Healthy Skepticism Library item: 17905

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Publication type: news

Redfearn S
Journal: Drug Sales Based on 'Seriously Biased' Data
The Washington Post 2002 Jun 4
http://www.washingtonpost.com/wp-dyn/articles/A54319-2002Jun3.html

Full text:

Vioxx and Celebrex are supposed to relieve pain, but their makers are feeling plenty.

In recent months the top-selling arthritis drugs — known as COX-2 inhibitors because they block the COX-2 enzyme, which causes inflammation and thus pain — have been associated with heart problems, kidney damage, aseptic meningitis and slow healing of bone fractures. On June 1, the British Medical Journal (BMJ) ran an editorial asserting that the makers of Celebrex have misled consumers with “over-optimistic” data. And now, perhaps most damaging to the fortunes of the multi-billion-dollar drugs’ makers, a major pharmacy benefits firm is saying the pills are over-prescribed, overpriced and an unnecessary expense for health plans.

Express Scripts Inc., manager of pharmacy benefits for about 50 million insured Americans, recommends that managed care companies persuade doctors to place the costly COX-2 inhibitors at the end of a set of treatment options that begins with cheap, over-the-counter remedies like ibuprofen and aspirin or inexpensive generic prescription drugs like naproxen. Only if these produce side effects or fail to provide relief would doctors write a prescription for a COX-2.

Express Scripts asserts that Vioxx, Celebrex and Bextra (another COX-2 drug) are no more effective than less expensive nonsteroidal anti-inflammatory drugs (NSAIDs) like naproxen and ibuprofen. For each patient who opts for those drugs instead of filling a COX-2 prescription, insurers will save $40 to $50, according to Express Scripts.

The makers of Vioxx and Celebrex assert that their drugs have a distinct advantage over those remedies. COX-2 inhibitors, they say, are the painkiller of choice for people at risk of developing stomach problems from pain remedies and anti-inflammatory drugs. That, say the COX-2 makers, is because other drugs inhibit both the COX-2 and COX-1 enzymes, and the latter help maintain the lining of the gastrointestinal tract.

The BMJ, however, is not so sure COX-2’s have anything over NSAIDs in the stomach-protection department. An editorial in the journal’s June 1 issue asserts that a paper published in September 2000 detailing a long-term arthritis safety study conducted by Celebrex’s makers included misleading results. The BMJ says the report indicated that Celebrex showed a lower incidence of symptomatic ulcers and ulcer complications than NSAIDs. But that was not exactly what the researchers had found. The complete study, pointed out the BMJ, showed that Celebrex caused a similar number of complications as the comparison drugs, and that almost all ulcer complications that occurred during the second half of the trials were seen in people taking Celebrex.

“These results clearly contradict the published conclusions,” said the BMJ, calling the report “seriously biased.” The journal called for an “industry independent” analysis of COX-2 inhibitors to include both published and unpublished data.

Pharmacia Corp., the maker of Celebrex and the less popular Bextra, did not return calls seeking comment on the BMJ’s editorial.

Express Scripts was silent on the effects of COX-2 drugs on the stomach, but it did find that 74 percent of new COX-2 users had no evidence of being at risk for adverse gastrointestinal events. This means the more expensive drugs are being prescribed for people who don’t need them, said Emily Cox, Express Scripts’ manager of outcomes research and lead researcher for the studies. The studies also found that about half of regular COX-2 users also took aspirin for heart health, with half of them taking enough to negate the supposed stomach-soothing effects of the COX-2’s.

In addition, she said, 29 percent of COX-2 users reported taking the drugs for lower back pain, a condition for which the drugs have not been approved. In implementing “step programs,” in which doctors are counseled to start arthritis and pain patients on NSAIDs before moving on to COX-2 drugs, Cox said managed care plans are free to be as aggressive as they want to be. Some HMOs, Cox said, may handle the issue through “profiling” — using software to track what a doctor prescribes. If he or she doles out too much Vioxx or Celebrex, a talking-to may follow.

Merck & Co., the maker of Vioxx, takes issue with Express Scripts’ findings, especially the assertion that almost three-quarters of new COX-2 users are not at risk for stomach problems. Spokesman Gregory Reaves called the report “unfair” and said the company’s findings have shown that one in five people who develop serious upper gastrointestinal reactions to aspirin or ibuprofen are unaware of it and were never deemed “at risk.” These reactions may take the form of undetected bleeding or ulcers in the stomach. Vioxx, Reaves said, has been proven to reduce the incidence of such reactions.

When Celebrex and Vioxx entered the market in 1999, the U.S. Food and Drug Administration (FDA) required that both drugs carry the same warning as ibuprofen and naproxen, one that alerts consumers to possible stomach upset and bleeding. Following a recent study funded by Merck, the FDA allowed Merck to alter Vioxx’s labeling to indicate that, although a risk of stomach problems still exists, it is significantly lower for Vioxx than for NSAIDs.

In responding to Express Scripts’ findings, Pharmacia also pointed to the stomach issue. John Fort, the company’s vice president of global medical affairs, said Celebrex is just as effective as ibuprofen and aspirin, with “an improved safety profile, especially on the gastrointestinal side.”

According to the pharmaceutical consulting firm Scott-Levin, 24.5 million Celebrex prescriptions were filled in the United States in 2001, making it the 10th best-selling drug on the market. Vioxx ranked 13th, with 23.7 million prescriptions filled. Celebrex (jointly marketed by Pharmacia and Pfizer) generated worldwide sales of $3.1 billion last year; Vioxx raked in $2.6 billion.

The two drugs were introduced in 1999 with splashy, expensive TV ad campaigns. But over the last year the buzz has turned sour. Last year, research indicated that Vioxx patients ran four times more risk of heart attack than patients taking aspirin or ibuprofen. Last summer, a study published in the British journal The Lancet associated Vioxx with kidney failure. In March of this year, the FDA reported that five people taking Vioxx had been hospitalized with aseptic meningitis, an inflammation of the membranes covering the brain and spinal cord. And just last week came a report showing that Vioxx and Celebrex slowed the healing of bone fractures in lab animals.

Larry D. Sasich, a pharmacist and research associate with the Wasington-based consumer advocacy organization Public Citizen, recommends traditional anti-inflammatory drugs for arthritis and other pain. His group included COX-2’s on its “worst pills” list in its monthly publication Worst Pills, Best Pills News.

“There’s no evidence that they are any safer on the gastrointestinal tract than drugs that were already on the market,” said Sasich, adding that research performed by drug makers consisted only of visual inspection of the stomach and duodenum, ignoring other parts of the digestive system. Besides, says Sasich, the drugs are overpriced.

Mike DeAngelis, spokesman for CVS drugstores, says the pharmacy at Dupont Circle charges $134.99 for 30 50-mg Vioxx capsules, and $96.99 for 30 200-mg Celebrex pills. The prescription anti-inflammatory generic drug naproxen costs $16.69 for 30 500-mg pills, while 24 pills of over-the-counter 200-mg ibuprofen (Advil) cost $3.99.

Given the pills’ costs, Sasich agrees with Express Scripts’ recent findings. “Individuals and the health care system can save billions of dollars a year just by being informed shoppers,” said Sasich. “So far, they’re not doing it.”