Introduction
Adverse drug reactions (ADRs) frequently occur in patients despite
appropriate drug dosage and administration.1Idiosyncratic type B ADRs account
for approximately 20% ADRs and are mostly immune-mediated and
unpredictable.2 Occasionally, type B reactions can
have serious consequences, such as severe cutaneous adverse reactions
(SCARs) including Stevens–Johnson syndrome (SJS), toxic epidermal
necrolysis (TEN), and drug-induced hypersensitivity syndrome/drug
reaction with eosinophilia and systemic symptoms (DRESS), resulting in
death.3,4 Individual genetic variability results in
susceptibility to different ADRs; therefore, it is crucial to utilize
the genomic data of patients for drug prescription.3Currently, various genetic tests are performed in hospitals, and a vast
amount of genetic information is already pre-stored in electronic
medical records (EMRs). However, this information is rarely used for
indications outside its primary purpose.
Lack of integration between the genetic information of the patient and
the EMRs is an obstacle in patient-specific drug prescription at the
point-of-care.4 Data on major pharmacogenomic (PGx)
variants pre-stored in the EMR should be used when prescribing high-risk
drugs to patients.3,5,6 The clinical validity of the
drug–gene relationship used in this approach is mainly based on the
Clinical Pharmacogenetics Implementation Consortium
guidelines.7 Preemptive genotyping has many advantages
compared to reactive genotyping. For example, the genotype information
of patients can be used without delay in the prescription process. The
genotype information can also be used to build a system to support
physicians in making personalized prescription decisions. Furthermore,
preemptive genotyping is a cost-effective approach as many drug-related
variants can be obtained using a single panel.8 In
reality, preemptive genotyping is not widely used in clinical practice,
and PGx genes and variants found in a majority of PGx panels mainly
focus on the pharmacokinetic/pharmacodynamic genes, including cytochrome
P450 enzyme families.4 Therefore, these PGx genes are
not tested for purposes other than their use in drug prescription.
In recent decades, particular human leukocyte antigen (HLA) alleles have
been found to be strongly associated with the development of certain
drug-related SCARs.9,10 We hypothesize that use of HLA
PGx alleles can prevent SCARs. Despite the strong associations between
some HLAs and drug-related SCARs, pre-stored HLA data obtained from
transplant workup tests are not being utilized to screen individuals at
a risk of developing SCARs when high-risk drugs are prescribed. Storing
HLA data in a structured, standardized format in EMRs is challenging as
different testing methods have been used to determine HLAs over the
years. Nonetheless, if pre-existing HLA data can be successfully
retrieved and re-used based on the PGx indications, it would reduce the
costs of testing and effort required to obtain the same HLA information.
A clinical decision support system using the pre-stored genetic data can
also be utilized as a part of the point-of-care if successfully
integrated.
In a previous study, we extracted, parsed, and saved the HLA data of
transplant patients in a structured, standard format from pre-stored
unstructured HLA data.11 This study investigated the
potential clinical benefits of using the extracted HLA genotypes as a
risk prediction marker for ADR.