How can the adverse skin reactions to oxcarbazepine be predicted?

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

Moon J, Kim TJ, Lim JA, et al.

Epilepsia 2016; 57:1879-1886.

ABSTRACT

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.

Similar abstract:

Chen CB, Hsiao YH, Wu T, et al; Taiwan Severe CutaneousAdverse Reaction Consortium. Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians. Neurology 2017; 88:78-86.

Both references are cited in the neurochecklist:

Antiepileptic drugs (AEDs): Oxcarbazepine

Abstract link 1

Abstract link 2

CC BY-SA 3.0, Link
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