title: Fixed-dose combination of enteric-coated naproxen and immediate-release esomeprazole has comparable efficacy to celecoxib for knee osteoarthritis: two randomized trials.
abstract: 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.
  
  
  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.
  
  
  BACKGROUND
  NCT00664560 and NCT00665431.
  
  
  METHODS
  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.
authors.affiliation: Division of Rheumatology & Clinical Immunology,University of Maryland School of Medicine, Baltimore, MD 21201, USA. mhochber@medicine.umaryland.edu
authors.forename: Marc C
authors.initials: MC
authors.lastname: Hochberg
authors.forename: John G
authors.initials: JG
authors.lastname: Fort
authors.forename: Ola
authors.initials: O
authors.lastname: Svensson
authors.forename: Clara
authors.initials: C
authors.lastname: Hwang
authors.forename: Mark
authors.initials: M
authors.lastname: Sostek
mesh_terms: D000068579:Celecoxib; D004311:Double-Blind Method; D004338:Drug Combinations; D064098:Esomeprazole / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D009288:Naproxen / Q000008:administration & dosage / Q000627:therapeutic use*; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D010919:Placebos; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D010919:Placebos; D011720:Pyrazoles; D013449:Sulfonamides; D009288:Naproxen; D000068579:Celecoxib; D064098:Esomeprazole