May 30, 2002 -- Sales of the arthritis drug Celebrex topped $3 billion last year, mainly because it is believed to be a safer choice than traditional anti-inflammatory drugs. But its safety is now being called into question with the revelation that a key study showing its superiority omitted critical data.
The published report of the Celebrex Long Term Arthritis Safety Study (CLASS), sponsored by the drug's manufacturer, concluded that people taking Celebrex for six months had lower rates of stomach and intestinal ulcers than those taking two older arthritis drugs - diclofenac and ibuprofen. But the study actually lasted for a year, and the summary ignored later data showing no safety advantage for the newer drug.
"Within a year of the publication of this trial, sales of Celebrex increased by almost a billion dollars," arthritis researcher Peter Juni, MD, of Switzerland's University of Berne tells WebMD. "The economic incentives to manipulate trial data are huge. We are not talking about thousands of dollars here, or even millions. We are talking about billions."
In a newly published editorial, Juni argues that the CLASS authors essentially got away with manipulating their data, even though the incident was reported in The Washington Post and several medical publications.
"[The study] may still be relied on by many doctors without reference to these flaws," he wrote in the June 1 issue of the British Medical Journal. "In our experience most still believe the findings published originally."
Celebrex was the first drug of its kind -- called Cox-2 inhibitors -- to be approved. Vioxx followed shortly thereafter and Bextra hit the market in late 2001. These drugs are widely believed to cause fewer stomach ulcers and stomach bleeding than traditional arthritis treatments. In his editorial, Juni calls for an independent review of all studies evaluating the safety of the Cox-2 drugs.
While highly critical of the CLASS authors, arthritis researcher Chris Hawkey tells WebMD that the findings still suggest a safety advantage for Celebrex. In a separate BMJ editorial, Hawkey noted that the failure of the study could have had more to do with the design of the trial than with inadequacies in the drug itself.
He notes that a large and widely reported trial that he was involved in showed an unequivocal advantage for Vioxx over traditional arthritis drugs in terms of safety. Hawkey is a professor in gastroenterology at University Hospital Nottingham, England.
"When you take all of the available data into account, it is pretty clear that for gut safety, these two drugs are better than earlier drugs," he tells WebMD. "But they are probably the same with regard to other side effects."
In fact, in April 2002, the FDA officially approved Vioxx as being safer on the stomach than traditional anti-inflammatory drugs. Currently, the makers of the other Cox-2 inhibitors are not able to say this.
Like traditional anti-inflammatory drugs, the Cox-2 drugs have been associated with an elevated risk of swelling and high blood pressure. This is particularly problematic because both arthritis and high blood pressure are common among the elderly. But Hawkey says new drugs are being developed that may offer arthritis treatment without these side effects.
"These drugs offer promise, but they are still in very early trials," Hawkey says. "But they may one day offer a better treatment option for older patients with arthritis and high blood pressure."
This decision to use an anti-inflammatory drug is obviously a complicated one -- and one that needs to be made between you and your doctor. Research continues and, we hope, should be able to settle the Cox-2 inhibitor safety question once and for all.