Drug Firm May Not Call Celebrex Safer, FDA Says
Study Did Not Back Anti-Arthritis Drug Claims
By Susan Okie and Marc Kaufman
Washington Post Staff Writers
Saturday, June 8, 2002; Page A02
The maker of the best-selling arthritis drug Celebrex will not be allowed to claim that its product is safer for the stomach and digestive tract than older, less expensive arthritis medicines, the Food and Drug Administration announced yesterday.
The FDA's decision is a setback for Pharmacia Corp., the drug's manufacturer, which had funded a large study comparing Celebrex to two older drugs in the hope of proving such a safety advantage.
Celebrex and its chief competitor, Vioxx, were the 10th and 13th most frequently prescribed medicines in the United States last year, according to industry data. Although neither drug is better than the older medicines at relieving arthritis pain and inflammation, both have been aggressively marketed as safer because their effects in the body are more narrowly targeted.
Sidney Wolfe, of the Public Citizen Health Research Group, an FDA watchdog, said the latest research undermined Pharmacia's heavily advertised efforts to promote the drug. "The whole hype was that it is safer for the stomach," he said. "If it's not, then why pay five or 10 times more for it? There is no evidence of any benefit in terms of effectiveness, so why would anyone use the drug in the first place?"
In recent weeks, a major pharmacy benefits firm, Express Scripts Inc., charged that both Celebrex and Vioxx are being over-prescribed and recommended that managed-care companies persuade doctors to use the older, less expensive drugs as their first-line arthritis treatments.
According to a spokesman for the CVS drugstore chain, the CVS pharmacy at Dupont Circle charges $96.99 for 30 200-milligram Celebrex pills and $134.99 for 30 50-mg Vioxx pills. Twenty-four pills of over-the-counter 200-mg ibuprofen cost $3.99.
Last April, based on results of a different comparison study, the FDA decided to allow Vioxx's manufacturer, Merck & Co., to claim that its drug has a lower risk of causing ulcers, gastrointestinal bleeding and related digestive-tract complications than the older drugs, known as non-steroidal anti-inflammatory drugs or NSAIDS. Such side effects of NSAIDS are associated with an estimated 100,000 hospitalizations and 16,500 deaths annually in the United States.
Lawrence Goldkind, deputy director of the FDA's division of anti-inflammatory, analgesic and ophthalmic drugs, said the Celebrex study, known as the CLASS study, was specifically trying to determine whether the drug was less harmful to the stomach than other anti-inflammatory medications. He said the researchers used twice as much Celebrex as is usually prescribed.
The company followed 4,000 arthritis sufferers who were treated with Celebrex and 4,000 given ibuprofen or diclofenac, other common anti-inflammatory drugs. The result, Goldkind said, "was that the study did not prove that Celebrex was better for the stomach."
The CLASS study has been controversial because an article containing only the first six months of data, published in 2000 by the Journal of the American Medical Association, concluded that Celebrex caused fewer ulcer complications than the older medicines. At the time, the authors had available 12 months of data which, when analyzed as a whole, showed no significant difference among the drugs.
Goldkind said the study had some complicating issues, including the fact that some patients also took aspirin, which is known to cause some stomach ulcers. He also said the study may have missed some positive effects from the Celebrex treatment. "A failure to show a difference is not the same as showing that things are the same," he said.
Nonetheless, he said the conclusion from the Celebrex study -- and other recently published research into Vioxx, a similar class of anti-inflammatory drug -- was clear. "After studies with 16,000 patients, there was no sign that Cox-2 agents [the class of drugs that includes Celebrex and Vioxx] are overall safer," Goldkind said.
Steven Geis, vice president for clinical research at Pharmacia, said that among Celebrex users in the CLASS study not taking aspirin, the frequency of ulcers that caused symptoms or complications was 0.78 percent -- lower than the 2 percent to 4 percent frequency typically seen among people who take NSAIDS for one year.
Geis added that the CLASS trial also found that heart attacks, strokes and other cardiovascular complications were no more frequent in Celebrex users than in patients on the older drugs. In contrast, a study comparing Vioxx with naproxen, an older NSAID, found a significantly higher rate of serious cardiovascular events in the Vioxx users -- a finding that the FDA ordered Merck to include in the drug's new labeling.
© 2002 The Washington Post Company