As reported by the Danbury News-Times, February 16, 2005.

FDA Hearing to Determine Arthritis Drugs' Safety

By Robert Miller

For the past 4 months, doctors, patients, drug companies and the medical establishment have tried to determine if some of the top prescription arthritis drugs are safe.

Beginning today, the U.S. Food and Drug Administration will hold a three-day hearing into these drugs, called COX-2 inhibitors.

The FDA hopes to learn whether the drugs need stronger warnings on their labels or whether they should be on the market at all.

By Friday, doctors hope to have an indication about who should use the drugs and when.

"I think it will help to take us out of the limbo," said Dr. Richard Roseff, a Danbury rheumatologist.

COX-2 drugs are non-steroidal, anti-inflammatory drugs, or NSAIDs. Doctors prescribe them because these drugs control pain without causing gastric ulcers – a serious side effect that kills about 16,000 a year.

The controversy began in October, when the pharmaceutical giant Merck pulled its COX-2 drug Vioxx off the market after research showed high doses increased the risk of heart attacks.

Subsequent studies showed the most popular COX-2 drug – Celebrex, made by Pfizer– also increased the risk of heart attacks.

A third study showed high doses of Pfizer's Bextra increased the risk of heart attack in patients who had undergone coronary bypass surgery.

Dr. Kenneth Miller, a rheumatologist with Arthritis Associates of Danbury, New Milford and Carmel, N.Y., said these studies looked at short-term effects of high dosages of the drugs.

"But the question then became whether people taking the drugs at smaller doses over the long-term are at the same risk," Miller said.

The studies also intensified criticism of the FDA, with doctors and public health specialists accusing the agency of listening too much to drug companies selling their products, and failing to do long-term studies to show if the drugs it approves are safe.

The FDA advisory panel will look at these studies and others, as well as listen to speakers debate. By Friday, it will make recommendations about the drugs' future.

The New England Journal of Medicine, which was to publish the studies in March, released them Tuesday.

Journal editor Dr. Jeffrey Drazen said early release of the studies would allow physicians – including those attending the FDA conference – to have the complete text and research.

"It's like the difference between seeing the preview of the movie and seeing the entire movie," Drazen said. "We think having all the information out in its complete form will be valuable."

Drazen's accompanying editorial questions if "it is reasonable to ask whether the use of the drugs can now be justified," now that the FDA knows the risks.

If the FDA had monitoring mechanisms to follow new drugs for several years, he said "substantial morbidity and perhaps a substantial number of deaths could have been prevented.''

But Dr. William White – a professor of medicine and cardiologist at the University of Connecticut School of Medicine said no drugs are without risk.

"The questions we have to ask are 'What are the risks? How bad are they? And can a patient tolerate the risks in exchange for the benefits?' " White said. "If you tell a patient this drug will reduce your pain without gastric bleeding, but with a slightly increased risk of having a heart attack, I think the patient might choose to take the drug."

White said it's important to note at lower doses, there's no evidence that COX-2 drugs cause more cardiac events than other arthritis drugs on the market.

But, White said there is evidence COX-2 drugs reduce the risk of developing colon polyps, which lead to colon cancer. If a patient has a history of colon polyps, but not a heart disease, COX-2 drugs might be valuable.

Finally, Miller of Arthritis Associates said several published studies on Celebrex do not show it increases risk of heart attacks.

"This may be what we call a Type 2 error," he said of one study that indicates Celebrex causes problems. "That follows the idea that if you do enough studies, you'll eventually have one that shows different results."

Roseff and Miller have patients who depend on these drugs.

"The day doesn't go by that I don't have a patient tell me how much he benefited from Vioxx,'' Roseff said.

The doctors expect the FDA, rather than pulling all the COX-2 drugs off the market, will insist drug companies provide patients with detailed warnings of their risks.

"I hope the FDA won't take them off the market," Miller said. "If it does, that will set us back about five years.''