To Demonstrate Precision Medicine Utility, Focus on Pharmacogenetics Studies and Data

Three pharmacogenetics studies and clinical investigations have demonstrated precision medicine efficacy. Their focus in pain management, cardiovascular health, and infant healthcare offers insights toward three niche approaches for hospitals and health system leaders considering a precision medicine initiative.

Oncology gets the lion's share of attention when it comes to advances in precision medicine. That is no wonder, given the clinical utility we read about almost daily. But don't be fooled into thinking that significant inroads are limited to cancer treatments.

A precision medicine team at the University of Florida (UF), including Michael Clare-Salzler, MD, Chair of Pathology, is involved in multiple clinical investigations where precision medicine efficacy has been demonstrated.

One involves the use of gene-guided opioid therapy for pain control. Another involves genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). And one of the most noted examples is the work done at Rady Children's Hospital in San Diego, where rapid whole-genome sequencing has been shown to diagnose genetic disorders in infants, in time to improve treatment.

Michael Clare-Salzler MD

Michael Clare-Salzler, MD (above), Chair of Pathology at the University of Florida School of Medicine, offers insights about three niche approaches to undertaking a precision medicine initiative and key points of a sampling of pharmacogenetics studies.
(Photo copyright: University of Florida Health.)

Here's a summary of three pharmacogenetics studies, and why they are important:

Pain control in the primary care setting. The precision medicine team, including Larisa Cavallari, PharmD, Associate Professor, University of Florida Department of Pharmacotherapy and Translational Research; Julie Johnson, PharmD, Dean and Distinguished Professor, University of Florida College of Pharmacy, and Clare-Salzler, has successfully demonstrated that CYP2D6-guided opioid therapy can improve pain control in the primary care setting. Operating on the premise that CYP2D6 genotype affects bioactivation of codeine and tramadol-thus conferring poor pain control to immediate and poor metabolizers-the research team enrolled participants with chronic pain who received either gene-guided (n=235) or usual (n=135) opioid prescribing. They evaluated pain at baseline and 3 months later. Among 45 intermediate or poor metabolizers who were initially prescribed tramadol/codeine, nearly one-third who received CYP2D6-guided therapy reported clinically meaningful pain improvement, versus none in the usual care group. No such difference was seen in the normal metabolizers who received either treatment.

Antiplatelet therapy after PCI. In a study led by the UF precision medicine team, the NIH-funded IGNITE Network also aimed to determine outcomes with genotype-guided antiplatelet therapy after PCI. Armed with the knowledge that CYP2C19 loss-of-function alleles weaken the efficacy of clopidogrel after PCI, investigators sought to determine the impact of gene-guided therapy after PCI. They evaluated more than 1,800 individuals, ~one-third of whom had a loss-of-function allele. After genotyping, participants with the allele were given either clopidogrel (n=226) or alternative antiplatelet therapy (prasugrel, ticagrelor; n=346). The clopidogrel group was more than twice as likely to experience major adverse cardiovascular events (i.e., heart attack, stroke, or death). Moreover, the risk of adverse cardiovascular events in patients without the loss-of-function allele (most of whom received clopidogrel) and those with it who received alternative treatment was similar.

Diagnosing genetic disorders in infants. Rapid whole-genome sequencing (rWGS) has been demonstrated to diagnose genetic disorders in infants, in time to change medical or surgical management. Researchers conducted a retrospective cohort study involving 42 families who received rWGS (33 of whom also received 144 standard genetic tests). Diagnostic sensitivity was significantly better with rWGS (43%) than with standard testing (10%). rWGS led to changes in medical or surgical management in nearly one-third of the infants who received it. Care was changed in only one infant as a result of standard testing.

Clare-Salzler, a member of the Precision Medicine Institute's advisory board, suggests that there are lessons to be learned here for hospital and health system leaders seeking to launch or accelerate their own precision medicine programs. "At UF we focused on pharmacogenetic studies impact hospitalizations and rehospitalizations, a very important issue for hospitals these days. A key to success of these programs will be to demonstrate improved health and outcomes and, importantly, reducing the cost of health care.

A well-conceived precision medicine program starts there, he notes. "We did that with the study on cardiac stents," and it was well received.

The bottom line: Start with a niche area where you can reasonably expect costs savings and improved outcomes in the population you serve. "Our goal is to reduce the cost of healthcare and improve it," concludes Clare-Salzler. "We operate from that basic foundation."

-Dean Celia

Related Information:

CYP2D6-guided opioid therapy improves pain control in CYP2D6 intermediate and poor metabolizers: a pragmatic clinical trial

Multi-site Investigation of Outcomes with Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy after Percutaneous Coronary Intervention

Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization

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