Efficacy of rofecoxib, celecoxib, and acetaminophen in patients with osteoarthritis of the knee. A combined analysis of the VACT studies.

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<or=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.

• Authors: Thomas J Schnitzer, Arthur L Weaver, Adam B Polis, Richard A Petruschke, Gregory P Geba, VACT-1 and VACT-2 (Protocols 106 and 150) Study Groups
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 32 Issue 6 Pg. 1093-105 (Jun 2005) ISSN: 0315-162X [Print] Canada
• PMID: 15940774 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Analgesics, Non-Narcotic
• Cyclooxygenase Inhibitors
• Lactones
• Pyrazoles
• Sulfonamides
• Sulfones
• rofecoxib
• Acetaminophen
• Celecoxib

Topics

• Acetaminophen (therapeutic use)
• Adult
• Analgesics, Non-Narcotic (therapeutic use)
• Celecoxib
• Cyclooxygenase Inhibitors (therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Lactones (therapeutic use)
• Male
• Middle Aged
• Osteoarthritis, Knee (complications, drug therapy, physiopathology)
• Pain (drug therapy, etiology, physiopathology)
• Pain Measurement
• Pyrazoles (therapeutic use)
• Severity of Illness Index
• Sulfonamides (therapeutic use)
• Sulfones (therapeutic use)
• Treatment Outcome