CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Dr. Cavallari
In genotyping of CYP2D6 alleles for opioid prescribing, intermediate or poor metabolizers do not get the analgesic effect of the opioid whereas ultra-rapid metabolizers may experience toxicity. As with CYP2C19, there was evidence that genotype influences drug response, existence of a CPIC guideline, and availability of alternative drug or dosing, but data on clinical utility of genotype-guided opioid prescribing were lacking.
When primary care physicians requested implementation of genotyping of CYP2D6 for codeine and tramadol in 2015, Dr. Cavallari and colleagues set up a prospective cluster design pragmatic trial to evaluate the effect of genotype-guided therapy on patient-reported pain outcomes. They enrolled 480 patients with chronic pain of more than three months duration. Genotyping showed that 10 percent were intermediate or poor metabolizers. After considering concomitant use of CYP2D6 inhibitors, 30 percent were intermediate or poor metabolizers. For those patients, alternative therapy was recommended in the EHR.
Changes in therapy within three months were made only 31 percent of the time they were recommended. “This was lower than what we’d like,” Dr. Cavallari says. She and colleagues understood why. “We collected genetic samples in the clinic and it took a week for the genotyping results to come back. The patients might not be returning to the clinic within the study period. So the availability of the genotyping result at the time of the practitioner and patient encounter was crucial.” This finding was the same for private practice sites.
Preliminary clinical outcomes data from this study were presented in March at the meeting of the American Society for Clinical Pharmacology and Therapeutics. Outcomes among intermediate and poor metabolizers in the implementation group taking codeine or tramadol at baseline were compared with those of similar patients in the control group. More patients in the implementation group had a clinically significant reduction in pain intensity compared with those in the control group—16 percent versus two percent—even though compliance with the recommendation to change was only 31 percent.
Based on these positive data from chronic pain patients, Dr. Cavallari and colleagues are about to start a trial in acute pain from hip or knee arthroplasty. “Patients have two visits prior to surgery. We will get a genetic sample at the first visit. The surgeon prescribes pain medication at the second visit. At that time genotyping data will be available,” she explains.
Dr. Cavallari has joined in gathering rigorous data for two gene-drug pairs. “I personally don’t think randomized controlled trial data are needed,” she says. “But some level of evidence of benefit is needed for clinicians and payers. We can’t afford to do clinical trials for every gene-drug pair.”
In some cases, she adds, such as HLA-B*1502 allele screening for risk of carbamazepine-induced Stevens-Johnson syndrome, “It would even be unethical.”
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William Check is a writer in Ft. Lauderdale, Fla.