First COX-2 Inhibitor Approved for OA and RA

January 4, 1999

FDA has approved celecoxib (Celebrex) for relief of the signs and symptoms of osteoarthritis (OA) and adult rheumatoid arthritis (RA). First in a new group of drugs that specifically inhibit the cyclooxygenase-2 (COX-2) enzyme, it will be comarketed by G.D. Searle & Co. and Pfizer Inc.

While the COX-2 inhibitors have been widely touted as safer alternatives to NSAIDs, FDA is requiring the same gastrointestinal warning label on Celebrex as it does on NSAIDs. The move brings into question whether celecoxib is sufficiently specific for COX-2 and provides a boost for Merck, whose rofecoxib (Vioxx) NDA is under review at FDA. (At the October 1998 annual meeting of the American College of Gastroenterology, researchers reported that rofecoxib, an investigational drug for pain and arthritis, was no different than placebo in its adverse effects on the gastrointestinal mucosa.). Also of concern with these new drugs is that the COX-2 enzyme occurs in kidney and brain, so side effects in these organs will not be lessened by COX-2 inhibitors. Long-term safety of each COX-2 inhibitor is currently being assessed in studies sponsored by the companies.

Clinical trials of celecoxib included more than 13,000 patients and healthy volunteers in 23 countries. It was as effective as prescription-strength naproxen in treating arthritis pain and inflammation. The most common gastrointestinal side effects of celecoxib were dyspepsia, diarrhea, and abdominal pain, which resulted in drug discontinuation in less than 1% of subjects. Patients who have a known allergic reaction to celecoxib, sulfonamides, aspirin, or NSAIDs should not use celecoxib.

Recommended doses of celecoxib are 200 mg daily for OA and 100-200 mg daily for RA.