title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. tjs@northwestern.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schnitzer
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Weaver
authors.forename: Adam B
authors.initials: AB
authors.lastname: Polis
authors.forename: Richard A
authors.initials: RA
authors.lastname: Petruschke
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Geba
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D010147:Pain Measurement; D011720:Pyrazoles / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000627:therapeutic use*; D013450:Sulfones / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018712:Analgesics, Non-Narcotic; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D000082:Acetaminophen; D000068579:Celecoxib