Adverse Drug Reactions and Pharmacogenomics: Recent Advances

Ana Alfirevic; Munir Pirmohamed

Disclosures

Personalized Medicine. 2008;5(1):11-23. 

In This Article

Abstract and Introduction

Abstract

The concept of pharmacogenomics, the study of how variation in the human genome affects response to drugs, attracts attention from clinicians and the pharmaceutical industry alike. The aim is to distinguish, using appropriate genetic tests, individuals who may be harmed by certain drugs from those who may benefit from them. Adverse drug reactions cause significant morbidity and mortality and incur a large cost to healthcare systems. Pharmacogenomics may help in the prediction and prevention of adverse reactions to drugs. While some recent studies (e.g., abacavir hypersensitivity) have shown strong associations with single genetic factors, whether these represent the exceptions rather than the rule is unclear. Further studies on adverse drug reaction pharmacogenetics are needed – these should be adequately powered and utilize the most appropriate study design that allows for an evaluation of both genetic and environmental factors. For pharmacogenetic testing to become acceptable in clinical practice, it is important that such studies are also able to provide evidence of clinical validity and clinical utility.

Introduction

The concept of pharmacogenomics, the study of how variation in the human genome affects response to drugs, is not new. The original term, pharmacogenetics, was introduced into medical literature by Vogel in 1957.[1] Although there has been a gradual increase in interest in predicting the response to drugs, this has accelerated in the last 5 years since completion of the Human Genome Project. The apparently simple idea of being able to distinguish, by appropriate genetic tests, individuals who may be harmed by certain drugs from those who may benefit from them, is very attractive to clinicians and the pharmaceutical industry alike. However, initial enthusiasm (and perhaps hype) that this will lead to tailored therapy in every discipline has been replaced with the more realistic view that pharmacogenomics will be of benefit, but will certainly not be the sole solution to the prediction and prevention of adverse drug reactions (ADRs).

ADRs can be classified into two main groups: type A and type B reactions.[2] Type A reactions are usually predictable from the known pharmacology of the drug and represent the majority (80–95%) of ADRs. Type B or idiosyncratic reactions are not predictable from the known pharmacological activity of the drug. Although type B reactions are rare, they can be serious, and cause significant morbidity and mortality, incurring a considerable cost burden to the National Health Service (NHS).[3,4] The exact mechanisms of most type B reactions have not yet been elucidated (please refer to a recent review from Uetrecht[5]). The ability to predict and prevent type B reactions through genetic testing would therefore be an important advancement from a clinical perspective in reducing morbidity and mortality, but also from a drug industry perspective in reducing the rate of attrition and drug withdrawals.

In this review, we discuss some of the new developments in the field of pharmacogenomics in relation to ADRs.

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