Debate Over Celebrex Safety Continues

Two conflicting studies on the pain relief drug Celebrex (search ) are deepening questions over whether the drug’s benefits are worth the risk.

At the same time, one of the nation’s largest health insurers, Kaiser Permanente (search), announced that it would stop covering Bextra because the drug poses an unreasonable safety risk. Both drugs are Cox-2 inhibitors (search ), a class of arthritis drugs that includes Vioxx, which was pulled from the market in the fall amid evidence that it raised the likelihood of heart attack and stroke.

One of the studies, performed in 1999 by Celebrex manufacturer Pfizer Inc., was released for the first time last week on a web site run by the drug industry. It has also raised questions of whether the company withheld critical data about the drug’s potential dangers.

The data, posted to the Internet site of Pharmaceutical Research and Manufacturers of America (PhRMA) last week, has prompted a consumer group to charge that the company kept them from the public for years. Public Citizen (search), a longtime drug industry critic, then wrote to the FDA yesterday saying that the new results bolstered its call to ban both Celebrex and Bextra.

The study was designed to test whether Celebrex can be used to treat Alzheimer’s disease in the elderly. The patients took a high dose of Celebrex (200 mg) twice a day -- twice the typical daily amount. The study showed no Alzheimer’s benefit.

Public Citizen says the data show that patients who took it had a 3.5-times higher risk of problems including chest pain, heart attack, and stroke than patients who took a placebo.

Of 285 elderly patients taking Celebrex, two had heart attacks and five experienced heart failure within one year. None of the 140 patients who took a placebo had heart problems.

Overall, 7.7 percent of patients taking Celebrex and 2.1 percent of those taking placebo had heart problems or a stroke, says Public Citizen.

“This thing showed up and I was astounded that a company would be so stupid as to suppress those data,” says Sidney Wolfe, MD, director of Public Citizen’s Health Research Group, who adds that a colleague made him aware of the data’s appearance on Saturday.

Pfizer officials said yesterday that safety conclusions cannot be drawn from the study because patients taking Celebrex were already at higher risk of heart disease and stroke. The company did not respond to requests for comment Tuesday. Pfizer halted advertising for the drug in December.

The FDA has scheduled hearings for mid-February to look at the safety of the entire class of Cox-2 inhibitors.

Researcher Thinks Celebrex Is OK

In addition to questions over the company’s handling of Celebrex data, the results also add new confusion to concerns over the drug's use by millions of U.S. patients.

Researchers at the National Institutes of Health abruptly halted a colon cancer study in December after data showed an elevated risk of heart attack in patients taking Celebrex.

But another study of nearly 114,000 patients published Monday found that patients taking Celebrex had no greater risk of heart attacks than patients who took traditional anti-inflammatory pain drugs such as ibuprofen.

James Brophy, MD, one of the paper’s researchers, cautions in an interview that only limited conclusions can be drawn from the study, which was a historical look at patients who took Celebrex and was not designed in advance to find heart problems in a controlled way.

But Brophy, who says he agrees with the decision to stop sales of Vioxx (search), does not support calls to pull Celebrex from the market. Several studies have shown no increased heart risk associated with Celebrex, while “a handful” have suggested a potential safety issue, he says.

“You don’t just look at one paper all by itself. You have to look at the totality. My feeling is that there’s really not evidence that it does increase the risk,” says Brophy, a cardiologist and associate professor of medicine at McGill University in Montreal. He points out that the halted NIH study gave patients up to 800 mg of Celebrex per day while the majority of pain patients take 200 mg per day.

Insurer Bans Bextra

Meanwhile, Kaiser Permanente, one of the nation’s largest health insurers, announced Monday that it would no longer cover Bextra (search), citing concerns that the drug’s potential benefits were not worth the potential risks.

"It's a drug that provides a modest degree of pain relief -- no better than Motrin -- and the size of the risk, given the benefit provided, did not seem warranted," Sharon Levine, MD, director of Pharmacy for Kaiser’s Northern California division, told Forbes magazine.

The company says it will continue to pay for Celebrex, saying that it appears less likely to cause heart problems, according to reports. Levine and other Kaiser officials could not be immediately reached for comment.

Curt D. Furberg, MD, who authored a recent study showing an increased risk of heart attack in heart bypass patients taking Bextra, said in an interview last week that data are mounting that the entire Cox-2 inhibitor class may not be worth their possible risks. Like the Kaiser officials, he pointed to data showing that Cox-2 drugs generally offer no more pain relief than available over-the-counter drugs.

“If the drug offers no additional benefit, I don’t know why you should accept the risk,” said Furberg, a professor of pubic health sciences at the Wake Forest University School of Medicine. “I’m saying I will assume they’re unsafe until you prove they’re safe.”

Brophy, while supporting continued use of Celebrex, still urges extreme caution.

He urges patients to use the lowest effective dose of the drug, a position backed by Pfizer, and doctors should “be prudent” about using doses higher than 200 mg per day, he says. “There is a lot of conflicting evidence out there. I’m keeping my eyes and ears open for further research."

By Todd Zwillich, reviewed by Michael W. Smith, MD

SOURCES: Sidney Wolfe, MD, director, Public Citizen Health Research Group. Annals of Internal Medicine, online edition, Jan. 31, 2005. James Brophy, MD, PhD, associate professor of medicine, McGill University, Montreal. Forbes magazine. Curt D. Furberg, MD, professor of public health sciences, Wake Forest University School of Medicine.