A fixed-dose combination of naproxen and esomeprazole magnesium has comparable upper gastrointestinal tolerability to celecoxib in patients with osteoarthritis of the knee: Results from two randomized, parallel-group, placebo-controlled trials

Abstract

Background. Non-steroidal anti-inflammatory drugs are associated with poor upper gastrointestinal (UGI) tolerability and increased ulcer risk, but patient adherence to gastroprotective co-therapy is frequently inadequate. A fixed-dose combination of enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg was evaluated: efficacy is reported by Hochberg et al. (Curr Med Res Opin 2011;27:1243–53); tolerability findings are reported here.

Patients and methods. In two 12-week double-blind, placebo-controlled, multicenter, phase III studies (PN400-307 and PN400-309), patients aged ≥ 50 years with symptomatic knee osteoarthritis randomly (2:2:1) received naproxen/esomeprazole magnesium BID, celecoxib 200 mg QD, or placebo. Tolerability end-points included: modified Severity of Dyspepsia Assessment (mSODA); heartburn severity; and UGI adverse events (AEs).

Results. Overall, 619 (PN400-307) and 615 (PN400-309) patients were randomized; mSODA scores improved (baseline to week 12) in each group, with no significant treatment differences between naproxen/esomeprazole magnesium and celecoxib (95% CIs: PN400-307: –0.4, 1.9; PN400-309: –1.8, 0.6). Naproxen/esomeprazole magnesium-treated patients reported significantly more heartburn-free days versus celecoxib (95% CIs: PN400-307: 2.1, 12.7; PN400-309: 2.5, 13.4). UGI AE incidence (PN400-307: 17.3%; PN400-309: 20.3%) was similar between treatment groups. UGI AEs resulted in few discontinuations (< 4%, either study).

Conclusions. Naproxen/esomeprazole magnesium has comparable UGI tolerability to celecoxib in patients with osteoarthritis.

Key words::

• Celecoxib
• drug therapy combination
• dyspepsia
• esomeprazole
• heartburn
• mSODA
• naproxen
• proton pump inhibitors
• tolerability
• upper gastrointestinal tract

Declaration of interest: Dr Byron L. Cryer is a consultant to AstraZeneca, Horizon Therapeutics, NiCox Inc., PLx Pharma, Pfizer Inc., and POZEN Inc.

Dr Marc C. Hochberg is a consultant to and/or receives speaker fees from AstraZeneca, Bayer Health Care LLC, Bioiberica SA, CombinatoRx, Eli Lilly, Endo Pharmaceuticals, GlaxoSmithKline, Merck, Merck Serono International, NicOx SA, Novartis, Pfizer, POZEN Inc., and sanofi-aventis, and research grants from the National Institutes of Health.

Dr John G. Fort is an employee of POZEN Inc. with stock ownership. Dr Mark B. Sostek, Dr Ola Svensson, and Ms Clara Hwang are employees of AstraZeneca.

Acknowledgment

These studies were sponsored and conducted by POZEN Inc. Statistical analysis was conducted under the direction of Cemal Unal, formerly of POZEN Inc., and additional statistical support was provided by Ying Zhang (POZEN Inc.). We thank Lynsey Stevenson, of Complete Medical Communications, who provided medical writing support funded by AstraZeneca.