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Wednesday, May 25, 2022

Genetics Affect Drug Reactions in Older Adults

Increasingly, patients with Alzheimer’s, cancer, depression, chronic pain and cardiovascular disease are getting genetic testing to personalize and optimize their quality of care.  

Pharmacogenetics, also known as pharmacogenomics, is the study of how genes affect an individual’s response to drugs. Genetic testing searches for changes or variations in genes that may signal which medication might be the most effective or have fewer side effects for a particular patient.

Genomic Testing

For example, scientists have been working to understand why antidepressants help some people but don’t work for others. Humans use cytochrome P450 enzymes to process medications. These enzymes vary in different people due to inherited (genetic) traits, causing medications to affect each person differently. Your doctor can use a cytochrome P450 (CYP450) test to investigate how your body metabolizes a certain drug. The test can provide information about how you may process different medications.

Poor metabolizers have less active or inactive alleles, which are gene variations caused by chromosomal mutations. This places them at a higher risk of overdosing or experiencing an increase in toxicity with some drugs. On the other hand, ultra-rapid metabolizers can experience a lack of drug efficacy because medicine leaves their body too quickly, before they can work as intended. However, prodrugs such as clopidogrel and codeine can induce the opposite reaction after metabolization.

CYP450 2D6 Testing Available

It is possible to get a genotyping test via the internet. PUSH Health uses a licensed medical provider and Quest Diagnostics labs to collect information and samples. Results are delivered electronically in about four business days for a total of $154.51, which is typically paid privately. (Check first to see if your health insurance provider will cover the cost of any needed testing. Some do.)

The PUSH Health website states that the test checks for proteins that may play a role in “hormone, cholesterol and vitamin D metabolism,” and that the test can also “help with managing dosing for medications treating mood disorders.”

Genotyping tests like CYP450 are used in other areas of medicine too. A CYP2D6 test is valuable in determining which cancer drug, such as tamoxifen for breast cancer, is likely to be most effective for treatment. The CYP2C9 test can help doctors pinpoint the right dose of the common blood thinner warfarin to avert dangerous side effects. 

Drugs Often Ineffective, Dangerous

While 4 billion prescriptions are written every year in the US, only about half demonstrate the expected therapeutic efficacy. Adverse drug reactions (ADRs) are the fourth leading cause of death and cost an estimated $136 billion annually. According to research, genetic factors can impact up to 95% of a person’s drug response and are estimated to be a factor in up to 20% of total reported ADRs.

Furthermore, the COVID-19 pandemic forced growth in the field of personalized care and boosted demand for pharmacogenomics, as drugs were used before FDA approval, for compassionate use, or in clinical trials. In recent years, regulatory agencies worldwide, including the FDA, have approved the aggregation and dissemination of pharmacogenomic (PGx) information on hundreds of drug labels.

Use Still Infrequent

However, doctors are not always on board. In 2012, over 10,000 US physicians conducted a nationwide survey by US physicians revealing that although 97.6% of respondents agreed that genetic variations may influence drug response, only 10.3% felt adequately informed regarding pharmacogenomic testing. Additionally, only 12.9% of the doctors had ordered such a test in the last six months, while 26.4% anticipated doing so in the next six months. Only 29% of all respondents had received any education in the field. Those who had were more likely to incorporate testing in their practice. 

A 2019 study did not find much progress. Researchers noted that 

“in the last years, health authorities such as Health Canada and the FDA have set PGx biomarker information on labels of over 100 and 200 drugs, respectively. Despite these recommendations, the use of PGx testing in routine clinical care remains infrequent. Reasons that explain the slow uptake of PGx in clinics include unfamiliarity of health care providers with PGx, cost associated with testing, time constraints, absence of clear clinical guidelines, lack of easily accessible tests, and several ethical considerations."

Technological Advances Enable Genotyping

It is only recently that the field of pharmacogenetics was made possible by advances in genetic research and data gathering. Electronic medical records (EMRs) have provided a massive influx of statistical data that has barely begun to be mined, covering symptoms, diagnostics, biomarkers, therapy, and adverse effects. . In the future, artificial intelligence will enhance discovery and impact everything from medical devices to lifestyle management solutions. 

The role of PGx in therapy optimization is continuously evolving. Currently, some applications have proven very effective. One such application is dosing for the anticoagulant warfarin, in which 60% of individual variability in dosing can be explained by the analysis of three enzymes, combined with an individual’s age and weight.

In fact, a 2016 review of 80 studies found that 55% of those studies showed that PGx testing was cost-effective, 16% demonstrated that PGx was cost-saving, and 13% showed it was cost-dominant, defined as being both cost-saving and clinically beneficial. 

One challenge that remains is implementing PGx testing on a broader level so that patients could present the information to healthcare professionals as a matter of course. The goal would be to prescribe the right drug for the right patient more often. Additionally, it would generate an enormous sum of data to improve research outcomes and speed quality and cost-effectiveness. 

The quickest route to improved PGx testing is, in appropriate circumstances, for patients to request it, healthcare professionals to use it, and healthcare facilities to incorporate its use in care.