All of the arthritis drugs in the family that includes Vioxx (search) appear to raise the risk of heart attacks and strokes, several members of an FDA panel suggested Wednesday.
Late in a second day of an FDA inquiry into the safety of the drugs, experts appeared to lean heavily toward the conclusion that safety concerns that drove Vioxx from the market in September apply to other similar drugs, known collectively as Cox-2 inhibitors (search). Several suggested that increased heart risks could also apply to several older pain drugs but that the drugs have not been studied extensively enough to be sure.
The committee is scheduled to vote Friday on whether to recommend strengthening safety warnings for Cox-2 inhibitors, restricting their marketing, or possibly banning the use of Celebrex and Bextra, the two remaining Cox-2 drugs on the market.
A conclusion that all Cox-2 drugs suffer from the same safety concerns could also hamper manufacturers in their efforts to push two other Cox-2 drugs to the market if regulators require more safety studies before approving them.
Several experts suggested that evidence was strong to suggest that Vioxx, Bextra (search), and Celebrex (search) all raise the risk of heart attack and stroke. FDA safety officials pointed to the two other unmarketed drugs -- called Arcoxia and Prexige -- with suspicions that they could also carry a risk.
“It does appear to be a class effect that varies by drug and by dose. There’s evidence that establishes that there is an excess risk,” said Thomas Fleming, PhD, a professor of biostatistics at the University of Washington and a member of the panel.
Celebrex in Question
Earlier Thursday, FDA scientist David Graham, MD, presented new evidence showing that Celebrex increased the risk of heart attacks when taken in higher doses. The study at the same time found that Celebrex at lower doses doesn’t influence heart attacks. Graham also presented an analysis suggesting that Vioxx may have caused an estimated 40,000 heart attacks for every 1 million men aged 64-75 who took it.
A second analysis suggested that a handful of older anti-inflammatory drugs, including ibuprofen, indomethacin, and Mobic, could also raise the chance of acute heart attack. Graham did present evidence that all anti-inflammatory drugs raised heart attack risk, but he suggested that regulators should take a closer look at the drugs in an effort to weed out more dangerous drugs.
“I think that there is a signal [of risk] probably for all of these drugs. There may be different mechanisms, but each of these drugs is suspect,” said Steven Abramson, MD, a professor of rheumatology at the New York University School of Medicine and another committee member.
FDA officials also told experts that a one-year study of patients taking Prexige showed that they had a 44 percent greater risk of probable heart attacks, strokes, or death than patients who took the widely used anti-inflammatory drug naproxen. The FDA rejected Novartis’ bid to market the drug in the fall of 2003.
Arcoxia, which is stalled at the FDA because of Cox-2 safety concerns, appeared to show a “trend” toward raised heart and stroke risk, said FDA safety officer Joel Schiffenbauer, MD.
Cox-2 drugs and related anti-inflammatory drugs all fell under suspicion last fall when data emerged showing that Vioxx roughly doubled the risk of heart attacks and strokes in patients who took it. Several other studies have come to light, some showing increased risks with related drugs and others suggesting no safety concerns.
Millions of patients have come to rely on Cox-2 drugs for arthritis pain, and many doctors favor their use because they cause less stomach bleeding than older drugs like ibuprofen.
Patients Want Cox-2 Drugs
FDA regulators convened the three-day inquiry in an effort to find a path toward deciding if a risk of heart attack and stroke applies to a wide group of pain drugs and if so, whether the danger justifies the benefits of Cox-2 and related drugs.
Several arthritis patients and doctors attended an open session urging experts to be cautious before recommending tight restrictions or a ban on Cox-2 use.
“I feel like Celebrex was created for me. Most days I feel better than I did 30 years ago,” said Judy Fogel, an osteoarthritis patient from Ithaca, N.Y.
Betsy Chaney, another Celebrex user, told panelists that she wanted to keep the right to use the drug despite possible heart dangers. “I’m willing, for my quality of life, to take those risks,” she said.
One doctor pointed out that researchers and regulators have known of potential Cox-2 risks since February 2001 when an FDA advisory panel similar to the one meeting this week heard evidence that the drugs can raise the risk of dangerous heart problems.
“The question before us is did American doctors prescribe $7 billion worth of Vioxx after Merck and the FDA knew” of the risks, said John Abramson, a family physician from Harvard University.
By Todd Zwillich, reviewed by Michael W. Smith, MD
SOURCES: Thomas Fleming, PhD, professor of biostatistics, University of Washington; member, FDA advisory panel. Steven Abramson, MD, professor of rheumatology, New York University School of Medicine; FDA panel member. Joel Schiffenbauer, MD, FDA safety officer. Judy Fogel, osteoarthritis patient, Ithaca, N.Y. Betsy Chaney, arthritis patient. John Abramson, family physician, Harvard University.
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