A majority of the patients who were persuaded to use prescription arthritis drugs such as Celebrex and Vioxx would have done just as well on older, cheaper medications and would have avoided the potential risks of heart attack and stroke now linked to those blockbuster drugs, according to a study of how they were marketed and used.
The two COX-2 inhibitors were promoted with aggressive direct-to-consumer advertising campaigns after their approvals in 1998 and 1999, and the researchers conclude that the marketing played a significant role in leading both doctors and patients to overuse them. Merck & Co.'s Vioxx was withdrawn last year after a clinical trial linked it to an increased risk of serious heart attacks and strokes, and Pfizer Inc.'s Celebrex remains under a cloud following similar, though less dramatic, reports of the same problem.
The new study finds that more than 70 percent of patients prescribed the COX-2 drugs in the first three years they were available were at low or very low risk of developing ulcers and gastrointestinal problems -- the conditions that the COX-2 class of drugs was designed to prevent.
"The fast growth of the COX-2 market took place to a significant extent with patients who could have used" nonprescription alternatives, said study author G. Caleb Alexander of the University of Chicago. "In fact, there are clinical reasons to say they should have been using the alternatives."
The COX-2 drugs "were heavily marketed to physicians and the public, and both are known to be susceptible to the impression that newer is better when it comes to medications," he said. "But we know that is not always the case."
A Merck spokeswoman responded that clear policies govern the company's sales and marketing activities, and that "those policies are aimed at ensuring that our product communications are fair and balanced and consistent with FDA labeling." She said the company has training programs in place to make sure that promotions are "consistent with both our standards and our policies."
The new study, published in the journal Archives of Internal Medicine, is the latest to highlight the growing controversy around a class of drugs once seen as offering major improvements in patient care.
The revelations already have driven Vioxx from the market and led to a high-profile Senate hearing where the Food and Drug Administration was sharply criticized for its handling of numerous drug approvals and for its oversight of direct-to-consumer advertising. The agency will hold an unusual three-day meeting next month to assess the safety and benefits of the entire COX-2 class. It also includes Pfizer's drug Bextra, approved by the FDA in 2001.
In anticipation of the meeting, the consumer watchdog group Public Citizen petitioned the FDA yesterday to order all COX-2 drugs off the market.
The new study was initiated to investigate whether the increased cost of the COX-2 drugs produced a greater benefit for patients. Alexander said Vioxx and Celebrex generally cost 10 to 15 times more than nonprescription painkillers such as naproxen and ibuprofen.
But the author's conclusion -- that millions of patients and health plans were paying significantly more money for drugs that gave little or no benefit -- has been overshadowed by the safety concerns.
Those concerns were addressed in another article, released yesterday in the Lancet medical journal, which estimated that Vioxx caused 88,000 to 140,000 additional cases of serious heart disease during its almost five years on the market.
The article, written by FDA whistleblower David Graham, concluded that patients taking Vioxx had a 34 percent greater chance of coronary heart disease than those using other arthritis medications, and that a significant number of people harmed by Vioxx died. He said early clinical trials of Vioxx suggested that manufacturer Merck should have acted earlier to take it off the market.
"In the future, when trials show that a new treatment confers a greater risk of a serious adverse effect than a standard treatment, we must be much more careful about allowing its unrestrained use," Graham, who presented some of his material at the Senate hearing in November, said in a news release.
The Merck spokeswoman said that "any estimate of harm from Vioxx is pure speculation."
The study on advertising analyzed data from two large federal surveys of patient visits to doctors' offices. Researchers looked at usage patterns for the COX-2 drugs and over-the-counter nonsteroidal anti-inflammatory drugs, and compared them with treatment guidelines that put patients into treatment groups based on their risk of gastrointestinal symptoms.
Over the three years of the study, they found, only 2 percent of patients given a COX-2 prescription had a "high risk" of gastrointestinal problems, 25 percent had a "moderate risk," and 73 percent had a "low" or "very low risk."
According to study author Alexander, clinical guidelines generally call for giving COX-2s to patients with high or moderate risk.
Direct-to-consumer advertising for prescription drugs is now a $3.5 billion business, and Vioxx and Celebrex are among the most heavily advertised drugs of all time.
According to the Archives report, Merck spent $161 million on direct-to-consumer advertising in 2000. The advertising tracking firm TNS Media Intelligence/CMR reported that Pfizer spent $87.6 million marketing Celebrex in 2003 and significantly topped that before stopping all advertising for the drug in December. Merck spent $71.7 million for Vioxx ads through the first nine months of the year, after spending $79.2 million in 2003, the tracking firm said.
The United States is one of only two industrialized nations that allow direct-to-consumer pharmaceutical advertising; the other is New Zealand. The rules guiding the advertising were dramatically loosened in 1997, when drug companies were allowed to run some ads that do not disclose side effects but direct patients to Web sites, telephone numbers and their doctors for information on possible problems that are often vaguely described.
Marc Kaufman, Washington Post. January 25, 2005
Copyright © 2005 The Washington Post Company. All rights reserved.