The use of pharmacogenetics to prevent hypersensitivity reactions and side effects

Abstract

Pharmacogenetics (PGx) is the study of how variability in genes affects a person’s drug response. By using PGx, adverse drug reactions (ADRs) can be prevented, which is important as ADRs are a major cause of hospitalization and mortality. The benefits of PGx before initiating drug treatment are well documented for some genes. However, the clinical utility of implementation of a pre-emptive PGx panel test remained unclear. Part I shows the results of the Pharmacogenomic Testing for Preventing Adverse Drug Reactions (PREPARE) study where a pre-emptive PGx panel test was successfully implemented and lead to a 30% lower risk of ADRs. The PREPARE test focused mainly on side effects whereas in part II the focus was on HLA-associated hypersensitivity reactions. Here we studied the diagnostic test criteria of the HLA risk allele genes for the prediction of specific hypersensitivity reactions. Part II also includes an impact analysis including a cost-effectiveness study on the implementation of HLA genes, a feasibility study of repurposing HLA genotypes to prevent drug hypersensitivity reactions, a Dutch Pharmacogenetics Working Group guideline and two studies on potential risk factors of hypersensitivity reactions, namely atopic disease and carriers of many HLA risk alleles.