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Stubborn FDA harms arthritis sufferers

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Stubborn FDA harms arthritis sufferers

Arnett op ed in The Providence Journal

Helvetia, W.Va. – The Food And Drug Administration’s (FDA) safety alert for the popular diabetes drug Avandia has gotten headlines recently, but its handling of an arthritis drug a few weeks ago may be far more ominous when it comes to public health. On April 27 the agency rejected Merck’s application for its new arthritis drug, Arcoxia. This has been widely characterized as a wise move to protect patients, but it does nothing of the sort. In fact, it denies patients a badly needed new option that could benefit millions. And it sets a terrible precedent for our future. <?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

Especially hard hit are arthritis sufferers. An estimated 46 million Americans suffer from chronic arthritis, and this number will increase by 46 percent by 2030 as our population ages. The disease worsens over time and causes severe pain, joint stiffness and disability. A class of drugs known as non-steroidal anti-inflammatory drugs has traditionally relieved the pain—aspirin and Motrin being the best known. These drugs, however, have dangerous gastrointestinal side effects such as abdominal bleeding that, if severe, can cause death.

In 1999 the FDA approved Vioxx, Bextra and Celebrex. These were the first members of a new class of NSAIDs that provided similar pain relief but caused only half as many side effects. They became so popular that, by 2004, their combined yearly sales was more than $5 billion.

But in 2004, studies appeared that associated Vioxx with a small increased risk of heart attacks and other cardiovascular side effects, and Merck withdrew the drug from the market. An FDA advisory panel recommended that Vioxx be reinstated and that Bextra be left on the market. Unfortunately, in spite of this, Merck declined to reintroduce Vioxx, and in April 2005, the FDA asked Pfizer to withdraw Bextra. Celebrex was left as the only such drug on the market.

In December 2003, Merck submitted a new drug application for another drug in this category known as Arcoxia, which already was used in more than 60 countries around the world. In November 2006, the company released results from a four-year clinical trial of Arcoxia, the largest and longest arthritis study ever undertaken, and the only one with cardiovascular safety as its endpoint. It showed that in older patients Arcoxia had the same rate of cardiovascular complications as did Voltaren, which is the most widely prescribed NSAID in the world. But Arcoxia reduced the number of gastrointestinal side effects.

Millions of patients likely would choose to use the drug since, for them, its benefits greatly outweigh its risks. Nonetheless, FDA turned Arcoxia down in late April, evidently because the drug was shown to be only as good as Voltaren, not better. It was derisively termed to be a “me-too” drug, undeserving of approval in a drug category that was now viewed to have too many side effects for comfort.

But the treatment of chronic pain is far too complex to be hemmed by such a rigid approach. Treating pain is idiosyncratic—not every patient responds in the same way, and some patients may respond in very different ways. These variations in response are not well understood; some of them may be due to genetic differences.

Such variations can often be hidden in studies. For example, even though certain sub-groups of patients in any large study may experience greater pain relief, this may not be apparent from the average response rate found for the group as a whole. Instead, it will go unnoticed.

That’s why, for effective drugs that have a small risk of side effects, the more choices available the better. “Me-too” drugs such as Arcoxia that have benefits and side effects similar to older drugs already marketed give physicians badly needed new choices. Patients also benefit because the availability of another similar drug on the market should lead to lower prices. In short, the more “me-too” drugs we have, the better.

Physicians often need to try several drugs of the same type before finding the one that best helps a particular patient. In my own practice of internal medicine I treat many patients who need another drug for control of their chronic pain. If Arcoxia had been approved, I would have been able to offer it to them. None of my patients who used Vioxx (after several other NSAIDs failed to help them) have since been able to find another drug as effective. They would welcome Vioxx if it were made available again.

That’s me speaking as an internist. Rheumatologists and orthopedic surgeons experience an even greater need for more drug choices. A recent survey of orthopedic surgeons released by the Competitive Enterprise Institute, for example, found that 80 percent would like to see Vioxx again made available for their patients.

The new category of drugs represented by Vioxx, Bextra, Celebrex and Arcoxia has huge promise. But right now the only drug in that class that’s available in the <?xml:namespace prefix = st1 ns = "urn:schemas-microsoft-com:office:smarttags" />United States is Celebrex. With the FDA apparently raising the bar even higher for the approval of new “me-too” drugs, that category may remain near empty for a long time to come. And that, rather than Vioxx or Arcoxia, is the real threat, both to my patients and to you.