Journal: Drug Sales Based on 'Seriously Biased' Data

Celebrex, Vioxx Cited For Problems, Claims

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.