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Study shows gene-drug interactions are common

Sep. 2, 2021, 8:36 AM


by Paul Govern

When a drug or combination of drugs causes different responses in different people, genetic variation is often at play. Pharmacogenomics, through discovery of genetic risk and use of clinical genotyping, aims to reduce trial-and-error approaches to drug prescribing.

Per the U.S. Food and Drug Administration, 103 drugs distributed in this country have reported pharmacogenomic associations that might affect therapy. It’s estimated that more than 90% of people carry at least one actionable pharmacogenetic variant.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) has so far identified 60 so-called level A drugs: those for which prescribing decisions stand to benefit most clearly from a patient’s genetic information. At 11 IGNITE Network-affiliated health systems, researchers with the IGNITE Pharmacogenetics Working Group counted exposures among adult patients to 36 of these drugs using an earlier, shorter list of level A drugs from CPIC. In the period under study, 2011 through 2016, these health systems collectively saw 7.2 million adult patients per year. The team’s report appears in Clinical Pharmacology and Therapeutics.

Prevalence of adult patients exposed to at least one of the 36 level A drugs ranged from 15.7% in 2011 to 17.7% 2014. Combining exposure data with the applicable genetic variant frequencies, the researchers estimate that, among all patient encounters with prescribing potential, 4.7% of encounters involved patients harboring genetic variants known to interact with, and change prescribing guidance for, a level A drug prescribed in the encounter.

Josh Peterson, MD, MPH

“While our sample included some of the nation’s larger academic health systems, it’s nonetheless likely that relatively few of these patients were genotyped for their drug response ahead of receiving these drugs,” said one of the report’s senior authors, Josh Peterson, MD, MPH, professor of Biomedical Informatics and Medicine at Vanderbilt University Medical Center and director of VUMC’s Center for Precision Medicine.

“Across the health care system, genotyping remains underutilized as a strategy to improve prescribing,” he said. “We hope that, with this report, physicians and health care payers will begin to take more notice of the broad opportunity available to personalize therapy. Our results show multigene pharmacogenetic panels can help across all adult age ranges and for a wide selection of drugs. With the count of CPIC level A drugs having risen to 60, the opportunity has only gotten larger.”

VUMC is among five IGNITE research centers funded by the National Institutes of Health (NIH). Peterson is a VUMC co-principal investigator, with Sara Van Driest, MD, PhD, associate professor of Pediatrics and Medicine, for an IGNITE Network pragmatic clinical trial investigating use of pharmacogenomics for prescribing antidepressants and opiates.

Others from VUMC on the study of level A drug exposures include Van Driest, Henry Ong, PhD, Jonathan Schildcrout, PhD, Yaping Shi, MS, and Leigh Anne Tang. The study was funded in part by the NIH (HG007253, TR000445).

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