 |
|
|
 |
Gastrointestinal Side Effects of Etoricoxib in Patients with Osteoarthritis: Results of the Etoricoxib versus Diclofenac Sodium Gastrointestinal Tolerability and Effectiveness (EDGE) Trial
HERBERT S.B. BARAF, CARLOS FUENTEALBA, MARIA GREENWALD, JAN BRZEZICKI, KATHERINE O'BRIEN, BETH SOFFER, ADAM POLIS, STEVEN BIRD, AMARJOT KAUR, and SEAN P. CURTIS, for the EDGE Study Group ABSTRACT. Objective. To compare the gastrointestinal (GI) tolerability, safety, and efficacy of etoricoxib and diclofenac in patients with osteoarthritis (OA). Methods. In total, 7111 patients (mean age 64 yrs) diagnosed with OA were enrolled in a randomized, double-blind trial. Patients received etoricoxib 90 mg qd (n = 3593) or diclofenac sodium 50 mg tid (n = 3518). Gastroprotective agents and low-dose aspirin were prescribed per treatment guidelines. The primary endpoint was the cumulative rate of discontinuations due to clinical and laboratory GI adverse experiences (AE). General safety was assessed, including adjudication of thrombotic cardiovascular (CV) safety data. Efficacy was evaluated using the least-square (LS) mean change from baseline patient global assessment of disease status (PGADS; 0–4 point scale). Results. Mean (SD, maximum) duration of treatment was 9.3 (4.4, 16.5) and 8.9 (4.5, 16.6) months in the etoricoxib and diclofenac groups, respectively. The cumulative discontinuation rate due to GI AE was significantly lower with etoricoxib than diclofenac [9.4 vs 19.2 events per 100 patient-years (PY), respectively; hazard ratio (HR) 0.50 (95% CI 0.43, 0.58; p < 0.001). Rates of thrombotic CV events were similar with etoricoxib and diclofenac [1.25 vs 1.15 events per 100 PY, respectively; HR 1.07 (95% CI 0.65, 1.74)]. The incidence of patients who discontinued due to hypertension-related AE was significantly higher with etoricoxib compared to diclofenac (2.3% vs 0.7%; p < 0.001), although few AE were severe (3 etoricoxib, 1 diclofenac). Etoricoxib and diclofenac treatment resulted in similar improvements in PGADS from baseline of –0.78 (95% CI –0.80, –0.75) and –0.75 (95% CI –0.77, –0.72), respectively. Conclusion. Treatment with etoricoxib 90 mg was associated with significantly better GI tolerability compared to diclofenac in this population of patients with OA. Etoricoxib 90 mg, a dose 50% higher than indicated for OA, resulted in more discontinuations due to hypertension-related AE. (J Rheumatol 2007;34:408–20) Key Indexing Terms:
ETORICOXIB From the Center for Rheumatology and Bone Research, Wheaton, Maryland, USA; Hospital San Borja Arriarán, Santiago, Chile; Desert Medical Advances, Palm Desert, California, USA; Oddzial Reumatologii – Wojewodzki Szpital Zespolony, Elblag, Poland; and Merck & Co., Inc., West Point, Pennsylvania, and Rahway, New Jersey, USA. Supported by Merck & Co., Inc., Whitehouse Station, NJ, USA. Clinical study protocol registered at http://www.clinicaltrials.gov/ct/show/ NCT00092703. H.S.B. Baraf serves as a consultant for Merck & Co. and Savient Pharmaceuticals. He has received research grant support from Merck & Co., Pfizer, Amgen, Centocor, Abbott Laboratories, TAP Pharmaceutical Products, GlaxoSmithKline, Sanofi-Aventis, and Savient Pharmaceuticals. He has served as a speaker for Merck & Co., Pfizer, Amgen, Centocor, Abbott, and TAP Pharmaceutical Products. C. Fuentealba has received research support from and served as a speaker for Merck & Co. M. Greenwald has received research support from Abbott Laboratories, Allelix, Amgen, Sanofi-Aventis, Biogen Idec, Bristol-Myers Squibb, Boehringer Mannheim, Genentech, GlaxoSmithKline, Eli Lilly, Merck & Co., Ortho-McNeill, Pfizer, Procter and Gamble, Roche, Wyeth, and Zelos Therapeutics. J. Brzezicki has received research support from and served as a speaker and consultant for Merck & Co. K. O'Brien, B. Soffer, A. Polis, S. Bird, A. Kaur, and S.P. Curtis are employees of Merck & Co. and own stock and/or hold stock options in the Company. H.S.B. Baraf, MD, The Center for Rheumatology and Bone Research; C. Fuentealba, MD, Hospital San Borja Arriarán; M. Greenwald, MD, Desert Medical Advances; J. Brzezicki, MD, Oddzial Reumatologii– Wojewodzki Szpital Zespolony; K. O'Brien, BS; B. Soffer, BA, Med, RA; A. Polis, MA; S. Bird, MS; A. Kaur, PhD; S.P. Curtis, MD, Merck & Co., Inc. Address reprint requests to Dr. H.S.B. Baraf, The Center for Rheumatology and Bone Research, 2730 University Boulevard West, Suite 306, Wheaton, MD 20902, USA, E-mail: hsbbaraf@mac.com Accepted for publication August 23, 2006.
|
