Abstract
Human Leukocyte Antigen (HLA) variants can be a risk factor for developing potentially fatal drug hypersensitivity reactions. Our aim was to estimate the potential impact of genotyping for the HLA risk alleles incorporated in the Dutch Pharmacogenetics Working Group (DPWG) guidelines in The Netherlands. We estimated the number of hypersensitivity reactions and associated deaths that can be avoided annually by genotyping for these HLA risk alleles. Additionally, the cost-effectiveness was estimated. Nationwide implementation of genotyping HLA risk alleles before initiating drugs with an actionable drug–gene interaction can potentially save the life of seven allopurinol initiators and two flucloxacillin initiators each year in The Netherlands. Besides these deaths, 28 cases of abacavir hypersensitivity, 24 cases of allopurinol induced SCARs, 6 cases of carbamazepine induced DRESS and 22 cases of flucloxacillin induced DILI can be prevented. Genotyping HLA-B*5701 in abacavir initiators has a number needed to genotype of 31 to prevent one case of abacavir hypersensitivity and is cost-saving. Genotyping HLA-B*5801 in allopurinol initiators has a number needed to genotype of 1149 to prevent one case of SCAR but is still cost-effective. Genotyping before initiating antiepileptic drugs or flucloxacillin is not cost-effective. Our results confirm the need for mandatory testing of HLA-B*5701 in abacavir initiators, as indicated in the drug label, and show genotyping of HLA-B*5801 in allopurinol initiators should be considered.
Highlights
Accepted: 17 December 2021Adverse drug reactions (ADRs) are a major cause of morbidity and mortality in modern healthcare
Bouvy et al performed a review of all epidemiological studies quantifying Accepted: December 2021Adverse drug reactions (ADRs) in a European setting and found a median percentage of ADR related hospital admissions of 3.5% of all admissions and a fatality rate of approximately 0.15% indicating that ADRs represent a significant burden on European healthcare [2]
An overview of first dispensations obtained from the Dutch Foundation for Pharmaceutical Statistics or Stichting Farmaceutische Kerngetallen (SFK) of abacavir, allopurinol, carbamazepine, flucloxacillin, lamotrigine, oxcarbazepine and phenytoin for the period
Summary
Adverse drug reactions (ADRs) are a major cause of morbidity and mortality in modern healthcare. An adverse drug reaction (ADR) is defined by the World Health. Incidence numbers of idiosyncratic ADRs are scarcely available within Caucasian cohorts, but according to Asian studies the incidence of drug hypersensitivity of hospitalized patients is estimated to be 1.8–4.2 per 1000 hospital admissions [3,4]. They are rare but, due to them being unpredictable and often severe with high mortality rates, genetic biomarkers to identify patients at higher
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