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.
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.
University of Texas Southwestern Medical Center, Dallas, USA. Byron.Cryer@UTSouthwestern.edu
Byron L
BL
Cryer
Mark B
MB
Sostek
John G
JG
Fort
Ola
O
Svensson
Clara
C
Hwang
Marc C
MC
Hochberg
D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004338:Drug Combinations; D004415:Dyspepsia / Q000139:chemically induced; D064098:Esomeprazole / Q000008:administration & dosage*; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects*; D006356:Heartburn / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000008:administration & dosage* / Q000009:adverse effects; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use; D013608:Tablets, Enteric-Coated; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D052246:Cyclooxygenase 2 Inhibitors; D004338:Drug Combinations; D011720:Pyrazoles; D013449:Sulfonamides; D013608:Tablets, Enteric-Coated; D009288:Naproxen; D000068579:Celecoxib; D064098:Esomeprazole