HLA‐B*40:02 and DRB1*04:03 are risk factors for oxcarbazepine‐induced maculopapular eruption. (26th September 2016)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Epilepsia. Volume 57:issue 11(2016)
• Page Start: 1879
• Page End: 1886
• Publication Date: 2016-09-26
• Subjects: Oxcarbazepine -- Maculopapular eruption -- Human leukocyte antigen; Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.13566
• Languages: English
• ISSNs: 0013-9580

Abstract

Summary: 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 cADRs (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.