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Gene-directed prescribing coming to general practice

It’s been around for some time now. The idea of checking a person’s genes to guide appropriate prescribing is not new. It is pretty much standard practice when treating many if not most cancers.

But pharmacogenomics in general practice? Looking at an individual’s genetic variants to work out the best treatment for their depression, high cholesterol or gout? Yes – it’s coming.

As authors of a recently published review in the Australian Journal of General Practice say, all practising clinicians will have had the experience of patients responding differently to medications despite every indication the medication should be effective, based on all the evidence from randomised controlled trials.

It is known that certain genes that regulate the absorption, distribution, metabolism and excretion (ADME) of medications are commonly responsible for this difference in response, as these genes can vary between individuals. Researchers have also identified another group of genes that can influence medication responses directly, which, while less common can have important implications for prescribing.

“For example, carbamazepine should not be prescribed to patients with certain human leucocyte antigen (HLA) genotypes because of an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis,” the Australian review authors said.

Overall, there have been at least 15 genes identified for which testing can be useful and clinically beneficial in guiding prescribing of 30 different medications.

How important will this be in general practice?

According to this review at least, very. Firstly the likelihood of having a genetic variation that will influence how a person responds to a common medication is incredibly high.

“A recent study of 5400 Australians who underwent testing of just four ADME genes showed that 96% had at least one clinically actionable pharmacogenomic variant,” the review authors said.

And then the likelihood that a person will be prescribed one of the drugs that we can now predict the response based on genetic testing is also incredibly high. On analysis of PBS data from 2017, the researchers determined that in that year approximately 1.7 million Australians had filled a prescription for at least one the drugs that has the highest level of evidence of clinically relevant gene-medication association.

In their review the authors present a number of case studies which demonstrate the usefulness of genetic testing in clinical practice. These include a patient with anxiety and depression who fails to respond to standard treatment leading to a significant deterioration of her condition. Genetic testing of CYP enzymes found the patient had a genetic variation that meant they rapidly metabolised certain antidepressants, but could be prescribed an alternative medication that wasn’t as dependent on the affected enzyme.

Another example involved an older Han Chinese man who needed to be prescribed allopurinol for gout. Because this particular ethnicity has a 20% chance of carrying a gene that puts them at risk of developing severe cutaneous adverse reaction to allopurinol, gene testing was done to help ensure this risk was minimised.

Similarly, a genetic variation that gives a higher than normal risk of muscle toxicity when taking simvastatin or atorvastatin can be tested for prior to patients being prescribed these medications, and a safer alternative statin offered.

Fundamentally this type of testing will lead to more effective, safer prescribing. The problem is of course, pharmacogenomic testing does not attract a Medicare rebate in Australia and the cost is prohibitive for most patients, even though, according to the review authors the costs are decreasing all the time. A panel of common CYP enzymes now costs between $150 and $200.

But the authors suggest this situation will have to change. Even on the basis of economics alone, the government needs to consider allowing rebates for at least some pharmacogenomic tests.

“A report in 2008 estimated that the widespread implementation of such testing in Australia could yield savings in excess of $1 billion annually by the avoidance of adverse medication reactions alone,” they said.

And imagine how much time, money and angst could be saved if doctors could ensure the first antidepressant a patient is prescribed had a high likelihood of having an effect, rather than the current trial and error approach.

However while we wait for better reimbursement for this testing, the authors suggest the doctors consider using the tests where appropriate in patients who are prepared to pay.

“Responsible doctors can use the tests and evidence that are already available to improve prescribing decisions for their patients,” they conclude.

Reference

Polasek TM, Mina K, Suthers G. Pharmacogenomics in general practice: The time has come. AJGP. 2019 March; 48(3): 100-5. Available from: https://www1.racgp.org.au/ajgp/2019/march/pharmacogenomics-in-general-practice