Open AccessReducing severe cutaneous adverse and type B adverse drug reactions using pre‐stored human leukocyte antigen genotypes
Author(s) -
Lee Kye Hwa,
Kang Dong Yoon,
Kim Hyun Hwa,
Kim Yi Jun,
Kim Hyo Jung,
Kim Ju Han,
Song Eun Young,
Yun James,
Kang HyeRyun
Publication year - 2022
Publication title -
clinical and translational allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.979
H-Index - 37
ISSN - 2045-7022
DOI - 10.1002/clt2.12098
Subject(s) - medicine , abacavir , allopurinol , human leukocyte antigen , toxic epidermal necrolysis , odds ratio , incidence (geometry) , adverse drug reaction , adverse effect , carbamazepine , oxcarbazepine , pharmacogenomics , gastroenterology , immunology , drug , pharmacology , dermatology , antigen , epilepsy , hepatitis b virus , virus , physics , psychiatry , lamivudine , optics
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.