ANALYSIS OF THE ONSET OF EFFICACY WITH ROFECOXIB, CELECOXIB, AND ACETAMINOPHEN IN OSTEOARTHRITIS: THE VACT-2 TRIAL

Background: The cyclooxygenase (COX)-2 selective inhibitors rofecoxib (ROF) and celecoxib (CEL) have demonstrated a rapid onset of efficacy in pain models.Objectives: We compared the onset of efficacy over the first 6 days of therapy of the selective inhibitors of COX-2, ROF and CEL, and acetaminophen (ACET) as a secondary endpoint in a randomized, double-blind trial of osteoarthritis (OA) patients, VACT-2.Methods: 1578 patients with OA of the knee were enrolled. Patients received treatment with ROF 12.5 mg (n=259), ROF 25 mg (n=527), CEL 200 mg (n=523), or ACET 4000 mg (n=269) daily for 6 weeks. Time-to-event analysis was performed using Wilcoxons rank test to evaluate time patients first reported Good or Excellent Patient Global Assessment of Response to Therapy (PGART) during Days 1 to 6. Response during the onset period was also analyzed comparing time-weighted mean changes from baseline of Western Ontario and McMaster Universities (WOMAC) OA Index (visual analog scale [VAS], 0 no pain to 100 extreme pain) for Pain Walking on a Flat Surface, Night Pain, Rest Pain, and Morning Stiffness.Results: Demographics were similar across treatment groups. The majority of patients were Caucasian (88%), female (67%), median age of 62 years. Median time to a Good or Excellent PGART response was Day 3, 4, 5, and 6 for ROF 25 mg, ROF 12.5 mg, CEL, and ACET, respectively. Time to a Good or Excellent PGART response was significantly quicker (p=0.01) for ROF 25 mg compared to CEL. All coxibs had significantly quicker time to response than ACET (p-values < or =0.035). For the four WOMAC endpoints, both ROF 12.5 mg and ROF 25 mg had significantly greater reductions compared to CEL (p-values<0.05) and ACET (p-values<0.01).Conclusion: ROF 25 mg provided significantly quicker onset of OA efficacy compared to CEL 200 mg based on PGART. All coxibs provided quicker onset than ACET 4000 mg based on PGART. Response during the onset period with both ROF doses was superior to response with CEL or ACET based on WOMAC assessments.Citation: , volume , supplement , year 2003, page Session: Osteoarthritis – Clinical aspects and treatment