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Genomics in action

Point-of-care pharmacogenomic testing

Traditional pharmacogenomic testing has a turnaround time of several days, which makes it unsuitable for clinical scenarios in which a pharmacogenomic result could inform prescribing in an acute setting. Point-of-care tests offer a possible solution to this issue.

Introduction

In recent years, several methodological approaches have been developed to test for genetic variants in the near-patient setting. These technologies have expanded further following the Covid-19 outbreak, which necessitated innovation in many areas, including the development of molecular point-of-care tests (POCTs) to facilitate rapid diagnosis.

Academia and industry collaborated to produce new diagnostics at an unparalleled pace, and the experience has created a landscape in which near-patient diagnostics is becoming increasingly viable as an approach to rapidly test for human genetic variation. Pharmacogenomics is one area of genomics in which rapid genotyping could influence clinical decisions and outcomes.

Existing point-of-care systems

One of the first examples of a clinically utilised genomic POCT was Cepheid’s GeneXpert assay, designed to identify the BCR-ABL gene fusion. This approach combined reverse transcription-PCR and real-time fluorescence detection, which allowed for quantitation of the fusion mRNA as part of a lyophilised (freeze-dried) system. Other companies have since developed rapid assays, utilising a range of technological approaches, to genotype pharmacogenomic variation related to several commonly prescribed medicines, including:

Clinical scenarios

A case can be made for the development of a pharmacogenomic POCT in the following scenarios:

  • where there is clinical need to initiate drug treatment promptly (that is, treatment cannot wait for standard turnaround times) because there is a risk of a severe adverse drug reaction associated with a genetic variant, which may occur after only one or a few doses (for example, aminoglycoside antibiotics and MT-RNR1);
  • where the influence of genetic variation is most important in the initial period after starting a new drug (for example, warfarin and CYP2C9 and/orVKORC1);
  • where POCT enables genetics-informed prescribing to fit more easily into existing patient pathways (for example, POC CYP2C19 testing after an acute coronary syndrome enables the use of genetic information to guide clopidogrel prescribing by cardiologists or internists prior to discharge); and
  • in low-resource settings in which there is limited access to laboratory infrastructure.

Pharmacogenomic point-of-care tests in clinical practice

The concept of a genomic POCT is relatively new and, until recently, genotyping technology has not been sufficiently advanced or validated to deliver the required genotype results in a clinically relevant timeframe or to a clinically accredited standard. As such, there are currently no pharmacogenomic POCTs used routinely in clinical practice, either in the UK or globally. However, in the research setting a number of POCTs have been trialled in the following clinical scenarios.

  • Optimising anticoagulant therapy: A POCT was developed to genotype variants within CYP2C9 and VKORC1, known to be relevant to warfarin dosing. This was then evaluated as part of a multi-centre randomised controlled trial involving patients with atrial fibrillation and venous thromboembolism. The findings were reported in the New England Journal of Medicine in 2013.
  • Optimising antiplatelet therapy: A POCT was developed to genotype the major clinically actionable variants within CYP2C19, known to be related to the metabolism of clopidogrel. This technology was then used as part of a randomised controlled trial to test genotype-guided prescribing in patients undergoing primary percutaneous coronary intervention.
  • Avoiding aminoglycoside-induced hearing loss: A POCT was developed to genotype the m.1555A>G variant in MT-RNR1, known to be associated with aminoglycoside-induced ototoxicity. The system was integrated into routine clinical practice at two UK-based neonatal intensive care units and implemented to support genotype-guided prescribing of antibiotics. Those babies who carried the m.1555A>G variant were prescribed an alternative antibiotic, thereby avoiding the risk of aminoglycoside-induced ototoxicity.

Summary

POCT strategies have the potential to overcome issues of lengthy turnaround times which, in certain clinical settings, may prevent the implementation of pharmacogenomics. New diagnostic technologies are likely to reduce the cost and speed of POCT over the next decade.

Resources

For clinicians

References:

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  • Last reviewed: 04/08/2023
  • Next review due: 04/08/2025
  • Authors: Dr John McDermott
  • Reviewers: Charlotte Barker