Fixed-dose combination of enteric-coated naproxen and immediate-release esomeprazole has comparable efficacy to celecoxib for knee osteoarthritis: two randomized trials.
Author(s): Hochberg MC, Fort JG, Svensson O, Hwang C, Sostek M
Affiliation(s): Division of Rheumatology & Clinical Immunology,University of Maryland School of Medicine, Baltimore, MD 21201, USA. email@example.com
Publication date & source: 2011-06, Curr Med Res Opin., 27(6):1243-53. Epub 2011 Apr 28.
Publication type: Clinical Trial; Clinical Trial, Phase III; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
OBJECTIVE: To demonstrate that a fixed-dose combination of enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg has comparable efficacy to celecoxib for knee osteoarthritis. RESEARCH DESIGN AND METHODS: Two randomized, double-blind, parallel-group, placebo-controlled, multicenter phase III studies (PN400-307 and PN400-309) enrolled patients aged >/=50 years with symptomatic knee osteoarthritis. Following an osteoarthritis flare, patients received naproxen/esomeprazole magnesium twice daily, celecoxib 200 mg once daily, or placebo for 12 weeks. CLINICAL TRIAL REGISTRATION: NCT00664560 and NCT00665431. MAIN OUTCOME MEASURES: Three co-primary efficacy endpoints were mean change from baseline to week 12 in Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain and function subscales, and Patient Global Assessment of osteoarthritis using a visual analog scale (PGA-VAS). RESULTS: In Study 307, 619 patients were randomized and 614 treated. In Study 309, 615 patients were randomized and 610 treated. Both naproxen/esomeprazole magnesium and celecoxib were associated with improvements (least squares mean change from baseline to week 12) in WOMAC pain (Study 307: -42.0 and -41.8, respectively; Study 309: -44.2 and -42.9, respectively), WOMAC function (Study 307: -36.4 and -36.3, respectively; Study 309: -38.9 and -36.8, respectively), and PGA-VAS (Study 307: 21.2 and 21.6, respectively; Study 309: 29.0 and 25.6, respectively). A prespecified non-inferiority margin of 10 mm between naproxen/esomeprazole magnesium and celecoxib was satisfied for each co-primary endpoint at week 12 in both studies. Significant improvements were observed with naproxen/esomeprazole magnesium versus placebo in both studies (p < 0.05). Celecoxib was significantly different from placebo in Study 307 (p < 0.05); however, the improvements were not significant in Study 309. Acetaminophen use and patient expectation of receiving active treatment (80% probability) may have contributed to a high placebo response observed. CONCLUSIONS: Naproxen/esomeprazole magnesium has comparable efficacy to celecoxib for the management of pain associated with osteoarthritis of the knee over 12 weeks.