Clinical Trials of Coxibs in Rheumatoid Arthritis (RA)

Clinical Trials of Coxibs in RA

Celecoxib

Celecoxib is approved for the treatment of RA in the United States. Efficacy of celecoxib was established in a dose-ranging study and two phase III trials. In a 4-week dose-ranging study, 330 patients with RA were treated with celecoxib 40 mg, 200 mg, or 400 mg twice daily, or placebo. Mean improvements with celecoxib 200 mg or 400 mg twice daily were significantly superior to placebo.(8)

A 12-week phase III trial compared the efficacy of celecoxib 100 mg, 200 mg, or 400 mg twice daily with naproxen 500 mg twice daily or placebo in 1,149 patients with RA. Treatment with celecoxib 200 mg or 400 mg twice daily produced mean improvements comparable to those with naproxen and significantly superior to outcomes with placebo (P <.05).(12)

In a second phase III study, 655 patients with RA were treated for 24 weeks with celecoxib 200 mg twice daily or diclofenac SR 75 mg twice daily. Mean improvements with celecoxib were comparable to outcomes with diclofenac.(31)

The efficacy of coxibs in the treatment of rheumatoid arthritis

—Celecoxib and valdecoxib are the only coxibs currently approved for the treatment of RA in the United States.

—Celecoxib 200 mg twice daily or 400 mg twice daily is as effective as naproxen 500 mg twice daily in the treatment of RA.

—Celecoxib 200 mg twice daily is as effective as diclofenac SR 75 mg twice daily in the treatment of RA.

—Rofecoxib 25 mg once daily or 50 mg once daily is as effective as naproxen 500 mg twice daily in the treatment of RA.

—Valdecoxib 10 mg once daily is as effective as naproxen 500 mg twice daily in the treatment of RA.

—Etoricoxib 90 mg and 120 mg once daily is significantly more effective than placebo in the treatment of RA.

—Etoricoxib 90 mg once daily is as or more effective than naproxen 500 mg twice daily in the treatment of RA.

Rofecoxib

The efficacy of rofecoxib in the treatment of RA has been studied, and a claim for use in RA is pending. In an 8-week dose-ranging trial, 658 patients with RA were treated with rofecoxib 5 mg, 25 mg, or 50 mg once daily, or placebo. Mean improvements with rofecoxib 25 mg or 50 mg once daily were significantly superior to the responses to placebo (P <.001).(15)

Two phase III studies were conducted in approximately 2,000 patients with RA. In one study, participants were treated with rofecoxib 25 mg or 50 mg once daily, naproxen 500 mg twice daily, or placebo for 12 weeks.(49) In the other study, patients were treated with rofecoxib 12.5 mg or 25 mg once daily, naproxen 500 mg twice daily, or placebo for 12 weeks.(50) In all outcome measures, rofecoxib at doses of 25 and 50 mg once daily was comparable to naproxen and significantly superior to placebo (P <.05).

Valdecoxib

The recent approval of valdecoxib also includes its use for the treatment of RA at a dosage of 10 mg once daily. At this dosage, a 12-week study found the efficacy of this agent superior to placebo and similar to that of naproxen (500 mg BID) but with improved GI tolerability compared with naproxen.(51)

Etoricoxib

Etoricoxib is under investigation also for the treatment of RA. An 8-week dose-ranging study was conducted in 581 patients with RA. Patients were treated with etoricoxib 10 mg, 60 mg, 90 mg, or 120 mg once daily, or placebo. Etoricoxib 90 mg and 120 mg once daily were significantly superior to placebo in all outcome measures (P <.05).(52) Maximal improvement was noted with etoricoxib 90 mg once daily.

A 12-week study compared the efficacy of etoricoxib 90 mg once daily with naproxen 500 mg twice daily or placebo in patients with RA. Mean improvements in all primary and key secondary measures were significantly better with etoricoxib compared with naproxen or placebo (P <.05).(53)

Schnitzer TJ, Hochberg MC. COX-2-selective inhibitors in the treatment of arthritis. Cleve Clin J Med 2002;69:SI20-30.