Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
A Fixed-Dose Combination of Naproxen and Esomeprazole Magnesium (VIMOVO) Has Comparable Efficacy and Tolerability to Celecoxib in Patients with Osteoarthritis (OA) of the Knee: Results from Two Randomized, Controlled Trials.
Sostek1, Mark B., Svensson2, Ola, Hwang1, Clara, Fort3, John G., Cryer5, Byron, Hochberg4, Marc C.
It is recommended that patients (pts) at risk for serious NSAID-associated upper gastrointestinal (UGI) toxicity should receive a COX-2 selective inhibitor, or a nonselective NSAID plus gastroprotection. The efficacy and tolerability of a fixed-dose combination (FDC) of enteric-coated naproxen 500mg and immediate-release esomeprazole magnesium 20mg was compared with celecoxib 200mg in 2 identical, non-inferiority studies in pts with OA.
Two double-blind, double-dummy, placebo-controlled, multicenter Phase 3 studies (307/309) enrolled pts aged >=50 years with symptomatic OA of the knee. Following an OA flare, pts were randomized 2:2:1 to receive FDC naproxen/esomeprazole BID, celecoxib 200 mg QD, or placebo for 12 weeks. The primary endpoints were mean change from baseline to Week 12 in WOMAC pain, WOMAC function, and Patient Global Assessment (PGA) of OA using a visual analog scale (VAS, 0100mm); each endpoint had prespecified non-inferiority margin of 10mm between active treatments. Tolerability endpoints included the modified Severity Of Dyspepsia Assessment (mSODA), heartburn severity, and predefined NSAID-associated UGI adverse events (AEs).
Study 307: 619 pts were randomized, 614 were treated, and 521 completed; Study 309: 615 pts were randomized, 610 were treated, and 489 completed. Baseline demographics were similar between treatment groups in both studies; mean age was 62 years and >60% were women. Improvements in WOMAC pain and function, and PGA were seen with naproxen/esomeprazole and celecoxib in both studies. Naproxen/esomeprazole was non-inferior to celecoxib for each primary endpoint; upper/lower limits of 95% CI of treatment differences were <5mm (table). Both active treatments showed significantly greater efficacy vs placebo in Study 307 (p<0.05), while only naproxen/esomeprazole was significantly superior to placebo in Study 309 (p<0.05). The incidence of UGI AEs was 17.3% in Study 307 and 20.3% in Study 309, and was similar between treatment groups. UGI AEs reported by >=3% of pts were dyspepsia, nausea, and upper abdominal pain. In Study 307, 1.2%, 1.6%, and 2.4% of pts discontinued due to UGI AEs in the naproxen/esomeprazole, celecoxib, and placebo groups, respectively; in Study 309, 0.8%, 3.7%, and 2.5% withdrew, respectively. Improvements in mSODA scores were similar across treatment groups in both studies, with no significant differences between active treatments (table). Pts treated with naproxen/esomeprazole had significantly more heartburn-free days vs those treated with celecoxib (95% CIs: Study 307: 2.1, 12.7; Study 309: 2.5, 13.4) and placebo (95% CIs: Study 307: 6.4, 19.2; Study 309: 1.1, 14.4).
With non-inferior efficacy and comparable UGI tolerability to celecoxib, naproxen/esomeprazole may offer an effective and well-tolerated treatment option for pts with knee OA at risk for serious UGI AEs.
To cite this abstract, please use the following information:
Sostek, Mark B., Svensson, Ola, Hwang, Clara, Fort, John G., Cryer, Byron, Hochberg, Marc C.; A Fixed-Dose Combination of Naproxen and Esomeprazole Magnesium (VIMOVO) Has Comparable Efficacy and Tolerability to Celecoxib in Patients with Osteoarthritis (OA) of the Knee: Results from Two Randomized, Controlled Trials. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :937