Celebrex Passes Cardiac and Gastric Safety Test
The study, conducted by Gurkirpal Singh, MD, and colleagues at Stanford University, was published in the March issue of The American Journal of Medicine and reported by MedPage Today on February 23, 2006.
Additional findings included that Celebrex posed a lower risk of serious gastric effects, while the frequency of cardiovascular thromboembolic events among patients taking Celebrex versus NSAIDs was similar.
Background to the Study
COX-2 inhibitors have been the subject of intense scrutiny in recent years. Merck voluntarily withdrew Vioxx (rofecoxib) from the US market in September 2004, following a report by researchers in a colon-cancer prevention trial that the drug increased thromboembolic events among people who took it daily for 18 months or more.
Shortly thereafter, Pfizer withdrew Bextra (valdecoxib), another COX-2 inhibitor, from the market after reports suggested that it raised risk of heart attack and stroke.
At present, Celebrex is the only COX-2 inhibitor still on the US market.
Although COX-2 inhibitors have been marketed as an alternative to traditional NSAIDs that is gentler on the gastrointestinal (GI) tract, the Celecoxib Long-term Arthritis Safety Study (CLASS), published in 2000, did not conclusively show gastric safety, Dr Singh and colleagues wrote.
Similarly, the Vioxx Gastrointestinal Outcomes Research (VIGOR) trial found that Vioxx (rofecoxib) 50 mg daily was associated with lower GI toxicity than Naprosyn (naproxen) 500 mg twice daily. However, that study has subsequently been criticized as allegedly presenting a misleading picture of the cardiovascular risks associated with Vioxx.
The Current Study
The study by Dr Singh and colleagues -termed the Successive Celecoxib Efficacy and Safety Study-1 (SUCCESS-1) -examined the overall safety, efficacy and tolerability of Celebrex versus NSAIDs Voltaren (diclofenac) and Naprosyn.
SUCCESS-1 included >13,000 people with osteoarthritis in outpatient clinical practices in 39 countries. Patients were randomly assigned to receive Celebrex 100 mg, Celebrex 200 mg, Voltaren 50 mg or Naprosyn 500 mg twice daily, with a follow-up at 12 weeks.
Results showed that Celebrex at both doses alleviate d osteoarthritis symptoms as effectively as the NSAIDs, as assessed by the Patient's Assessment of Pain Visual Analog Scale and other standard assessment tools.
However, compared with the participants taking Celebrex, participants taking NSAIDs were seven times more likely to have ulcer complications, and six times more likely to experience an upper gastrointestinal event.
No significant differences were noted between people taking Celebrex and NSAIDs with regard to the cardiovascular adverse event rate, except for cardiac failure, which was significantly higher among people taking NSAIDs. Although the study found that myocardial infarction risk was reduced among people taking NSAIDs versus Celebrex, this difference was not statistically significant (although the authors noted that the study was not designed to detect such differences).
Finally, a significantly smaller proportion of patients treated with Celebrex had an adverse event compared with those treated with the NSAIDs (37% versus 40%).
"In summary, our study shows that the Cox-2 specific inhibitor celecoxib is as effective as the non-specific NSAIDs naproxen and diclofenac but has significantly fewer serious upper gastrointestinal events," the authors wrote. "The number of cardiovascular thromboembolic events in our study was low, and, although numeric differences were noted, these did not reach statistical significance."
They added, "Because current clinical osteoarthritis treatment guidelines vary in their recommendations regarding the appropriate therapeutic role of Cox-2-specific inhibitors, clinicians should consider a number of factors, including the risk for upper gastrointestinal events, duration of therapy, as well as costs, before deciding upon individual patient treatment."
The study was supported by Pfizer, which makes Celebrex.
Sources:> Celebrex Gets Passing Grades for Gastric and Cardiac Safety, MedPage Today, February 23, 2006. Celecoxib versus naproxen and diclofenac in osteoarthritis patients: SUCCESS-1 study. Singh G et al, The American Journal of Medicine, volume 119, pages 255-266, February 2006.
Posted: March 2006