Pharmacogenomics (PGx) has the power to revolutionize health care, save lives, reduce side effects, improve care outcomes, and save money. Illnesses like depression, which have high relapse rates and even higher rates of disability, are particularly ripe for PGx.
A 2018 study found a 22 percent higher remission rate among depressed patients who used PGx-guided treatment, as well as an average reduction in annual disease-related costs of $5,962. Despite promising clinical trials and compelling analyses, however, many healthcare systems have been slow to implement genetic testing. In 2018, that began to change. PGx has now emerged in the mainstream, with more systems than ever clamoring to access and implement pharmacogenomic data.
In 2018, new evidence and guidelines made it easier and more effective than ever before to integrate genetic testing into healthcare systems.
Supporting Ongoing Implementation Resources
Last year, the National Institutes of Health gave the Clinical Pharmacogenetics Implementation Consortium (CPIC) a $5 million dollar grant. The grant will fund expanded efforts to incorporate PGx into healthcare systems and electronic health records. The CPIC continues to support laboratories in their efforts to rapidly disseminate new knowledge that may fundamentally alter how medications are prescribed.
The CPIC currently offers more than 50 clinical practice guidelines that it has developed and approved since 2009. These guidelines are rapidly expanding. As researchers, institutions, and commercial entities join the field of PGx, sharing resources across systems and entities can help further expand the PGx toolbox.
New CPIC Guidelines
The CPIC aims to standardize PGx guidelines based on new and emerging evidence. As interest in PGx accelerates, so too might the implementation of new guidelines. CPIC guidelines are the gold standard for healthcare systems that use genetic testing, and the publication of a new guideline means the evidence for a drug-genome interaction is robust.
The CPIC approved two new guidelines in 2018. A guideline addressing interactions between CYP2D6 and tamoxifen suggests that certain CYP2D6 polymorphisms may alter drug metabolism. This results in lower endoxifen concentrations, elevating the risk of disease relapse among patients with early breast cancer.
A second new guideline points to interactions between RYR1 or CACNA1S and volatile anesthetic agents and succinylcholine. Patients with certain variants of RYR1 and CANA1S have an increased risk of malignant hyperthermia. This also increases the risk of life-threatening anesthetic reactions. Research suggests that this dangerous interaction occurs in 14 drug-genome pairs.
Updated CPIC Guidelines
The CPIC routinely updates their guidelines as new evidence emerges. The Consortium amended two previous guidelines in 2018. The 2017 guideline for DPYD and fluoropyrimidines recommended that the dosage for intermediate metabolizers of DPYD with an activity score of 1 be reduced by half. Those with activity scores of 1.5 should have a dose reduction of 25 to 50%. This latter guideline was based on limited evidence for PGx-guided dosing in patients with activity scores of 1.5
New research changed the guideline. The CPIC now recommends a dose reduction of 50 percent for all patients with an activity score of 1 or 1.5. The guideline also suggests that patients who are homozygous for the 2846A>T variant may need a dose reduction of more than 50 percent.
The second updated guideline addresses interactions between carbamazepine, oxcarbazepine, and the HLA genotype. Patients who carry the HLA-A*31:01 or the HLA-B*15:02 allele are significantly more likely to experience serious skin reactions in response to carbamazepine and oxcarbazepine. Documented skin reactions include Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), maculopapular exanthema, and toxic epidermal necrolysis.
The new guidelines recommend using an alternative drug for patients who have not previously taken carbamazepine or oxcarbazepine.
Organizations that implement CPIC guidelines will provide better quality patient care. TSI doesn’t just monitor these guidelines. Members of our team help write them. We support labs, healthcare systems, and clinicians in their efforts to implement PGx testing that draws upon reliable evidence, yielding actionable recommendations.