Acccording to some reports deaths from painkiller overdoses have tripled over the last decade and led to the deaths of 14,800 Americans in 2008, exceeding those caused by heroin and cocaine combined. More recently, a 2011 GAO report linked prescription pain killers to a 142% spike in emergency room visits between 2004 and 2009. The increase in deaths from opioids has pushed drug poisoning ahead of automobile accidents to be the leading cause of accidental death in the United States. Painkiller sales have increased fourfold since 1999. Opioids, derived from the poppy plant, reduce the perception of pain by attaching to opioid receptors in the brain, spinal cord and elsewhere in the body.
While the Food and Drug Administration (FDA) has recently taken action by finalizing its Risk Evaluation and Mitigation Strategy (REMS) for extended-release/long-acting opioids, much of which consists of a prescriber education program, much work is needed on the manufacturing side. The Joint Commission also recently issued guidance on the use of opioids in hospitals.
Consequently, an international research team recently launched an effort to determine “whether everyday painkillers like Celebrex and Aleve could be made safer and more effective through personalized medicine, which involves tailoring treatments to patients based on genetic traits.”
“More than 30 types of such pain medications, known as nonsteroidal anti-inflammatory drugs, or NSAIDs, are on the market, but how well they work varies widely among patients,” reported the Wall Street Journal. NSAIDs work by blocking two enzymes known as Cox-1 and Cox-2. While prescribing labels for all NSAIDs generally warn of both heart and bleeding risks, research suggests there are differences among them.
“Many carry increased risk of such problems as stomach bleeding or heart attacks, and it is hard to predict who is at risk of such side effects and who is likely to benefit from the drugs. The medicines generally are prescribed and used on a trial-and-error basis.”
In an attempt to resolve these issues, “the National Heart Lung and Blood Institute has awarded the University of Pennsylvania an $18 million grant for the first five years of what is expected to be a 10-year project.” Garret FitzGerald, director of the Institute for Translational Medicine & Therapeutics at Penn is heading the project. Dr. FitzGerald, who has enlisted colleagues from institutions including Harvard, Stanford and Duke universities in the U.S. and Cambridge University in the U.K.
The scientists plan a comprehensive look at genetic and other factors that affect how people respond to the medicines in hopes of finding biological signals that could predict efficacy or side effects. The hope is that individual patients could plug their own data into a smartphone app to help decide which medicines to take, at what doses and for how long.” Of course these devices would be heavily regulated by FDA, as they pose significant risks of misuse or adverse events if used improperly, such as overdoses or adverse drug events.
“Personalized medicine already is transforming cancer treatment for some patients whose tumors are fueled by genetic mutations that can be attacked with targeted treatments. But researchers are finding that many diseases involve multiple genetic drivers and a host of other factors that makes predicting the risks and benefits of drugs especially challenging.”
“Naproxen, an over-the-counter pill available in many generic versions as well as under the brand Aleve, marketed by Bayer AG, blocks Cox-1. It is associated with a high risk of gastrointestinal bleeding in some patients, but based on limited studies, it doesn’t appear to increase risk of heart attack, Dr. FitzGerald says. Naproxen also is available through a prescription.”
Another example the article uses is “Celebrex, marketed by Pfizer Inc., a Cox-2 inhibitor. Bleeding risk is generally low, Dr. FitzGerald says, but Celebrex is a cousin of the Cox-2 drug Vioxx, which Merck & Co. withdrew from the market in 2004 because of an increased risk of heart attack and stroke.”
The researchers will test Celebrex and naproxen on five different biological systems: yeast, mammalian cells, mice, zebrafish and humans. They will hunt for patterns among various elements—genetic variants, metabolic processes, even bacteria known as the microbiome that affect human biology—that might be associated with risk or benefit of the medicines. Researchers will then attempt to link any such patterns to risks or benefit in randomized trials involving Celebrex and naproxen as well as other NSAIDs. Researchers hope the process eventually will be applied to other classes of drugs such as cholesterol-lowering statins.
Given industry’s recent support for FDA’s opioid REMS, it will be interesting to see what role they play in supporting a personalized medicine approach to opioids. Certainly, one would expect that companies want to reduce the risk of adverse events or death caused by their drugs, but the research could be extremely expensive and the results may prove more problematic than probative, particularly because even if results are discovered, implementation in everyday practice would take years. Nevertheless, the research represents a new approach to resolving a very real problem our country faces, and the costs of attempting to reduce such problems may eventually be outweighed.