Insights from David Budd, CEO of genedrive, on the advances in pharmacogenetic testing technology to maintain quality of care and treatment optimisation in acute medical settings.
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Pharmacogenetic testing is increasingly recognised as a key tool in the future of personalised medicine, as it enables clinicians to identify those in whom certain drugs are ineffective, or worse, harmful. Armed with information about the genetic profiles of their patients, oncologists have, for years, been able to deliver customised treatment strategies, giving patients the correct dose of the correct medication at the correct time.
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www.edwardmoss.co.uk Edward Moss
David Budd
However, until recently, pharmacogenetics testing has relied on off-site and specialised laboratory testing which can take days or weeks to deliver results. While this timeframe is acceptable for clinicians treating long-term conditions like cancer, this is far too slow for those in need of urgent medical care. In acute medicine, clinicians do not have time to wait for test results – they need to make prescribing decisions quickly and with the information available at the time.
New bedside genetic testing to prevent permanent hearing loss in neonates with sepsis
On suspicion of neonatal sepsis, time is of the essence, and empirical antibiotics are administered as soon as possible within the ‘golden hour’ to reduce the risk of death from overwhelming response to infection. In such cases, gentamicin, an aminoglycoside antibiotic used across the UK and internationally in the emergency treatment of sepsis, is routinely prescribed. In combination with flucloxacillin or amoxicillin, it is effective against 95% of pathogens typically causing bacteraemia in newborns. It carries a lower risk of antibiotic resistance than alternatives offering cover against gram negative organisms, however, it also has the devastating consequence of inducing hearing loss in genetically susceptible babies.
Amending emergency treatment protocols to exclude gentamicin completely is not generally feasible given its track record of excellent efficacy in this setting, and the risk of antibiotic resistance of viable alternatives. However, approximately 1 in 500 babies carry a genetic variant MT-RNR1 m.1555A>G (a mitochondrial gene variant passed from mother to child) that predisposes them to hearing loss on exposure to aminoglycosides, such as gentamicin. That equates to around 180 babies in the UK suffering gentamicin-induced ototoxicity every year – 14,000 worldwide.
New point of care pharmacogenetics technology now being rolled out across Neonatal Intensive Care Units (NICUs) is changing this and rendering this tragic side effect entirely avoidable. Using this bedside test, newborn infants admitted to the NICU can be screened for the MT-RNR1 m.1555A>G variant via a simple non-invasive swab test that delivers results in just 26 minutes. Neonates carrying the variant can then be prescribed an alternative antibiotic, preserving hearing that would otherwise be lost on exposure to just a single dose of gentamicin, and ensuring that resistance-inducing antibiotics are used sparingly in only those in whom gentamicin is contraindicated.
Personalising treatment for patients in A&E
The potential clinical usage of such point of care testing is boundless and will enable clinicians to create personalised treatment plans, ultimately giving patients the best possible chance for a positive outcome. When patients are admitted to hospital after suffering a heart attack or stroke, clopidogrel, a well-established anti-platelet medication that reduces the risk of thrombosis, is routinely prescribed. However, it relies on the patient’s CYP2C19 liver enzyme for activation before it can exert its intended effect. Unfortunately, a large minority (10-20%) of people are unable to enzymatically convert clopidogrel into its active form, rendering it entirely useless.
Identifying these patients on admission to hospital using a point of care test will change their treatment outcome. Patients who are resistant to Clopidogrel can be given an appropriate alternative, such as Ticagrelor which is not the favoured drug due to additional potential side effects, but lifesaving when given to the right people. Up to 100,000 strokes each year could be avoided by CYP2C19 genotyping.
Codeine phosphate is another drug commonly prescribed for pain relief in emergency situations. But, like Clopidogrel, it relies on a liver enzyme – CYP2D6 – for conversion to active morphine. Genetic variants of this enzyme interfere with conversion, eliminating the pain-relieving properties of the drug. The result is an inappropriate escalation up the pain ladder, leading to the prescription of increasingly strong painkillers (and exposure to the myriad side effects). Alternatively, super-metabolisers are at risk of toxicity if conversion is too rapid resulting in elevated serum levels of morphine. Pharmacogenetics testing removes all uncertainty relating to patient response, helping thousands of people avoid unnecessary pain.
Pharmacogenetics and the future of personalised medicine
Customising treatment to individual patients is key to facilitating the best possible outcome following an illness; the patient receives the right medication, at the right time, at the right dose. Rapid genetic testing is now proven in emergency medical settings and can be accomplished at a patient’s bedside in less than half an hour. This technology could be used in numerous healthcare settings to ensure patients receive the right treatment based on their genetic profile, eliminating unnecessary and harmful adverse drug reactions – thought to affect between 10 and 20% of hospital in-patients.
The Royal College of Physicians and the British Pharmacological Society have called for the swift introduction of pharmacogenetic testing across the NHS in a drive to optimise treatment, and ensure clinicians have information about the genetic profile of their patients at their fingertips. The benefits to patients are obvious, but personalisation will also provide significant cost savings to healthcare providers. The requirement for expensive lab testing will be reduced, and clinicians can prescribe the most cost effective drug with confidence that it is right for that person, reducing the financial burden of chronic health conditions caused by adverse drug reactions.