The National Cancer Institute suspended a large study of Celebrex Friday after a safety review found the popular arthritis drug more than tripled heart attacks, strokes and heart-related deaths in patients on high doses.
The development deals another blow to the once-promising class of non-steroidal anti-inflammatory drugs called COX-2 inhibitors, prompting consumer advocates, including Public Citizen, to demand Celebrex be taken off the market. It also raised troubling questions about the Food and Drug Administration’s ability to keep dangerous drugs off the market.
A lengthy letter in next week’s New England Journal of Medicine argues against taking Pfizer’s Bextra, another COX-2 inhibitor, “except in extraordinary circumstances.” The letter points to clinical trials that found a tripling of serious heart outcomes in patients who had undergone bypass surgery. The FDA recently added a black box warning to the drug, calling attention to its risks.
In late September, Merck & Co. yanked Vioxx, another COX-2 inhibitor, off the market after cancer prevention studies found it doubled the risk of heart attack and stroke.
“Physicians should consider this evolving information in evaluating the risks and benefits of Celebrex,” said Dr. Lester Crawford, FDA’s acting commissioner. “The FDA advises evaluating an alternative therapy.” If a doctor determines the drug is appropriate, it should be prescribed and taken at the “lowest effective dose,” he said.
The new findings grew out of a clinical trial testing Celebrex for prevention of polyps and colon cancer. Among patients taking 400 mg a day of Celebrex, 2.2 percent suffered a heart attack, stroke or death, compared with 0.9 percent of those on a placebo. But among those taking 800 mg a day, 3.4 percent suffered adverse cardiovascular outcomes.
Some 2,000 patients participated in the trial. Those taking Celebrex were on the drug an average of 33 months, National Cancer Institute officials said.
Dozens of other clinical trials testing Celebrex for prevention of cancer and Alzheimer’s will continue, officials said.
Pfizer Inc., which makes Celebrex, said it had no plans to withdraw the drug from the market.
Officials of Pfizer said a separate colon polyp and cancer prevention study the company is running did not find any increase in cardiovascular risk. That study has participants on 400 mg a day of Celebrex.
C. Michael Stein, one of the authors of the letter about Bextra, said the NCI findings were surprising. “Most of the data so far for Celebrex had been relatively reassuring as to its cardiovascular safety I think we will move away from using the drugs as casually as we have done in the past.”
The spate of bad news does not bode well for drugs of that class in development, researchers said.
“This is huge,” said Dr. Judith Beizer, a professor at St. John’s University College of Pharmacy and Allied Health. “The implications for drugs in the pipelines are that they’ll be looked at very, very closely before they’re approved.”
The recommended dose is 100 mg to 200 mg daily to treat osteoarthritis and 200 mg to 400 mg to treat rheumatoid arthritis. Celebrex is also approved at doses up to 800 mg a day for familial adenomatous polyposis, a rare colon cancer predisposition syndrome, Pfizer said.