Study pitches customized medication

Instead of prescribing drugs based solely off patients’ medical records, Pitt’s Philip Empey is looking into a new tactic — basing prescriptions on patients’ DNA.

Empey, assistant professor of pharmacy and therapeutics at Pitt’s school of pharmacy, is heading a UPMC initiative to start a larger trend of personalized prescriptions by taking genetic blood tests for cardiac catheterization patients.

Since December, Empey offers the genetics test to UPMC Presbyterian patients who undergo cardiac catheterization, a surgery to open arteries, and receive a stent to keep the artery open. So far, Empey said 150 cardiac catheterization patients have elected to get the test, which doctors then use to write genetic-specific prescriptions for blood thinners, which would eliminate complications associated with the drugs.

The University of Pittsburgh Clinical and Translational Science Institute, the National Institutes of Health, the McCune Foundation and the American Society of Health-System Pharmacists are funding the initative.

This part of the initiative — an effort to individualize medicines called Pharmacogenomics-guided Care to Improve the Safety and Effectiveness of Medications, or PreCISE-Rx — will test patients’ genetics to determine potential risks for side effects associated with blood thinners and adjust their medication accordingly.

“Most drugs, such as antibiotics, psychiatric medications and painkillers, don’t work for everybody. As we learn more about the genetic, environmental and other factors that shape drug metabolism, the current one-kind-fits-all approach will give way to personalized and more effective treatments,” Empey said in a UPMC release.

Empey said patients’ blood samples undergo genetics tests, which Magee-Womens Research Institute researcher Aleksandar Rajkovic developed and verified. The test reads a patient’s blood for the amount of a certain enzyme — which is required to activate clopidogrel, a common blood thinner commercially named Plavix — and helps doctors determine if the drug would be a good fit for that patient.

“Some people have different amounts of this enzyme,” Empey said. “Increasingly, we are able to pinpoint gene variations and other factors that affect how patients metabolize drugs, allowing us to more precisely target the right drug for the right patient.”

Rajkovic said the tests help to determine which individuals are at the highest risk for blood clots after a cardiac catheterization. Complications with blood thinners can lead to a regressive side effect, in which blood clots build up instead of breaking away, or other negative side effects.

Even though the initiative targets cardiac catheterization patients, Rajkovic said doctors could use genetic-specific prescriptions in different fields of medicine.

“Adverse drug reactions affect millions of patients in United States, may lead to re-admissions, longer hospital stays and, in most extreme cases, death,” Rajkovic said. “The goal of personalized medicine is to optimize medical care based on individual’s genetic information.”

According to Dr. Jeremy Berg, director of the Institute for Personalized Medicine at Pitt, genetic factors impact a drugs’ effects. The Food and Drug Administration has a list outlining those factors for about 150 drugs, including Plavix, a blood thinner commonly used for patients after they undergo cardiac catheterization.

Ten percent of Plavix users have complications because of their genetic makeups, and 30 percent of users cannot metabolize the drug properly, which causes the drug to have adverse or inconclusive effects.

Plavix prevents blood clots by blocking platelet aggregation and clotting pathways, according to Berg.

According to Empey, the results of the blood tests come back in about a day after the sample undergoes testing at Magee-Womens Hospital of UPMC.

Rajkovic said the test can identify patients with poor and enhanced metabolization of Plavix. The test involves extracting and purifying DNA from a patient blood sample to find nucleotide changes in the DNA. These changes — called polymorphisms — can show the effect on the enzyme that activates the drug’s function.

“We are presently adjusting patient’s dosage of Clopidogrel, based on CYP2C19 [enzyme] gene testing, to maximize their recovery following cardiac catheterization,” Rajkovic said.

Berg said if doctors can base prescriptions on genetic factors in the future, there will be less people taking drugs that have only adverse effects, no benefits. He said doctors are beginning to explore the use of genetics tests in cancer treatments, as well as blood thinners.

“All tumors are genetically different, and we can sequence them to figure out what drugs and therapeutic treatments will work best,”  Berg said.

Empey said he hopes the project will see about 700-750 patients before the study closes at the end of 2016.

“We hope to be able to do this for a lot more drugs,” Empey said. “Many medications have genetic information associated with them. Just not all are ready to be used clinically.”