Drs. Paul Moore and Elliott Hersh should be complimented on their review of celecoxib and rofecoxib for including the basic science, as currently understood, of the cyclooxygenase chain and the promise of selective COX-2 inhibition ("Celecoxib and Rofecoxib: The Role of COX-2 Inhibitors in Dental Practice," April JADA).
For their conclusions and the text on the JADA cover highlighting the report, "Two new NSAIDs limit adverse reactions," Drs. Moore and Hersh relied heavily on the two outcomes trials: CLASS (Celecoxib Long-term Arthritis Safety Study)1 and VIGOR (Vioxx Gastrointestinal Outcome Research trial).2
In terms of general safety, these large trials reported celecoxib and rofecoxib to be as safe as selected traditional non-steroidal anti-inflammatory drugs, or NSAIDs, in the treatment and setting of osteoarthritis and rheumatoid arthritis.
However, we feel Drs. Moore and Hersh failed to include an unambiguous and undebatable finding from both studies: neither CLASS nor VIGOR reported general tolerability of the COX-2–specific NSAIDs to have a clinically significant advantage over traditional NSAIDs.
Specifically, the CLASS authors reported that 18.4 percent of patients randomized to celecoxib withdrew because of adverse effects vs. 20.6 percent of patients randomized to ibuprofen or diclofenac. In the VIGOR trial, 16.4 percent of patients randomized to rofecoxib withdrew because of adverse events vs. 16.1 percent of patients randomized to naproxen.
With interest in gastrointestinal, or GI, toxicity, Drs. Moore and Hersh note reports of life-threatening and fatal ulcer complications in association with celecoxib and rofecoxib. In preparation for the public Food and Drug Administration Arthritis Advisory Committee meeting on the regulatory implications of the CLASS and VIGOR trials (Feb. 7 and 8, 2001), we summarized 73 cases of fatal GI bleeding, obstruction, perforation or stenosis associated with both acute and chronic use of celecoxib or rofecoxib.3–5
Most of these patients were at high risk of developing a GI complication. It is unknown if these cases represent the background rate or high-risk individuals whose clinicians elected to employ celecoxib or rofecoxib in lieu of nonpharmacologic modalities or possibly acetaminophen.
Pending studies of patients at high risk of developing a GI complication, it is unknown if the modest clinical improvements in GI events reported in clinical trials for celecoxib and rofecoxib—including CLASS and VIGOR, with mean ages of 60 and 59 years, respectively—translate to high-risk patients.
As implied but not stated in the article, high-risk patients are addressed in current U.S. labeling for all NSAIDs, including celecoxib and rofecoxib. Specifically, these product labels recommend extreme caution in the use of these agents in patients with a history of peptic ulcer disease or GI bleeding, and special care in treating elderly or debilitated patients.
The views expressed are those of the authors and do not necessarily represent those of, nor imply endorsement from, the Food and Drug Administration or the U.S. government.
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