Pharmacogenomic Testing Could Reduce Adverse Effects, Therapeutic Failure in MHS

But Resource Remains Underutilized

SIOUX FALLS, SD — Pharmacogenomic testing is an underutilized resource in the Military Health System (MHS) that could reduce adverse drug events and therapeutic failure. Based on evaluations of pharmacogenomic prescription data, a significant number of MHS beneficiaries taking related medications might be predicted to have non-normal metabolism and be at increased risk for adverse drug events or therapeutic failure, according to a recent study.

The research published in Military Medicine used MHS prescription data along with available genotypic and phenotypic population frequency data to estimate the potential impact of pharmacogenomic testing in the diverse MHS patient population.¹

Pharmacogenomic testing, which analyzes how a person’s genetic makeup may affect how their body processes certain medications, is often completed after an adverse drug event. However, doing preemptive testing rather than reactive testing could potentially decrease preventable drug-related hospitalizations and positively impact combat readiness. Prior studies have suggested that pharmacogenomic testing may be beneficial in individual patient medical management, but there’s limited research on the potential impact of preemptive pharmacogenomic testing in the MHS.

Study authors are affiliated with Augustana-Sanford Genetic Counseling Program in Sioux Falls, SD; Uniformed Services University of the Health Sciences in Bethesda, MD; and Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. in Bethesda, MD.

In their retrospective cross-sectional study, researchers used fiscal year (FY) 2021 prescription data from the Defense Health Agency (DHA) Pharmacy Operations Division. In their analyses, they included medications that had Clinical Pharmacogenetics Implementation Consortium (CPIC) level A, A/B and B designations that were prescribed to active duty, reserve, retired and dependent MHS beneficiaries ages 18 and up.

The study evaluated prescription count, age, biological sex and MHS beneficiary status for medications prescribed within the MHS and then estimated the number of MHS beneficiaries predicted to have non-normal metabolism of a given pharmacogenomic testing-related medication. Data were presented as a range based on the CPIC allele and metabolizer frequency data, which vary across Pharmacogenomics Knowledge Base-defined biogeographical groups, according to the authors.

The investigators found there were more than 8 million unique prescriptions for 83 pharmacogenomic testing-related medications with CPIC level A, A/B or B designation in FY21. Of these prescriptions, over 1.2 million prescriptions (15%) were for active duty and reserve members. The top five prescribed pharmacogenomic testing-related medications for active duty members were ibuprofen, ondansetron, hydrocodone, omeprazole and meloxicam.

In addition, the researchers further analyzed 64 medications with known metabolism frequency data, and in FY21, there were up to 632,974 MHS beneficiaries taking omeprazole who were predicted to have non-normal CYP2C19 metabolism. Omeprazole had the highest number of prescriptions among individuals with estimated non-normal metabolism, the study authors pointed out.

Among medications with a risk for severe adverse drug event, allopurinol was the most common, with up to 301 prescriptions provided to active duty members estimated to have the *58:01 variant, which is associated with increased risk for toxic epidermal necrolysis, the researchers explained.

The authors concluded that pharmacogenomic testing is an underutilized resource in the MHS system, even though many pharmacogenomic testing-related medications with actionable CPIC guidelines are widely prescribed among MHS beneficiaries. Based on published allele and metabolizer frequencies in the general population, a significant number of MHS beneficiaries taking these medications may be predicted to have non-normal metabolism and be at increased risk for adverse drug events and/or therapeutic failure.

Because of high prescription counts across all MHS beneficiaries, including active duty members, the investigators suggested that pharmacogenomic prescription data should be used to implement preemptive pharmacogenomic testing in the MHS. Clinicians should aim to reduce adverse drug events and therapeutic failure to improve readiness among servicemembers.

“I recommend that prescribing professionals consult with their pharmacist team to see if their clinic has access to pharmacogenomic tests (PGx), which may provide information on what types of medications may be most effective for their patient and/or what medications may decrease the risk of an adverse event,” Rachel Zigler, M.S., CGC, corresponding author of the study and a certified genetic counselor at Augustana-Sanford Genetic Counseling Program, told U.S. Medicine.

“With any genetic testing, I strongly encourage that the provider and patient have a conversation about what the testing is looking at and the types of results they may receive,” Zigler suggested.

While Zigler didn’t have information about the frequency of pharmacogenomic testing in the MHS, she noted the VA’s Million Veteran Program might look at some of the known genes related to medication metabolism, as well as genes related to other health conditions. Zigler recommends for patients to speak with a genetic counselor prior to doing this testing.

“If a provider is interested in ordering this testing for their patient, I would recommend that they speak with a PGx pharmacist or a genetic counselor who is familiar with PGx testing to help answer some of their questions,” Zigler said. “A large takeaway from this study is that there are medications being prescribed via the MHS that have known PGx guidelines, and, by utilizing PGx testing, the provider may learn more information on what medications could increase the risk of therapeutic failure or adverse events in their patient.”

 

1. Zigler R, Pagani A, Haigney M, Berninger T, Hellwig L. Evaluating Pharmacogenomic Prescription Data in the Military Health System. Mil Med. 2026 Feb 14:usaf652. doi: 10.1093/milmed/usaf652. Epub ahead of print. PMID: 41689549.