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Reducing severe cutaneous adverse and type B adverse drug reactions using pre-stored HLA genotypes
  • +6
  • Kye Hwa Lee,
  • Dong Yoon Kang,
  • Hyun Hwa Kim,
  • Yi-Jun Kim,
  • Hyo Jung Kim,
  • Ju-Han Kim,
  • Song Eun Young,
  • James Yun,
  • Hye-Ryun Kang
Kye Hwa Lee
Asan Medical Center

Corresponding Author:geffa79@gmail.com

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Dong Yoon Kang
Seoul National University Hospital
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Hyun Hwa Kim
Seoul National University Hospital
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Yi-Jun Kim
Ewha Womans University Mokdong Hospital
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Hyo Jung Kim
Sung Kyun Kwan University
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Ju-Han Kim
Seoul National University College of Medicine
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Song Eun Young
Seoul National University College of Medicine
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James Yun
The University of Sydney
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Hye-Ryun Kang
Seoul National University College of Medicine
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Abstract

Background: Several type B adverse drug reactions (ADRs), especially severe cutaneous adverse reactions (SCARs), are associated with particular human leukocyte antigen (HLA) genotypes. However, pre-stored HLA information obtained from other clinical workups has not been used to prevent ADRs. We aimed to simulate the preemptive use of pre-stored HLA information in electronic medical records to evaluate whether this information can prevent ADRs. Methods: We analyzed the incidence and the risk of ADRs for selected HLA alleles (HLA-B*57:01, HLA-B*58:01, HLA-A*31:01, HLA-B*15:02, HLA-B*15:11, HLA-B*13:01, HLA-B*59:01, and HLA-A*32:01) and seven drugs (abacavir, allopurinol, carbamazepine, oxcarbazepine, dapsone, methazolamide, and vancomycin) using pre-stored HLA information of transplant patients based on the Pharmacogenomics Knowledge Base guidelines and experts’ consensus. Results: Among 11,988 HLA-tested transplant patients, 4,092 (34.1%) had high-risk HLA alleles, 4,583 (38.2%) were prescribed risk drugs, and 580 (4.8%) experienced type B ADRs. Patients with HLA-B*58:01 had a significantly higher incidence of type B ADR and SCARs associated with allopurinol use than that of patients without HLA-B*58:01 (17.2% vs. 11.9%, odds ratio (OR) 1.53 [95% confidence interval (CI) 1.09–2.13], P = 0.001, 2.3% vs. 0.3%, OR 7.13 [95% CI 2.19–22.69], P < 0.001). Higher risks of type B ADR and SCARs were observed in patients taking carbamazepine or oxcarbazepine if they had one of HLA-A*31:01, HLA-B*15:02, or HLA-B*15:11 alleles. Vancomycin and dapsone use in HLA-A*32:01 and HLA-B*13:01 carriers, respectively, showed trends toward increased risk of type B ADRs. Conclusion: Utilization of pre-stored HLA data can prevent type B ADRs including SCARs by screening high-risk patients.
Jan 2022Published in Clinical and Translational Allergy volume 12 issue 1. https://doi.org/10.1002/clt2.12098