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Clin Transl Allergy. 2022;12(1):e12098.

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

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제1저자 이계화 · 교신저자 강혜련

PMID 35070271 PMC8760506 DOI 10.1002/clt2.12098 IF 4.2 알레르기내과
소속 (9)
  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.

© 2022 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.

Keywords

adverse drug reactionhuman leukocyte antigenhypersensitivitypharmacogenomicspreemptive genotyping

Figures

FIGURE 1
FIGURE 1 Inclusion pipeline of the ADR‐related HLA variants and drugs. ADR, adverse drug reactions; HLA, human leukocyte antigen
FIGURE 2
FIGURE 2 Frequency of pharmacogenomics HLA allele, drug, and adverse drug reactions in patients with pre‐stored HLA data. The left side process represents patients with HLA alleles associated with ADRs (seven alleles); the middle process represents patients who were prescribed medications (seven drugs) with known HLA‐associated ADRs; and the right side process represents HLA‐related ADRs from the Drug Safety Center reports and review of the diagnoses. HLA, human leukocyte antigen; PGx, pharmacogenomics; ADRs, adverse drug reactions; SNUH, Seoul National University Hospital; SJS, Steven–Johnson syndrome; DE, drug reaction with eosinophilia and systemic symptoms
FIGURE 3
FIGURE 3 Comparison of the frequency of type B ADR and SCAR incidence for allopurinol, carbamazepine, oxcarbazepine, and vancomycin. ADR, adverse drug reactions; HLA, human leukocyte antigen; SCAR, severe cutaneous adverse reaction

그림 출처: PubMed Central 공개 논문 (PMC8760506)

Conflict of interest statement

The authors have declared no conflicts of interest.

그 밖의 정보
출판 형태
Journal Article
저널
Clinical and translational allergy · ISSN 2045-7022
전자 출판
2022-01-14
참고문헌
47편