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Efficacy of Rofecoxib, Celecoxib, and Acetaminophen in Patients with Osteoarthritis of the Knee.
A Combined Analysis of the VACT Studies
THOMAS J. SCHNITZER, ARTHUR L. WEAVER, ADAM B. POLIS, RICHARD A. PETRUSCHKE, and GREGORY P. GEBA, for the VACT-1 and VACT-2 (Protocols 106 and 150) Study Groups
ABSTRACT.
Objective. To compare efficacy among 1578 patients with osteoarthritis randomized to take acetaminophen 4000 mg (n = 269), celecoxib 200 mg (n = 523), rofecoxib 12.5 mg (n = 259), or rofecoxib 25 mg (n = 527) in a double blind trial [Vioxx, Acetaminophen, Celecoxib Trial (VACT2)]. Results were also pooled with the similarly designed VACT1 trial. Methods. Patients evaluated over Days 1 to 6 and 6 weeks with Patient Global Assessment of Response to Therapy (PGART) and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. Results. For VACT2, median time to good or excellent PGART response was 6, 5, 4, and 3 days for acetaminophen, celecoxib, rofecoxib 12.5 mg, and rofecoxib 25 mg (COX-2 inhibitors vs acetaminophen, p ≤ 0.035; rofecoxib 25 mg vs celecoxib, p = 0.01). WOMAC response over the first 6 days was greater (p < 0.05) with both rofecoxib doses than acetaminophen and celecoxib. At Week 6, all COX-2 inhibitors provided significantly greater efficacy than acetaminophen. Good or excellent PGART was numerically, but not significantly, greater with rofecoxib 25 mg (55.4%) than celecoxib (50.6%) at Week 6; a significant difference was seen at Weeks 2 (6.9, p = 0.022) and 4 (6.7, p = 0.027) and over 6 weeks with analysis of all 5 PGART categories of response (p = 0.035). Rofecoxib 25 mg provided greater response (p < 0.05) than celecoxib on WOMAC subscales. Pooled analysis of VACT1/VACT2 demonstrated greater PGART (p = 0.023) with rofecoxib 25 mg (56.1%) than celecoxib (49.8%) at 6 weeks and greater response to all other PGART and WOMAC endpoints, and confirmed superiority of COX-2 inhibitors to acetaminophen. Overall, tolerability of the study medications was generally good and similar. There was no significant difference between treatment groups in the percentage of patients who experienced a clinical adverse experience (AE). The incidence of discontinuations due to an AE was significantly lower with celecoxib (2.5%) compared to rofecoxib 25 mg (6.3%, p = 0.004) or acetaminophen (7.8%, p < 0.001), and did not differ significantly from rofecoxib 12.5 mg (4.6%). Discontinuation rates due to edema and hypertension related AE were similar among all COX-2 inhibitors. Conclusion. Rofecoxib and celecoxib provided superior efficacy to acetaminophen. There was a more rapid and greater response with rofecoxib 25 mg than celecoxib 200 mg. Rofecoxib 12.5 mg demonstrated greater efficacy than celecoxib 200 mg over the first 6 days, and was similar over 6 weeks. All study medications were generally well tolerated. (J Rheumatol 2005;32:1093-105) Key Indexing Terms:
ROFECOXIB
From Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Nebraska Medical Center, Omaha, Nebraska; and Merck & Co., Inc., West Point, Pennsylvania, USA. Funding for the VACT studies provided by Merck & Co., Inc., West Point, PA, USA. T.J. Schnitzer, MD, PhD, Professor of Medicine, Assistant Dean for Clinical Research, Division of Rheumatology, Department of Internal Medicine, Northwestern University Feinberg School of Medicine; A.L. Weaver, MD, Professor of Medicine, Division of Rheumatology, Department of Internal Medicine, University of Nebraska Medical Center; A.B. Polis, MA; R.A. Petruschke, PharmD; G.P. Geba, MD, MPH, Merck & Co., Inc. Address reprint requests to Dr. T.J. Schnitzer, Northwestern University Feinberg School of Medicine, 710 N. Lake Shore Drive, Room 1020, Chicago, IL 60611. E-mail: tjs@northwestern.edu Accepted for publication January 17, 2005. |