Etoricoxib and Naproxen May Have Long-Term Efficacy and Tolerability for OA Treatment

August 6, 2007 — Etoricoxib (60 mg once daily) has similar efficacy as naproxen (500 mg twice daily) in controlling osteoarthritis (OA) and both are well tolerated, according to a combined analysis of 2 long-term randomized controlled trials published in the July issue of Annals of the Rheumatic Diseases.
"Etoricoxib is a COX [cyclo-oxygenase]-2 selective inhibitor that has demonstrated efficacy in patients with OA," write J.Y. Reginster, MD, PhD, from the Polycliniques Universitaires L. Brull in Liege, Belgium, and colleagues. "Recent studies have suggested that COX-2 selective inhibitors are associated with an increased risk of thrombotic cardiovascular (CV) events in comparison with placebo. Data are also available that suggest that traditional NSAIDs [nonsteroidal anti-inflammatory drugs] are associated with increased CV risk."
At 80 clinical centers in 19 countries, 997 patients with hip or knee OA entered 2 double-blind, parallel-group trials, each with a 12-week part 1, a 40-week part 2, and an 86-week extension. Patients randomized to receive placebo during part 1 received etoricoxib or naproxen (1:1 ratio) during part 2 and the extension, whereas patients randomized to receive etoricoxib or naproxen during part 1 continued to receive the same treatment throughout part 2 and the extension.
Main efficacy outcomes were patient global assessment of disease status, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire pain subscale and physical function subscale using a 100-mm visual analog scale. Graphical analysis charted efficacy during the 138-week study period. Safety analysis included adverse event documentation, physical examinations, and laboratory testing.
Of 997 patients who entered part 1, 615 (62%) patients completed parts 1 and 2, and 463 (46%) patients entered the 86-week extensions. The entire 138 weeks of treatment were completed by 161 patients in the etoricoxib group and by 152 in the naproxen group. Throughout the 138 weeks of treatment, etoricoxib and naproxen were similarly effective.
The WOMAC pain assessments were 67 mm in both groups at baseline, 28 mm for etoricoxib and 29 mm for naproxen at 1 year, and 34 and 33 mm, respectively, at 138 weeks. For other efficacy outcomes, findings were similar to those reflected by the WOMAC pain assessments.
Although both treatments were well tolerated overall and a similar proportion of patients in each group had an adverse event during the entire study period, the specific types of adverse events in each treatment group were somewhat different. The etoricoxib group had fewer gastrointestinal adverse events than did the naproxen group.
In both groups, hypertension was among the most frequent adverse events, but the incidence of hypertension was greater with etoricoxib than with naproxen. Discontinuations of use of study drugs because of hypertension were infrequent and similar in both groups. Other renovascular adverse events, including lower extremity edema and congestive heart failure, occurred with similar frequency in both groups. A greater proportion of patients had a thrombotic CV event in the etoricoxib group than in the naproxen group, but the incidence of thrombotic CV events was low in both groups.
Study limitations include not being specifically powered to evaluate CV risk.
"Both etoricoxib and naproxen demonstrated long-term clinical efficacy for the treatment of OA," the authors write. "Although these studies were not powered to evaluate the relative risk of GI [gastrointestinal] or CV events, the safety data from these studies suggest that etoricoxib has a more favourable GI safety and tolerability profile than naproxen, whereas naproxen is associated with a numerically lower incidence of thrombotic CV events."
Ann Rheum Dis. 2007;66:945-951.