title: Gastrointestinal side effects of etoricoxib in patients with osteoarthritis: results of the Etoricoxib versus Diclofenac Sodium Gastrointestinal Tolerability and Effectiveness (EDGE) trial.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Rheumatology and Bone Research, Wheaton, Maryland 20902, USA. hsbbaraf@mac.com
authors.forename: Herbert S B
authors.initials: HS
authors.lastname: Baraf
authors.forename: Carlos
authors.initials: C
authors.lastname: Fuentealba
authors.forename: Maria
authors.initials: M
authors.lastname: Greenwald
authors.forename: Jan
authors.initials: J
authors.lastname: Brzezicki
authors.forename: Katherine
authors.initials: K
authors.lastname: O'Brien
authors.forename: Beth
authors.initials: B
authors.lastname: Soffer
authors.forename: Adam
authors.initials: A
authors.lastname: Polis
authors.forename: Steven
authors.initials: S
authors.lastname: Bird
authors.forename: Amarjot
authors.initials: A
authors.lastname: Kaur
authors.forename: Sean P
authors.initials: SP
authors.lastname: Curtis
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004008:Diclofenac / Q000009:adverse effects*; D004311:Double-Blind Method; D000077613:Etoricoxib; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy*; D011725:Pyridines / Q000009:adverse effects*; D013450:Sulfones / Q000009:adverse effects*; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011725:Pyridines; D013450:Sulfones; D004008:Diclofenac; D000077613:Etoricoxib