Pharmacogenetic tests yield bonus benefit: better drug adherence

Elie Dolgin

Journal name:: Nature Medicine
Volume:: 19,
Pages:: 1354–1355
Year published:: (2013)
DOI:: doi:10.1038/nm1113-1354

Published online: 07 November 2013

The KIF6 Genotype Test is a controversial product. The $100 test from California's Berkeley HeartLab arrived on the market in 2008 and determines whether people harbor a common DNA variant in the kinesin-like protein 6 (KIF6) gene—a variant some studies initially linked with both an elevated risk of heart disease and a better-than-average response to cholesterol-lowering statin therapy. However, those associations have been challenged in recent years, and now few cardiologists recommend taking this test of uncertain clinical utility. Furthermore, few US insurance companies will pay for KIF6 testing.
But there is an unexpected twist: even if KIF6 status has no bearing on clinical outcomes, just the act of testing for mutations in the gene and telling people that information seems to have an unintended benefit. According to a study published online in late August in The Pharmacogenomics Journal (doi:10.1038/tpj.2013.27, 2013), providing KIF6 test results to patients on statin therapy, regardless of what the test says, significantly reduces the number of days in which they omit to take their drugs and increases the average length of time over which they continue to take their medications.

3D4Medical / Science Source

Easier pill to swallow: Pharmacogenetics prompts people to take their medicines.

“This was really a study in which we broke new ground by looking at a totally different use of genetic information than for making a clinical decision,” says study author Felix Frueh, executive partner of the Maryland consulting firm Opus Three and former president of the research arm of the healthcare company Medco (now a subsidiary of Express Scripts, a pharmacy benefit management company headquartered in St. Louis). “It illustrates the impact that genetics can have in a more psychological way on patient behavior.”
Drug adherence is loosely defined as taking your medications as directed at least 80% of the time. That may sound like a relatively low bar for success, and yet up to half of all prescription drug takers in the US do not meet this threshold—a problem that is estimated to cost the healthcare system more than $177 billion per year. Comprehensive intervention programs, including those that involve monitoring and feedback, can improve medication-taking behavior, but these tend to be expensive and time consuming, with effects that are not always consistent. Pharmacogenetic testing provides an alternative route to promoting patient buy-in.

Sticking to it

In their recently published study, Frueh and his Medco colleagues offered KIF6 genotyping to approximately 1,500 people who were new to statin therapy, around half of whom consented to undergo testing. After six months, they found that about 63% of those participants who received the test could be classified as adherent. In contrast, only 45% of matched controls not offered KIF6 testing were adherent, compared to about 51% of individuals who declined genotyping but were reminded about routine adherence monitoring.
Importantly, the bump in adherence occurred in test recipients irrespective of their actual KIF6 carrier status, according to a preliminary analysis conducted by study author Scott Charland, who now serves as a health outcomes liaison with Sanofi in Winter Park, Colorado. (Charland and his colleagues are now preparing an additional manuscript comparing people with and without the KIF6 mutation.)
“The notion that genetic testing, regardless of the result, improves adherence and other outcomes is an interesting one that's worth further exploration,” says Kiran Musunuru, a physician-scientist at Harvard University in Cambridge, Massachusetts, who studies the genetics of cardiovascular disease but was not involved in the study. “Perhaps the act of receiving genetic information simply heightens one's vigilance with respect to medical issues.”
Susanne Haga, a health policy researcher at the Duke University Institute for Genome Sciences and Policy in Durham, North Carolina, who coauthored a recent perspective article on the potential impacts of pharmacogenetic testing on medication-taking behavior, agrees. In her article, published in the December issue of The Pharmacogenomics Journal (13, 481–483, 2013), Haga notes that an uptick in adherence, although not usually the primary goal of pharmacogenetic testing, can be an unintended consequence simply because the inherently personal nature of learning how likely one is to respond favorably to a given drug can increase perceived need, decrease anxiety levels and provide a greater sense of shared decision-making—all of which can entice people to regularly take their meds.
“You can improve patient confidence that a drug will be effective and do what it's supposed to do,” Haga says. But, she cautions, “a lot of this pivots on the patient's understanding of what this information means and how it's communicated.”

Statin switcheroo

Haga recently completed a pilot study testing whether using pharmacogenetics can improve pill-taking behavior in 58 people with poor statin adherence. Together with Duke cardiologist Deepak Voora, Haga genotyped study participants for a particular variant in the SLCO1B1 gene that has been associated with a painful muscle disease known as statin-induced myopathy. This side effect is most pronounced in people taking simvastatin or atorvastatin, and it can usually be avoided by switching to alternatives such as pravastatin or rosuvastatin.
In their pilot study, Haga, Voora and their team used the results of the pharmacogenetic test to advise participants whether swapping statins could help minimize their risk of myopathy. This intervention, they found, improved participants' perceptions of statins and promoted higher drug adherence compared to controls. The Duke researchers presented their findings on 23 October at the American Society for Human Genetics Annual Meeting in Boston. In collaboration with medical staff from the US Air Force, they are now running a larger confirmatory trial involving 375 statin takers who live on the Travis Air Force Base in Northern California.

US Air Force

A tour de force: This Air Force base clinic is using genetic testing to improve statin adherence.

Meanwhile, some pharmacogenetic studies are now starting to look at the issue of adherence outside the realm of statin usage. For example, Ohio-based Assurex Health, in collaboration with Medco/Express Scripts, recently completed a one-year trial evaluating the potential of pharmacogenetic testing to change medication-taking behavior among people with mental illness—a group with some of the lowest rates of drug adherence. In that study, close to 2,200 people who had recently switched psychiatric drugs received a pharmacogenetic test called GeneSight, which evaluated five genes involved in the metabolism of and response to antidepressant and antipsychotic medications.
Assurex's senior vice president of medical affairs and clinical development, Bryan Dechairo, has done a first pass at crunching the numbers. He says that of 1,260 test recipients who changed their prescriptions again, presumably after the GeneSight test results suggested that an alternate medication might be more suitable, only 33% had stopped taking those drugs after six months, compared with 41% of matched controls who swapped drugs through an unguided process of trial and error. And of those who did drop their meds, this generally happened later among test recipients—after 58 days, on average, as opposed to 38 days for matched controls.
Add on top of that the anticipated clinical benefits of the GeneSight test, and James Burns, chief executive of Assurex, sees these elements coming together to create a snowball effect toward better health outcomes and reduced healthcare costs. “If adherence does increase,” he says, “then all the other pieces should follow.”
“This is one of those interesting parts of personalized information,” notes Dan Roden, a clinical pharmacologist and cardiologist at the Vanderbilt University School of Medicine in Nashville, Tennessee, who has pioneered the use of pharmacogenetics in routine care of cardiovascular disease. “It's not just about genomics, that's for sure.”