Costly arthritis drugs aren't living up to hype

Medical Matters

Medicine & Science

August 02, 2004|By Judy Foreman | Judy Foreman,SPECIAL TO THE SUN

Seduced by hundreds of millions of dollars in advertising, Americans spend $6 billion a year for the arthritis painkillers Vioxx and Celebrex, said to be as good as over-the-counter drugs - and easier on the stomach.

But the two have not lived up to their hype, according to published research and interviews with arthritis doctors and drug specialists. Vioxx, which may be better for the stomach, appears to have a far worse side effect than over-the-counter drugs: an increased risk of heart attacks.

For reasons doctors don't yet understand, Celebrex does not seem to be linked to heart problems, but there's conflicting evidence whether it has any benefit for the stomach. There's also no evidence that these drugs are any better at fighting pain than comparable doses of older medications such as ibuprofen - though they cost six times as much.

At CVS, a month's supply of ibuprofen at the doses people with arthritis normally take costs $17.55; a comparable supply of Celebrex costs $107.99, and Vioxx, $110.99. Depending on co-payments, the consumer may end up paying the same or even more for over-the-counter drugs, though, because insurance doesn't defray costs for nonprescription medications.

Vioxx and Celebrex, like their lesser-known cousins Bextra and Mobic, are in a relatively new class of drugs called Cox-2 inhibitors.

Despite the saturation advertising aimed at the 22 million Americans who suffer from arthritis, "there is no proof that these Cox-2 drugs are better for arthritis pain than traditional ibuprofen, and there is also no proof, except for a certain subset of patients, that these drugs are safer," said Dr. Neil Minkoff, medical director of pharmacy at Harvard Pilgrim Health Care, which insures 800,000 people in Massachusetts, New Hampshire and Maine.

Some insurers insist that doctors get prior approval before writing prescriptions for them.

Back in the late 1990s, when the hype over Vioxx and Celebrex began, the excitement seemed well-founded. Researchers had long known that prostaglandins, natural chemicals that are made in cells under the direction of enzymes called cyclooxygenases, were the root cause of pain and inflammation.

But it turned out there were actually two types of cyclooxygenases, dubbed Cox-1 and Cox-2. Cox-1 releases "good" prostaglandins that protect the stomach. Cox-2 releases "bad" prostaglandins that further drive inflammation. The new drugs were hailed for their ability to block only Cox-2 and leave the good prostaglandins intact, something that traditional over-the-counter anti-inflammatory drugs such as ibuprofen could not do.

Early appeal

Eager to get the pain-killing benefits without stomach-killing side effects such as bleeding ulcers, doctors and patients flocked to the new drugs to help dampen the pain of arthritis, as well as migraines, acute pain and menstrual cramps. Then the bad news began trickling out.

The Cox-2 inhibitors actually "don't eliminate gastrointestinal side effects, they just reduce them somewhat, and even that is more problematic than first thought," said Dr. Jerry Avorn, chief of pharmacoepidemiology and pharmacoeconomics at Brigham and Women's Hospital, and author of the coming book Powerful Medicines on the subject.

Evolving results

In September 2000, a study on 8,000 patients showed that people taking Celebrex over a six-month period had fewer ulcer complications than those taking nonprescription drugs.

When a later analysis by the U.S. Food and Drug Administration looked at 12 months' worth of data, this apparent advantage disappeared.

In November 2000, a study called VIGOR showed that 50 milligrams a day of Vioxx - a relatively high dose - reduced the risk of serious stomach problems by half, compared with prescription-strength naproxen (Aleve). But the study, published in the New England Journal of Medicine, also showed that the risk of heart attack was two to four times higher for patients on Vioxx. Since then, the data have been conflicting, with most - but not all - studies showing a link between Vioxx and heart disease.

This spring, researchers from Brigham and Women's Hospital, writing in the journal Circulation, concluded that compared with high doses of Celebrex, high doses of Vioxx were linked to a 70 percent increase in heart attack risk in the first 90 days.

Dr. Lee Simon, a rheumatologist at Beth Israel Deaconess Medical Center, said that people should realize that it's not wise to take 50-milligram doses of Vioxx for more than a week, but 12.5 mg and 25 mg a day are safer.

Consumers, shareholders and regulators, not surprisingly, have not been thrilled about these studies.

FDA warning

In 2001, the U.S. Food and Drug Administration issued a "warning letter" about Merck & Co. Inc.'s promotional activities for Vioxx, which the agency said was minimizing the potential heart attack link. It also issued a warning letter to Pfizer about misleading promotion of Celebrex, particularly its potentially harmful interactions with Coumadin, a common blood thinner.

Pfizer would not comment on the warning letter or discuss possible litigation over Celebrex, but Merck is clearly on the defensive.

Merck officials say they have corrected the problem with heart risk data from three studies on its package labeling, said company spokeswoman Mary Elizabeth Blake.

But in New Orleans, the Kahn Gauthier Law Group is leading a shareholders' proposed class action suit against Merck alleging that the company artificially inflated its stock prices based upon false and misleading statements about the safety of Vioxx. In New Jersey and California, lawyers are handling more than 200 personal injury lawsuits claiming that Merck failed to warn consumers about Vioxx' potential risks.

So where does this leave us? Use over-the-counter medications if they work for you. If they don't, or if they cause stomach problems, talk to your doctor.

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