Understanding the Impact of Pharmacogenomics in PACE

PACE was designed to care for the most complex patients in the frail and elderly community. Since PACE participants tend to have comprehensive medical conditions or comorbidities, many require polypharmacy solutions. However, no two people are the same. We all have different genes and different factors at play. This means not every medication will work for every person.

Understanding why certain drugs will or won’t work for a participant is the key to creating more effective medication regimens. We need to focus on how to better prescribe, or even deprescribe, and make informed decisions that optimize patient outcomes and reduce adverse drug events.

Enter pharmacogenomics (PGx).

Before we go any further, let’s start at the beginning and break things down.

1. What is PGx?

PGx assesses the impact of genetic factors on an individual’s response to certain medications.

2. How does PGx work?

Each person has certain genes that code for drug metabolizing enzymes. Those enzymes have a range of activity or expression, and based on their expression, a phenotype is assigned. That phenotype could be a poor, intermediate, normal, rapid, or ultra rapid metabolizer.

If a patient is a poor metabolizer, there are drugs their body won’t be able to break down due to enzyme inactivity. This could increase the risk for side effects. If a patient is an ultra-metabolizer, they might break down certain drugs too fast due to increased enzyme activity. This could increase the risk for therapeutic failure.

Simply put, if a patient is taking a medication, but the gene and receptor don’t match, there is a chance that patient is only getting partial benefits of that drug, while the other part is a side effect of the medication.

3. What is phenoconversion and how does it affect PGx?

PGx helps pharmacists and prescribers identify drug-gene interactions, but there are other external factors that influence an individual’s response to certain medications. When a patient is on several medications, which is typical of PACE participants, they can affect how each medication is metabolized, leading to drug-induced phenoconversion. Phenoconversion is essentially a mismatch between an individual’s genetically derived phenotype and their actual capacity to breakdown or activate a drug.

For example, if an individual was a normal metabolizer, they would expect to have a standard response to Drug X. However, if they were also taking Drug Y, which had a greater affinity to bind to an enzyme, Drug X would have to wait until Drug Y completed its metabolism. Eventually, there could be a buildup of Drug X, which could lead to an increased risk of side effects. Even though this individual is a normal metabolizer, their body is reacting as if they were an intermediate or poor metabolizer.

Many PACE centers across the country have started using PGx to inform participant care. PGx testing is a process that requires collaboration between PACE providers and PGx clinical pharmacists. At Beacon of Life in New Jersey, Medical Director, Dr. Eric Glantz, and his team have monthly polypharmacy meetings to discuss options for certain participants. They take a look at each participant’s history and current medication regimen to determine if he or she would be a good candidate for PGx clinical services.

Immanuel, a PACE Center in Omaha, Nebraska, is currently in the midst of PGx trial across all its participants. Their team collaborated with CareKinesis to design a process that allows each and every participant to be tested over a period of time.

This process includes an algorithm that stratifies participants based on qualities such as types/number of medications taken and periodic assessments to determine appropriate individuals to undergo testing. After only a year, Immanuel has tested over half of its participants.

“I do see PGx and other pharmacogenomic testing integrating more into the approach of the care of any patient,” notes Dr. Devin Fox, Vice President of Clinical Operation at Immanuel.

Once a participant is identified as an appropriate candidate by their care team, the PGx test kit is ordered by a provider. The provider or healthcare professional then swabs the participant, follows the test kit instructions, and sends the kit to a Clinical Laboratory Improvement Amendments (CLIA)-certified lab for processing. Once the lab receives the specimen, results are processed and delivered.

Once the PGx results are in, a PGx specialized pharmacist will compare the results to the participant’s complete medication regimen and develop a report that addresses any drug-gene interactions, as well as drug-drug-gene interactions that result in phenoconversion.

The PGx specialized pharmacists provide clinical guidance in the report, then hand it off to the pharmacist who is closely collaborating with the participant’s medical team. That pharmacist can then incorporate patient specific factors into the report and develop personalized recommendations for the participant’s clinician.

Factors such as time of day, taken with or without food, or before and after other medications can alter the effectiveness of certain drugs and require simple changes. Medications are targeted based on available PGx guidance that could lead pharmacists to recommend a change in therapy. These medications include clopidogrel (an antiplatelet), opioids activated by CYP2D6, and certain antidepressants. All patient and medication-specific factors are thoroughly considered when creating a new, optimized medication regiment for a participant.

“We [CareKinesis pharmacists] support the providers the entire step of the way. We don’t just give results.” DeJesus remarks.

Once recommendations are made, there are still a few conversations that need to be had. First, the clinical pharmacists will meet with the provider to go over the findings and discuss what changes are recommended. Once a new plan is in place, the provider can have a meaningful conversation with the participant so they can fully understand what is changing and why.

The participant needs to understand the benefits of the regimen change and see that it isn’t just an attempt to remove a medication. Educating them is key. Everyone needs to be on board and on the same team.

Based on preliminary findings from participants that have completed PGx testing from Immanuel, about 80% of participants who were tested have a drug-gene interaction. About 50% of those participants experience phenoconversion.

“We took it a step further to see what opportunities the pharmacist would have to suggest a change to an alternative medication. We can target 40% of those participants to make a change. It’s pretty meaningful that our pharmacists can make actionable recommendations here,” recalls DeJesus regarding the CareKinesis PGx findings.

Beacon of Life initiated an opioid study using PGx testing on their participants with chronic non-cancer pain. Their team was motivated by the opioid epidemic to become smarter with prescribing and achieve better pain scores and outcomes for participants. The study revealed a decrease in pain score on participants who received PGx testing and followed the recommendations prescribed.

“Opioids as a pain medication is a low hanging fruit area where we often struggle to control patients’ pain,” Glantz explains. “Having the additional knowledge of which medication would achieve better outcomes or what medications are interacting with each other really helps to achieve better outcomes and smarter prescribing.”

Many success stories have come from changes implemented due to PGx findings. Positive results have included participants becoming more active, losing weight, experiencing less pain, mood improvements, positive outlooks, and even deprescribing all together.

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