Written by Julie Bick, Ph.D.
As the global population ages, the number of geriatric patients—those aged 65 and older—is rapidly increasing in almost every country. This change in population demographic will result in significant challenges to healthcare systems worldwide, particularly regarding the management of chronic diseases and the safe use of medications. One tool helping address that is now gaining momentum is ‘pharmacogenomic (PGx) testing’. This field, which combines pharmacology and genomics to deliver personalized medicine by tailoring drug therapies based on an individual's genetic makeup. For geriatric patients, PGx testing is proving to be particularly transformative, and is demonstrated to improve patient quality of life through more effective and safer medication regimens.
PGx is the study of how genes affect a person's response to small molecule-based drugs. This is not a new field, but there is now a growing interest to understand the genetic factors that influence the body's response to medications, including how drugs are absorbed-, metabolized-, secreted-, the degree of their therapeutic effect, and the risk of potential side effects for any individual. Key genes involved in drug metabolism, such as those encoding cytochrome P450 enzymes, vary between individuals. These variations can lead to differences in how quickly or slowly drugs are processed in the body, affecting their efficacy and the risk of side effects. PGx testing identifies these genetic variants, enabling healthcare providers to tailor drug therapies to the individual’s genetic profile, helping to optimize medication doses and reduce side effects, or identify drugs that may have the potential of serious adverse drug reactions (ADRs) for that patient and should be avoided all together.
Geriatric patients often have multiple chronic conditions, requiring complex and frequently very expensive medication regimens. The geriatric population is also more susceptible to ADRs due to physiological changes associated with aging, such as decreased renal and hepatic function, and altered drug absorption and distribution (Brockmoller et. al. 2017) that collectively change their pharmacokinetic and pharmacodynamic profiles (Ruiter et. al. 2012). All of these factors are significant when it comes to medication management, for example, reduced renal function can impair the excretion of drugs and their metabolites, leading to drug accumulation and potential toxicity. Similarly, changes in body composition as we age, such as increased fat and decreased muscle mass, can alter the distribution of lipophilic and hydrophilic drugs, respectively (Routledge et. al. 2004) resulting in ineffective mediations or toxicity. Until recently, these factors were rarely considered, and since most clinical trials do not include the enrollment of geriatric patients, many medication risks within this population have not been evaluated within phase I through III clinical trials. ADRs are a significant concern in geriatric care, contributing to hospitalizations, morbidity, and mortality, and in fact, this population is at highest risk due to the increased levels of polypharmacy (the concurrent use of multiple medications). Polypharmacy is also a factor in the higher risk of falls in the elderly; this has serious consequences for elderly patients physically and psychologically, as well as increasing the overall cost of their care. However, coupling PGx testing with known drug-drug interaction data is helping to address these challenges, offering several benefits that can enhance the safety and quality of life for geriatric patients as well as managing their healthcare costs (Thomas et. al 2014).
Pharmacogenomic testing is helping to address these challenges, offering several benefits that can enhance the safety and quality of life for geriatric patients (Thomas et. al 2014).
One of the most significant advantages of PGx testing within geriatric medicine is the ability to personalize medication regimens by selecting the most appropriate medications and dosages for each patient based on their genetic profiles and coupling this with longitudinal biomarker clinical testing that is appropriate for their age. This approach is minimizing the trial-and-error process often associated with prescribing, and thereby reducing the time and discomfort associated with finding the right medication. All of this is enabling clinicians to avoid medications that are more likely to be ineffective or cause adverse reactions and reduce the number of medications taken by each patient.
Managing polypharmacy is a critical aspect of geriatric care, and therefore using PGx-driven insights, clinicians are making informed decisions about which medications to prescribe, discontinue, or adjust, based on the patient’s genetic profile (Brixner et. al. 2016). This personalized approach is reducing the risk of drug-drug interactions and streamlining medication regimens, making them more tolerable for patients and more manageable for their caregivers (Liu et. al. 2018). The result is improved patient safety and enhancement of their overall quality of life by reducing hospitalizations and the associated physical and emotional burdens that this brings (Lavan and Gallagher, 2016).
Numerous studies have demonstrated the benefits of pharmacogenomic testing in improving medication safety and efficacy in geriatric patients.
Warfarin and CYP2C9/VKORC1 Testing
Warfarin, a commonly prescribed anticoagulant, has a narrow therapeutic index and significant variability in dosing requirements among individuals. Variants in the CYP2C9 and VKORC1 genes can affect warfarin metabolism and sensitivity. Pharmacogenomic testing for these variants can guide dosing, reducing the risk of bleeding and thromboembolic events. Studies have shown that patients whose warfarin therapy is guided by pharmacogenomic testing achieve therapeutic INR levels more quickly and have fewer adverse events compared to those on standard dosing protocols (Johnson et. al. 2011).
