Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul 5:13:867490.
doi: 10.3389/fphar.2022.867490. eCollection 2022.

Implementation of HLA-B*15:02 Genotyping as Standard-of-Care for Reducing Carbamazepine/Oxcarbazepine Induced Cutaneous Adverse Drug Reactions in Thailand

Kanyawan Tiwattanon  1 , Shobana John  2   3 , Napatrupron Koomdee  2   3 , Pimonpan Jinda  2   3 , Jiratha Rachanakul  2   3 , Thawinee Jantararoungtong  2   3 , Nutthan Nuntharadthanaphong  2   3 , Chiraphat Kloypan  4   5 , Mohitosh Biswas  2   3   6 , Apisit Boongird  1   7 , Chonlaphat Sukasem  2   3   7   8   9
Affiliations

Implementation of HLA-B*15:02 Genotyping as Standard-of-Care for Reducing Carbamazepine/Oxcarbazepine Induced Cutaneous Adverse Drug Reactions in Thailand

Kanyawan Tiwattanon et al. Front Pharmacol. .

Abstract

Objective: This study aimed to investigate the clinical impact of HLA-B*15:02 pharmacogenomics (PGx) testing before carbamazepine (CBZ)/oxcarbazepine (OXC) prescriptions and to determine whether this PGx testing was associated with the reduction of CBZ/OXC-induced cutaneous adverse drug reactions (CADRs) in Thailand. Methods: This retrospective observational cohort study was conducted by obtaining relevant HLA-B*15:02 PGx-testing and clinical data from electronic medical records during 2011-2020. 384 patient data were included in this study to investigate the clinical decision on CBZ/OXC usage before and after the HLA-B*15:02 PGx testing, and 1,539 patient data were included in this study to demonstrate the incidence of CBZ/OXC-induced SCARs and SJS between HLA-B*15:02 tested and non-tested patients. To analyze and summarize the results, descriptive statistics were employed, and Fisher exact test was used to compare the clinical difference between the HLA-B*15:02 positive and negative groups and to compare the differences of SCARs incidence. Results: 384 patients were included in this study as per the inclusion criteria. Of these, 70 patients carried HLA-B*15:02, of which 63 and 65 patients were not prescribed with CBZ/OXC before and after the availability of genotyping results, respectively. In the remaining HLA-B*15:02 non-carriers, 48, and 189 patients were prescribed CBZ/OXC before and after genotyping results were available, respectively. The findings of this study showed that the incidence of SCARs of CBZ/OXC was significantly lower (p < 0.001) in the HLA-B*15:02 screening arm than in the non-screening arm. Conclusion: HLA-B pharmacogenetics testing influenced the selection of appropriate AEDs. The presence of mild rash in the HLA-B*15:02 negative group indicates that other genetic biomarker (HLA-A*31:01) and/or non-genetic variables are involved in CBZ/OXC-induced CADRs, emphasizing that CBZ/OXC prescriptions necessitate CADR monitoring. The hospital policy and clinical decision support (CDS) alert system is essential to overcome the barriers associated with the utilization of PGx guidelines into clinical practice.

Keywords: HLA-B risk alleles; carbamazepine; cutaneous adverse drug reactions; pharmacogenomics; precision medicine.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The flowchart of patients recruitment and clinical decision in HLA-B*15:02 positive (n = 70) and HLA-B*15:02 negative (n = 314) in Ramathibodi Hospital, Bangkok.
FIGURE 2
FIGURE 2
Trend of HLA-B*15:02 testing requested by out-side [n = 5,191; (A)] and in-side [n = 1,020; (B)] of Ramathibodi Hospital (19.64%) during 2011–2020.
FIGURE 3
FIGURE 3
Alternative drugs were prescribed in patients with HLA-B*15:02 positive.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Ahmed A. F., Sukasem C., Sabbah M. A., Musa N. F., Mohamed Noor D. A., Daud N. A. A. (2021). Genetic Determinants in HLA and Cytochrome P450 Genes in the Risk of Aromatic Antiepileptic-Induced Severe Cutaneous Adverse Reactions. J. Pers. Med. 11 (5), 383. 10.3390/jpm11050383 - DOI - PMC - PubMed
    1. Alvestad S., Lydersen S., Brodtkorb E. (2007). Rash from Antiepileptic Drugs: Influence by Gender, Age, and Learning Disability. Epilepsia 48 (7), 1360–1365. 10.1111/j.1528-1167.2007.01109.x - DOI - PubMed
    1. Amstutz U., Shear N. H., Rieder M. J., Hwang S., Fung V., Nakamura H., et al. (2014). Recommendations for HLA-B*15:02 and HLA-A*31:01 Genetic Testing to Reduce the Risk of Carbamazepine-Induced Hypersensitivity Reactions. Epilepsia 55 (4), 496–506. 10.1111/epi.12564 - DOI - PubMed
    1. Ang H. X., Chan S. L., Sani L. L., Quah C. B., Brunham L. R., Tan B. O. P., et al. (2017). Pharmacogenomics in Asia: A Systematic Review on Current Trends and Novel Discoveries. Pharmacogenomics 18 (9), 891–910. 10.2217/pgs-2017-0009 - DOI - PubMed
    1. Campos-Fernández Mdel M., Ponce-De-León-Rosales S., Archer-Dubon C., Orozco-Topete R. (2005). Incidence and Risk Factors for Cutaneous Adverse Drug Reactions in an Intensive Care Unit. Rev. Invest. Clin. 57 (6), 770–774. https://www.medigraphic.com/pdfs/revinvcli/nn-2005/nn056b.pdf . https://pubmed.ncbi.nlm.nih.gov/16708902/ - PubMed