Source: DGNews  |  Posted 9 years ago

By Bruce Sylvester

NEW ORLEANS, LA -- October 29, 2002 -- Retrospective analyses underscore the safety of valdecoxib (Bextra) compared to other drugs used to treat the signs and symptoms of arthritis, researchers report.

The studies were presented here October 28 at the annual meeting of the American College of Rheumatology (ACR).

The first analysis was designed to determine the frequency with which gastrointestinal events occur among osteoarthritis and rheumatoid arthritis patients who were being treated with valdecoxib and non-specific non-steroidal anti-inflammatory drugs (NSAIDs; naproxen, ibuprofen or diclofenac) or placebo.

The researchers used data from 10 clinical trials, each lasting six to 26 weeks.

The investigators looked for the frequency of adverse events in the gastrointestinal system, including stomach ulcer, upset stomach and abdominal pain. They compared the incidence of gastrointestinal events in subjects receiving valdecoxib 10 mg to 80 mg daily, to subjects receiving NSAIDS (recommended dosing) and placebo.

They classified subjects by age group: under 55 years and 55 years or over.

The researchers found that valdecoxib was associated with a significant gastrointestinal safety and tolerability advantage (including a reduced gastric ulcer rate) over standard nonselective NSAID-doses, even with dosages four to eight times greater than approved for osteoarthritis/rheumatoid arthritis (10 mg once daily).

This safety advantage appeared both in subjects under 55 years and in subjects 55 years or over, suggesting that even patients under 55 years are at risk from NSAID-related gastrointestinal toxicity.

Subjects under 55 years had a 27.9 percent (n=1732 valdecoxib 10-80mg/day) versus 33.7 percent (n=833 NSAID) rate for all adverse gastrointestinal events. Subjects 55 and over had a 23.5 percent (n=658 valdecoxib 10-80mg/day) vs. 33.7 percent (n=481 NSAID) rate for all adverse gastrointestinal events.

"Among patients in both age groups, we found that gastrointestinal events occurred at a similar rate in those patients treated with valdecoxib as those treated with placebo, but at a significantly lower rate than that of patients treated with these non-specific NSAIDs," said researcher Glenn Eisen, MD, Associate Professor, Gastroenterology Division, Vanderbilt University Medical Center, Nashville, Tennessee United States. "We concluded that valdecoxib has a superior upper gastrointestinal safety profile, even among patients under 55 years."

In the second retrospective analysis, the researchers investigated the incidence of serious thrombotic adverse events among 3,218 RA patients collected from four randomised controlled trials lasting from six weeks to three months. In all trials, recommended doses as well as higher than recommended doses of valdecoxib were compared with naproxen 500 mg twice daily and with placebo.

"Serious thrombotic events" were defined as heart attack, stroke and other blood clotting events.

The serious thrombotic event percentage rates were: O.4 (placebo, n=529), 0.5 (valdecoxib 10mg, n=601), 0.2 (valdecoxib 20mg, n=513), 0.5 (valdecoxib 40mg, n=627), 0.5 (valdecoxib 80mg, n=204) and naproxen (500mg, n=744).

A patient with more than one thrombotic event (myocardial infarction, cerebrovascular disorder or pulmonary embolism) is counted only once in this overall incidence.

"Our analysis suggests that valdecoxib shows no greater incidence of cardiovascular events than either naproxen or placebo," said lead author Andrew Whelton, MD, adjunct professor of medicine at Johns Hopkins University Medical School in Baltimore, Maryland. "While more data are necessary to confirm this conclusion, our findings suggest that valdecoxib demonstrates a cardiovascular safety profile similar to that of placebo or naproxen."

Dr. Whelton added, "Whether patients were or were not taking aspirin did not significantly impact the incidence of serious adverse events."

The studies were supported by Pharmacia, Inc.