FDA Panel Members: All Arthritis Drugs Suspect
Experts to Vote on Possible Restrictions
Feb. 17, 2005 - All of the arthritis drugs in the family that includes Vioxx 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. 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, and Celebrex 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.
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
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% 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.