Reducing severe cutaneous adverse and type B adverse drug reactions using pre-stored human leukocyte antigen genotypes

Kye Hwa Lee; Dong Yoon Kang; Hyun Hwa Kim; Yi Jun Kim; Hyo Jung Kim; Ju Han Kim; Eun Young Song; James Yun; Hye-Ryun Kang

doi:10.1002/clt2.12098

Reducing severe cutaneous adverse and type B adverse drug reactions using pre-stored human leukocyte antigen genotypes

Clin Transl Allergy. 2022 Jan 14;12(1):e12098. doi: 10.1002/clt2.12098. eCollection 2022 Jan.

Authors

Kye Hwa Lee¹, Dong Yoon Kang², Hyun Hwa Kim², Yi Jun Kim³, Hyo Jung Kim⁴, Ju Han Kim⁵, Eun Young Song⁶, James Yun^{7

8}, Hye-Ryun Kang^{2

9}

Affiliations

¹ Department of Information Medicine Asan Medical Center Seoul South Korea.
² Drug Safety Center Seoul National University Hospital Seoul South Korea.
³ Institute of Convergence Medicine Ewha Womans University Mokdong Hospital Seoul South Korea.
⁴ Department of Digital Health Samsung Advanced Institute for Health Science and Technology Sungkyunkwan University Seoul South Korea.
⁵ Seoul National University Biomedical Informatics and Systems Biomedical Informatics Research Center Division of Biomedical Informatics Seoul National University College of Medicine Seoul South Korea.
⁶ Department of Molecular Medicine and Biopharmaceutical Sciences Graduate School of Convergence Science and Technology and College of Medicine Medical Research Center Seoul National University Seoul South Korea.
⁷ Department of Immunology and Rheumatology Nepean Hospital Sydney New South Wales Australia.
⁸ Faculty of Medicine and Health The University of Sydney Sydney New South Wales Australia.
⁹ Institute of Allergy and Clinical Immunology Seoul National University Medical Research Center Seoul National University College of Medicine Seoul South Korea.

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, 4092 (34.1%) had high-risk HLA alleles, 4583 (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% versus 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.

Keywords: adverse drug reaction; human leukocyte antigen; hypersensitivity; pharmacogenomics; preemptive genotyping.