Osteoarthritis (OA) is often treated with nonsteroidal anti-inflammatory
drugs (NSAIDs), acetaminophen, or specific inhibitors of cyclooxygenase 2
To assess the relative therapeutic efficacy of rofecoxib, celecoxib,
and acetaminophen in adults with OA.
Design and Setting
Randomized, parallel-group, double-blind trial, conducted from June
1999 to February 2000, in 29 clinical centers in the United States.
Three hundred eighty-two patients aged at least 40 years who had OA
of the knee that was previously treated with NSAIDs or acetaminophen.
Patients were randomly assigned to receive rofecoxib, 12.5 mg/d (n =
96); rofecoxib, 25 mg/d (n = 95); celecoxib, 200 mg/d (n = 97); or acetaminophen,
4000 mg/d (n = 94) for 6 weeks.
Main Outcome Measures
Assessments over days 1 to 6 and over 6 weeks included pain on walking,
night pain, pain at rest, and morning stiffness as measured on a Western Ontario
McMaster Universities Osteoarthritis Index (100-mm visual analog scale [VAS])
and global response to therapy compared among 4 treatment groups.
79% of patients completed the study. More patients treated with acetaminophen
discontinued early due to lack of efficacy than patients treated with COX-2
inhibitors (31% vs 18%-19%). Efficacy assessed in the first 6 days of therapy
showed greatest response to rofecoxib, 25 mg/d, followed by rofecoxib, 12.5
mg/d, celecoxib, and acetaminophen, respectively, in terms of relief of pain
on walking (−32.2, − 29.0, − 26.4, and −20.6 mm change
on the VAS; P≤.04 for all others vs acetaminophen; P = .05 for 25-mg rofecoxib vs celecoxib), rest pain (−21.8, −
18.6, − 15.5, and − 12.5 mm; P≤.02
for either dose of rofecoxib vs acetaminophen and P
= .02 for rofecoxib, 25 mg/d, vs celecoxib), night pain (−25.2, −
22.0, − 18.7, and − 18.8 mm; P = .04
for rofecoxib, 25 mg/d, vs both acetaminophen and celecoxib), and morning
stiffness (−30.4, − 28.4, − 25.7, and − 20.9 mm; P≤.02 for either dose of rofecoxib vs acetaminophen).
Over 6 weeks, rofecoxib, 25 mg/d, provided greatest response for night pain
(P<.002 vs celecoxib and P
= .006 vs acetaminophen and P = .02 vs rofecoxib,
12.5 mg/d), composite pain subscale (P≤.03 vs
all other treatments), stiffness subscale (P≤.04
vs celecoxib and acetaminophen), and physical function subscale (P = .001 vs acetaminophen). Global responses over 6 weeks showed a
similar pattern (good or excellent response at week 6: 60%, 56%, 46%, and
39%, respectively; P≤.03 for rofecoxib, 25 mg/d,
vs celecoxib and acetaminophen; P = .02 for rofecoxib,
12.5 mg/d, vs acetaminophen). All treatments were generally safe and well
Rofecoxib, 25 mg/d, provided efficacy advantages over acetaminophen,
4000 mg/d, celecoxib, 200 mg/d, and rofecoxib, 12.5 mg, for symptomatic knee