Clopidogrel and CYP2C19 Testing
Clopidogrel, an antiplatelet medication used to prevent cardiovascular events, requires metabolic activation by the CYP2C19 enzyme. Genetic variants in CYP2C19 can reduce the effectiveness of clopidogrel, increasing the risk of cardiovascular events. PGx testing can identify patients who are poor metabolizers and may benefit from alternative antiplatelet therapy (Kanuri and Kreutz, 2019). Clinical trials have demonstrated that personalized antiplatelet therapy based on CYP2C19 genotyping improves clinical outcomes in patients undergoing percutaneous coronary intervention.
Antidepressants and CYP2D6/CYP2C19 Testing
Depression is a common and growing problem in the elderly population, and antidepressants are now frequently prescribed. Genetic variations in CYP2D6 and CYP2C19 can influence the metabolism of many antidepressants, affecting their efficacy and risk of side effects. PGx testing can guide the selection and dosing of antidepressants, improving treatment response and reducing the incidence of adverse effects. Studies have shown that pharmacogenomic-guided therapy can enhance the management of depression, particularly in patients who have not responded to standard treatments (Forester et. al. 2021; Cristancho et. al. 2019; Chang et. al. 2018).
Integrating PGx testing into routine clinical practice for geriatric patients requires several considerations, such as education, infrastructure, and cost-effectiveness (Klein et. al. 2017).
Healthcare providers need education and training to interpret PGx test results and apply them to clinical decision-making. This includes understanding the genetic variants associated with drug metabolism and response, as well as the evidence supporting pharmacogenomic-guided therapy. Continuing medical education programs and specialized training can help clinicians stay updated on the latest advancements in pharmacogenomics. Incite Health is helping to break down this barrier for PGx testing by providing simple and easy to implement reporting that clinicians can feel confident in incorporating into their patient’s care. Our PGx reports only include CPIC, PharmGKB and FDA-recognized guidelines, that can be updated at any time as new drugs are profiled.
Implementing PGxc testing in clinical practice requires appropriate infrastructure, including access to genetic testing laboratories and electronic health records (EHRs) that integrate PGx data. Collaborations between healthcare providers, geneticists, and pharmacists can facilitate the interpretation and application of test results. Additionally, ensuring equitable access to PGx testing, particularly for underserved populations, is essential to maximize its benefits. To this end, there is an increasing push to integrate PGx profiling as standard of care in long-term care facilities (Sugarman et. al. 2016) and home health patients (Elliott et. al. 2017).
The cost of pharmacogenomic testing has been a barrier to its widespread adoption. However, a growing number of studies are showing that it can be cost-effective in the long term by reducing adverse drug reactions, hospitalizations, and the overall cost of care. Health economic analyses are demonstrating the cost-effectiveness of PGx testing in geriatric populations and inform policy decisions regarding reimbursement and coverage (Glynn et. al. 2011; Youssef et. al. 2021, Rigter et. al. 2020) and help keep patients out of the hospital (El Morabet et. al. 2018)
The field of PGx is rapidly evolving across all areas of medicine, with clinical research aimed at expanding our understanding of the genetic basis of drug response and developing new testing technologies. Current PGx tests typically focus on well-characterized genetic variants associated with drug metabolism. However, ongoing research is identifying additional genetic factors that influence drug responses, including rare variants and genetic interactions that may be found in specific demographic populations. Expanding genetic panels to include a broader range of variants will enhance the predictive power of PGx testing and provide more comprehensive guidance for personalized therapy.
PGx is just one aspect of the broader field of personalized medicine, which includes other omics technologies such as proteomics, metabolomics, and transcriptomics. Integrating data from these complementary fields can provide a more complete and holistic understanding of an individual’s health and drug response, further refining personalized treatment strategies.
To maximize the impact of PGx testing in geriatric care, further clinical evidence and implementation science are needed. Real-world studies, such as many of those referenced in this blog, are providing insights into the effectiveness of PGx-guided therapy in diverse patient populations and clinical settings. By embracing this innovative approach, healthcare systems can better meet the needs of an aging population and ensure that geriatric patients receive the safest and most effective treatments available, while managing healthcare costs, reducing polypharmacy and the burden on carers (Hilmer and Gnjidic 2008; Maher et. al. 2013; Berm et. al, 2016).
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