FDA advisers to assess safety of arthritis drugs

By RANDOLPH E. SCHMID

Associated Press Writer

WASHINGTON - Vioxx and other pain-relieving drugs have given many people with chronic pain the chance to resume normal lives. But an increase in heart attacks among users of the popular arthritis drug led the manufacturer to pull it from the market and has cast a shadow over similar medications.

Advisers to the Food and Drug Administration meet this week to see if a balance can be found between benefits from these kinds of prescription drugs and the dangers they may pose.

Over three days beginning Wednesday, two advisory groups will hear from regulators, pharmaceutical companies, researchers, doctors and the public in an effort to understand what went wrong that led to Vioxx being withdrawn and raised doubts about others - and what needs to be done now.

Merck & Co.'s Vioxx and two similar drugs - Pfizer Inc.'s Celebrex and Bextra, both of which remain on the market - are among a new class called Cox-2 inhibitors used widely to treat arthritis and other chronic conditions.

These drugs, which target the Cox-2 enzyme involved in inflammation, avoided the stomach and intestinal problems that can occur with other medications that affect both Cox-1 and Cox-2 enzymes. The Cox-1 enzyme helps the stomach maintain its protective coating.

Clinical trials found few serious problems with the new drugs. But there was an increase in heart attacks and strokes among patients taking part in a long-term trial to gauge the effectiveness of Vioxx in preventing cancer.

As a result, Merck halted the study and pulled Vioxx from the market on Sept. 30.

In a memo to the two FDA advisory committees, the agency's Center for Drug Evaluation and Research noted that many consumers and scientists have questioned whether any Cox-2 drug should be allowed to remain on sale.

"What is your view? Is there a patient population for whom the risk is warranted, given the known potential for benefit?" the agency asked the arthritis and the drug safety and risk management committees.

It is not clear how the drugs may cause heart problems; that is one more question the committees will consider.

One suggestion is that because Vioxx seems to increase blood pressure, heart trouble could result.

A second possibility is that Vioxx directly affects endothelial cells, which line the heart and blood vessels. The Cox-2 enzyme affects those cells and some researchers believe blocking it may have led to the heart problems.

The withdrawal of Vioxx also raised questions about the safety of Celebrex and Bextra.

A 1999 study of Alzheimer's patients taking Celebrex indicated that the patients had four times the risk of heart problems. Pfizer contends that definitive conclusions cannot be drawn from that study.

In December, a different study linked Celebrex to increased cardiovascular problems. Pfizer's president of worldwide development, Dr. Joseph Feczko, said the results in that study were not consistent with a "large body of data" the company had collected.

In November a preliminary study discussed at the American Heart Association's annual meeting indicated Bextra more than doubled the risk of heart attack and stroke among heart disease patients.

Pfizer said those findings were "unsubstantiated conclusions" that had not been subjected to independent scientific review. But the company advised regulators that it will add to the Bextra packaging a warning of a potentially fatal skin reaction linked to the drug.

The FDA has received a request from the consumer group Public Citizen to order Celebrex and Bextra from the market, which the agency is reviewing.

While awaiting findings of the advisory committees, the FDA has urged physicians and patients to use caution with any painkiller.

Dr. John K. Jenkins, the FDA's director of new drugs, said even such popular over-the-counter products as Aleve, ibuprofen and aspirin should not be used longer than 10 days without consulting a doctor.

Naproxen, a popular painkiller sold as Aleve and Naprosyn, has been implicated in heart problems in a National Institutes of Health study.

"This is a rapidly evolving area," Jenkins said.

Painkillers such as aspirin can carry a serious risk of stomach and intestinal bleeding, Jenkins said, and doctors must balance this with the potential heart risk of some of the other drugs.

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