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.
Keywords: Adverse drug reaction, Human leukocyte antigen,
Hypersensitivity, Pharmacogenomics, Preemptive genotyping