The HLA-B*15:02 polymorphism and Tegretol ® -induced serious cutaneous reactions in epilepsy: An updated systematic review and meta-analysis.

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  • Additional Information
    • Source:
      Publisher: Masson Country of Publication: France NLM ID: 2984779R Publication Model: Print Cited Medium: Internet ISSN: 0035-3787 (Print) Linking ISSN: 00353787 NLM ISO Abbreviation: Rev Neurol (Paris) Subsets: MEDLINE
    • Publication Information:
      Publication: Paris : Masson
      Original Publication: Paris.
    • Subject Terms:
      Anticonvulsants/*adverse effects ; Carbamazepine/*adverse effects ; Drug Eruptions/*genetics ; Epilepsy/*complications ; Epilepsy/*genetics ; HLA-B Antigens/*genetics; Anticonvulsants/therapeutic use ; Carbamazepine/therapeutic use ; Epilepsy/drug therapy ; Humans ; Polymorphism, Genetic
    • Abstract:
      Tegretol ® [carbamazepine (CBZ)], an aromatic drug approved for epilepsy treatment, can induce adverse drug reactions (ADRs) after its administration. Several genetic studies of epilepsy have shown that genetic polymorphisms increase the risk of ADRs, and some interactions between CBZ and other treatments can also induce adverse effects. Thus, to avoid such interactions and to provide an overview of the genetic profiles involved in ADRs with CBZ, for the first time, a systematic review and meta-analysis focusing on epilepsy was performed, using Cochrane Library, Embase and PubMed databases to find studies published between January 1980 and October 2016. Of the eligible studies, those selected were related to the impact of genetic polymorphisms on ADRs in patients receiving antiepileptic treatment. The results of these selected studies are expressed as pooled odds ratios (ORs) with 95% confidence intervals (CIs), based on data from individual patients. Out of 807 articles, nine were included in the present meta-analysis to assess the association between human leukocyte antigen (HLA)-B*15:02 polymorphisms and CBZ-induced serious cutaneous reactions (SCRs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), in epilepsy. It was found that HLA-B*15:02 polymorphisms were significantly associated with CBZ SCR risk (OR: 27.325, 95% CI: 9.933-51.166), while subgroup analyses by ethnicity showed that the association was significant in Han Chinese (OR: 42.059, 95% CI: 9.587-184.514). The HLA-B*15:02 polymorphism was also strongly associated with the CBZ-SJS subgroup (OR: 152.089, 95% CI: 34.737-665.901) and significantly associated with the CBZ-SJS/TEN subgroup (OR: 13.993, 95% CI: 7.291-26.856). Also, the allele was overrepresented in the Han Chinese population (OR: 17.886, 95% CI: 8.411-38.034) within the CBZ-SJS/TEN subgroup. Although the number of studies available in other Asian ethnicities was insufficient for determining publication bias, it nevertheless showed a relationship between the HLA-B*15:02 polymorphism and SCRs. In addition, despite the small number of included studies, the results reveal strong evidence that the HLA-B*15:02 polymorphism can induce SCRs among Asian CBZ users. These findings should prompt physicians to individualize CBZ therapy for patients with epilepsy.
      (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
    • Contributed Indexing:
      Keywords: Carbamazepine; Epilepsy; HLA-B*15:02 polymorphism; Meta-analysis; Serious cutaneous reactions
    • Accession Number:
      0 (Anticonvulsants)
      0 (HLA-B Antigens)
      33CM23913M (Carbamazepine)
    • Publication Date:
      Date Created: 20180425 Date Completed: 20181102 Latest Revision: 20181202
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.neurol.2017.11.006
    • Accession Number:
      29685430