Dec. 23, 2002 -- On New Year's Eve 1998, arthritis patients and the doctors who treat them had good reason to celebrate: The FDA approved a new kind of painkiller, Celebrex, that promised to be as effective as traditional non-steroidal anti-inflammatory drugs, but without causing serious stomach ulcers associated with long-term NSAID use.
Now four years later, a new study suggests Celebrex is no more effective in preventing a recurrent bleeding ulcer in arthritis patients than treatment with a traditional NSAID plus Prilosec, the popular heartburn medication proved to help prevent these stomach ulcers.
Prilosec is a proton pump inhibitor, which is given to arthritis patients who have a history of a bleeding ulcer because of the high risks of rebleeding with NSAID treatment.
Nearly 5% of the study patients who took Celebrex suffered recurrent bleeding -- a potentially life-threatening condition -- compared with 6% who took a traditional NSAID plus Prilosec.
"Pandora's box has been opened," says David Y. Graham, MD, chief of gastroenterology at Baylor College of Medicine. "We have developed a false sense of security that needs to be re-examined."
This new study, by a team of highly respected Hong Kong researchers, is published in the Dec. 26 issue of the New England Journal of Medicine. It's the latest finding to somewhat tarnish the once golden reputation of COX-2 inhibitors, a class of drugs that includes Celebrex and Vioxx - the most widely prescribed medications for the one in five Americans with arthritis. Four months ago, a study in the Journal of the American Medical Association indicated that COX-2 inhibitors (specifically Vioxx) doubled the risk of heart attack.
However, Graham, who wrote an accompanying editorial to the new Celebrex finding, says that most arthritis patients will still fare better with it than with daily doses of NSAIDs such as ibuprofen and aspirin.
"For the average consumer, COX-2 inhibitors are still much safer than traditional NSAIDs, as it pertains to gastrointestinal problems," he tells WebMD. "But it does appear as though COX-2 inhibitors are not completely safe, that they may be less safe than originally thought, and that Vioxx may be even less safe than Celebrex."
This finding is significant because one in four patients who routinely take NSAIDs for arthritis relief develop some signs of these stomach, or peptic, ulcers. Each year, about 4% of these patients develop full-blown bleeding ulcers. "Once you have an ulcer that bleeds, they are extremely difficult to heal and recur almost the day you start taking NSAIDS again," says Graham.
Besides NSAID use, the other primary cause of peptic ulcers is infection by Helicobacter pylori (H. pylori), a bacterium that afflicts about one in five Americans younger than age 40 and as many as half of those older than 60. Both NSAIDs and H. pylori weaken the protective mucous coating of the stomach and duodenum, the upper portion of the intestines, allowing acid to eat into this lining, causing an ulcer.
Because of the high rate of peptic ulcers associated with NSAID use, arthritis patients were often left with a dilemma: Manage the arthritis pain and risk serious stomach complications or manage the ulcer and live with the pain. Then along came Celebrex -- and months later, Vioxx, which promised freedom from both problems.
But the new study found that "rates of recurrent ulcer bleeding were substantial" in both the 144 participants who took Celebrex and the 143 who received diclofenac (sold as Voltaren or Cataflam) plus Prilosec, which previous studies indicate helps protect against these ulcers. All 287 study participants had tested negative for H. pylori infection.
"The prediction has been that COX-2 inhibitors would not be associated with this recurrence," Graham tells WebMD. "But now, it's clear that we need to do more to find out what we can do for these high-risk patients. The question is, what?"