*15:02, A*31:01 and B*15:11) were not different among the three groups. Significance This study is the first to demonstrate an association of HLA-B*40:02 and HLA- DRB1*04:03 with OXC hypersensitivity using a large cohort of patients with OXC-induced MPE. These findings should be confirmed in future studies in different ethnic groups.

HLA histocompatibility antigens; MACULES; DRUG side effects; SEIZURES (Medicine); CARBAMAZEPINE; STEVENS-Johnson Syndrome; NUCLEIC acid isolation methods; DISEASE risk factors; THERAPEUTICS

Epilepsia (Series 4), 2016, Vol 57, Issue 11, p1879

0013-9580

Academic Journal

10.1111/epi.13566