Gastrointestinal tolerability and effectiveness of rofecoxib versus naproxen in the treatment of osteoarthritis: a randomized, controlled trial.
BACKGROUND
Gastrointestinal (GI) toxicity mediated by dual cyclooxygenase (COX)-1 and COX-2 inhibition of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious alterations of mucosal integrity or, more commonly, intolerable GI symptoms that may necessitate discontinuation of therapy. Unlike NSAIDs, rofecoxib targets only the COX-2 isoform.


OBJECTIVE
To assess the tolerability of rofecoxib compared with naproxen for treatment of osteoarthritis.


METHODS
Randomized, controlled trial.


METHODS
600 office and clinical research sites.


METHODS
5557 patients (mean age, 63 years) with a baseline diagnosis of osteoarthritis of the knee, hip, hand, or spine.


METHODS
Rofecoxib, 25 mg/d, or naproxen, 500 mg twice daily. Use of routine medications, including aspirin, was permitted.


METHODS
Discontinuation due to GI adverse events (primary end point) and use of concomitant medication to treat GI symptoms (secondary end point). Efficacy was determined by patient-reported global assessment of disease status and the Australian/Canadian Osteoarthritis Hand Index, as well as discontinuations due to lack of efficacy. Patients were evaluated at baseline and at weeks 6 and 12.


RESULTS
Rates of cumulative discontinuation due to GI adverse events were statistically significantly lower in the rofecoxib group than in the naproxen group (5.9% vs. 8.1%; relative risk, 0.74 [95% CI, 0.60 to 0.92]; P = 0.005), as were rates of cumulative use of medication to treat GI symptoms (9.1% vs. 11.2%; relative risk, 0.79 [CI, 0.66 to 0.96]; P = 0.014]). Subgroup analysis of patients who used low-dose aspirin (13%) and those who previously discontinued using arthritis medication because of GI symptoms (15%) demonstrated a relative risk similar to the overall sample for discontinuation due to GI adverse events (relative risk, 0.56 [CI, 0.31 to 1.01] and 0.53 [CI, 0.34 to 0.84], respectively). No statistically significant difference was observed between treatments for efficacy in treating osteoarthritis or for occurrence of other adverse events.


CONCLUSIONS
In patients with osteoarthritis treated for 12 weeks, rofecoxib, 25 mg/d, was as effective as naproxen, 500 mg twice daily, but had statistically significantly superior GI tolerability and led to less use of concomitant GI medications. Benefits of rofecoxib in subgroup analyses were consistent with findings in the overall sample.
Lisse
Jeffrey R
JR
University of Arizona, Tuscon, USA.
Perlman
Monica
M
Johansson
Gunnar
G
Shoemaker
James R
JR
Schechtman
Joy
J
Skalky
Carol S
CS
Dixon
Mary E
ME
Polis
Adam B
AB
Mollen
Arthur J
AJ
Geba
Gregory P
GP
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000150:complications; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006801:Humans; D006973:Hypertension / Q000150:complications; D007783:Lactones / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects* / Q000627:therapeutic use; D010003:Osteoarthritis / Q000150:complications / Q000188:drug therapy*; D011446:Prospective Studies; D013450:Sulfones
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D009288:Naproxen; D001241:Aspirin