Frontline Medical News

EXPERT ANALYSIS AT ICOO2015

BOSTON (FRONTLINE MEDICAL NEWS)Genetic tests for pain treatment efficacy are being marketed in the United States and Australia, but one expert argues that they are not ready for use in clinical practice.

There is evidence that variability in patient response to opioids is due to pharmacogenomics that define drug metabolism and receptor activity, but it is just one factor that cannot yet be teased out from others, according to a summary by one expert at the International Conference on Opioids.

“My view is that commercialization of current genetic tests of pain treatment efficacy with opioids is somewhat premature. Evidence is limited, and I think regulation is necessary,” said Dr. Andrew Somogyi, professor in clinical and experimental pharmacology, University of Adelaide (Australia).

Progress has been made in identifying genetic factors that influence response to opioids, but there are two barriers to clinically useful tools, according to Dr. Somogyi. One is that clinical utility has yet to be proven for any test in a well-designed trial. The other is that even if pharmacogenomics features are relevant, the quality of commercial tests must be validated.

There are now at least two companies marketing genetic tests to guide selection of analgesics in the United States as well as one in Australia, but Dr. Somogyi said that neither the U.S. Food and Drug Administration nor the Australian Therapeutic Goods Administration provides any regulatory oversight. He noted that prices for the testing vary, but he believes that there is no evidence that analgesia can be improved by acting on test results.

As an example, he noted that the company in Australia employs genetic predictors of CYP2D6 function, an enzyme important to opioid metabolism, to estimate benefit from this class of analgesics. However, published studies have not yet generated compelling evidence that this is clinically relevant for either improving pain control or avoiding adverse events.

In the case of oxycodone, studies comparing poor metabolizers to ultra-rapid metabolizers do show important differences in experimental models of pain, but “clinical studies have really shown no effect,” Dr. Somogyi said.

He drew the same conclusion about CYP2D6 function in regard to the effects of codeine and the variants in the OPRM1 gene and their effect on the Mu receptor and response to morphine. In all cases, there are studies to suggest genetic differences are meaningful in experimental models, but no evidence from a clinical study to show that acting on this information changes outcome or otherwise improves care.

Although he acknowledged that it is tempting to believe pharmacogenetics can explain the well-known variability in response to analgesics, “other factors are just swamping these pharmacogenetics variables,” Dr. Somogyi maintained. Not least of these other factors are the psychosocial factors that influence response to pain stimuli.

This does not preclude an eventual role for pharmacogenetics in the selection of analgesics. Dr. Somogyi, who has been working in this area for several decades, outlined a broad array of promising areas of research. It is the current clinical application of pharmacogenetics with which Dr. Somogyi took issue. He criticized many of the marketing claims made on behalf of available tests, which he considers unsubstantiated.

Deferring to the expertise of Dr. Somogyi, Dr. Paul A. Sloan, professor and vice chair for research, University of Kentucky, Lexington, said he found the perspective compelling. In an interview, Dr. Sloan, cochair of the 2015 ICOO meeting, reported that he knows of no one using pharmacogenetics testing to guide analgesic choice, and he reiterated Dr. Somogyi’s concerns about the need to validate the quality of tests as a part of an effort to confirm their viability as clinical tools.

Dr. Somogyi reported having no financial disclosures.

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