In the late 1990s and early 2000s, health care providers and researchers noticed that some HIV-infected people (approximately 5%) developed severe hypersensitivity reactions to the drug abacavir, which in some cases caused more Organ failure, anaphylactic shock and even death. They are eager to determine why only certain patients are affected so that they can continue to prescribe this highly effective therapy while minimizing the risk of potential harm. Early research Providers are urged to closely monitor patients taking abacavir and stop treatment when there are signs of reaction.
Researchers set out to investigate whether genetic variation or polymorphism is related to hypersensitivity to abacavir. By early 2002, First Learn Published an article linking mutations to abacavir hypersensitivity. Today, all patients must undergo genetic testing for high-risk genetic variants before starting treatment with abacavir.
These discoveries are important milestones in the emerging and rapidly developing field of precision medicine, which has identified many other associations between genetic variation and optimal drug response or adverse reaction characteristics. More specifically, the field of pharmacogenetics uses the results of patients’ genetic tests to determine the most effective and lowest-risk drug therapies to suit their personal circumstances, which has become an increasingly recognized prescription decision-making optimization strategy.
An emerging field
Every year there are more discoveries about how our DNA affects our response to drugs. The accumulation of these data is so fast that the FDA now provides two information resources for prescribers: Pharmacogenomic biomarker table in drug labeling and a Pharmacogenetics Association Table, Which lists gene-drug interactions that the agency has determined that there is sufficient scientific evidence to show that there are differences in drug response based on genes. However, these lists cover different aspects of drug genetic information. Although there is some overlap between resources, the scope of information is different and not comprehensive.
The main reason why my pharmacist colleagues and I decided to review, analyze, and decompose the information in FDA resources was to get a more complete and organized view of drug genetic information. We divide the drug genetic information cited in the table into seven categories, which describe the nature of drug-gene interactions. In addition, we also determined whether the gene is known to affect drug safety (risk of adverse reactions), drug efficacy (risk of reduced effectiveness), or neither. Research, “Pharmacogenetics information characterization and pharmacogenetics association table in the drug label of the Food and Drug Administration,” published in a peer-reviewed journal Drug Therapy Yearbook.
We hope to have a structured and systematic approach to review pharmacogenetics information in order to fully understand the nature of the information and its potential clinical impact. This can lay the foundation for constructing meaningful drug genetic information into the clinical decision-making process of prescribers. after all, Only 9% of primary care doctors The report ordered a pharmacogenetics (PGX) test based on the 2020 survey results, and less than 4% of people reported that they were confident in their ability to interpret the results. However, at the same time, 80% of respondents said that they may or are very likely to consult a pharmacist trained in pharmacogenetics to help interpret the report. Educating all stakeholders on pharmacogenetics information and incorporating such information into clinical decision support guidelines will help protect more patients and improve outcomes.
Driving safe and effective decision-making
Clinicians have limited time, and PGX test result reports are often lengthy and complicated, so it is not surprising that few survey respondents are eager to include such information in their decisions. The FDA provides pharmacogenetics information, but again, few providers have time to carefully review its relevance to their individual patients.
Our research attempts to provide an organized view of the types and results of clinically relevant FDA review of pharmacogenetic information. We analyzed the FDA-approved individual prescription information listed in the Drug Labeling Biomarker Table (first published in 2008) and the Pharmacogenetics Association Table (first published in 2020). The U.S. Food and Drug Administration created the latter form in response to the statements of some pharmacogenetics testing companies that “do not receive adequate scientific support.” According to a statement from the agency.
Our review started with more than 400 drug-gene pairs, but once we eliminated drug-gene pairs and the information did not describe the impact of genetic variation on drug disposal or response, our list was reduced to 308 pairs. Although most of the drugs studied are used in oncology, these drugs span a variety of other therapeutic areas, including psychiatry, neurology, infectious diseases, and cardiology. Our drug genetic information categories are:
- Polymorphism affects drug metabolism
- Polymorphisms affecting drug delivery
- Polymorphisms affecting the direct protein targets of drugs
- Variants associated with increased susceptibility to adverse drug reactions
- Variations associated with poor treatment
- Drug indications defined by biomarkers
- Adverse drug reactions as defined by biomarkers
Almost all (97%) drug gene pairs are associated with biomarker-defined drug indications (36%), polymorphic drug metabolism (33%), or increased susceptibility to adverse reactions (28%). Examples of the latter category include individuals carrying the HLA-B *57:01 gene at increased risk of abacavir hypersensitivity, or individuals lacking an enzyme (glucose 6-phosphate dehydrogenase) at increased risk of hemolytic anemia. Our characterization shows that 87% of drug-gene pairs are related to safety or efficacy-related outcomes, and most drugs are only affected by a single gene variant.
just started
We expect that in the near future, pharmacogenetics data will become commonplace in prescription selection decisions. More and more studies have demonstrated the “clinical utility” of incorporating gene-based recommendations into prescription decisions, thereby making genetic testing more accessible, and healthcare payers are more willing to support testing coverage and reimbursement. Of course, genetic information is used to drive some decisions today, but the relevance and quality of the data are only part of the reason for its limited adoption so far.
Prescribers need a pharmacogenetics knowledge base to determine safe and effective drugs and dosages for their patients, but they also need pharmacogenetics test information to be easily accessible, interpretable, and meaningful. Our research is just one of many steps to address the challenge of providing pharmacogenetic information at or near the time of ordering so that prescribers can easily and effectively make the best treatment decisions for patients.
Photo: ipopba, Getty Images
