title: Further assessment of the clinically effective dose range of etoricoxib: a randomized, double-blinded, placebo-controlled trial in rheumatoid arthritis.
abstract: OBJECTIVE
  To further assess the clinically active dose range of etoricoxib, a COX-2 selective inhibitor, in rheumatoid arthritis (RA).
  
  
  METHODS
  RA patients were randomized to etoricoxib 10, 30, 60, or 90 mg or placebo in a double-blind, 12-week study. DMARDs (methotrexate, biologics) or low-dose corticosteroids were allowed in stable doses. The primary endpoint was the proportion of patients completing the study and achieving an American College of Rheumatology 20% (ACR20) response. Secondary endpoints included individual components of the ACR index and Patient Global Assessment of Pain. Safety was assessed by physical exam and adverse experiences (AEs) occurrences.
  
  
  RESULTS
  Etoricoxib 90 mg was the only dose to reach a statistically significant difference from placebo (p < 0.001) on the primary endpoint; etoricoxib 60 mg approached significance (p = 0.057). Significant pain improvement vs. placebo was observed with etoricoxib 90 mg (p < 0.001), 60 mg (p = 0.018), and 30 mg (p = 0.017). Despite the use of background biologics and corticosteroids, a dose response was still apparent. A higher proportion of etoricoxib 60 and 90 mg patients had renovascular AEs (i.e., edema and hypertension) compared with placebo, although discontinuations for renovascular AEs were rare. Etoricoxib 90 mg had a higher incidence of serious AEs (n = 5; 1 was considered drug-related) versus placebo (n = 0).
  
  
  CONCLUSIONS
  The present study was not powered to detect differences in cardiovascular or gastrointestinal safety by dose. Additionally, further research is needed to clarify the role of doses less than the etoricoxib 90 mg dose for pain management in RA patients.
  
  
  CONCLUSIONS
  Etoricoxib 90 mg demonstrated statistically superior efficacy (ACR20) compared with placebo and numerical superiority over the other doses of etoricoxib studied. Etoricoxib 30 and 60 mg demonstrated significant pain improvement versus placebo, suggesting utility for some patients.
authors: Desert Medical Advances, Palm Desert, CA, USA. bdelph@dc.rr.com
authors: M
authors: M
authors: Greenwald
authors: P M
authors: PM
authors: Peloso
authors: D
authors: D
authors: Mandel
authors: O
authors: O
authors: Soto
authors: A
authors: A
authors: Mehta
authors: N
authors: N
authors: Frontera
authors: J A
authors: JA
authors: Boice
authors: X J
authors: XJ
authors: Zhan
authors: S P
authors: SP
authors: Curtis
mesh_terms: D000368:Aged; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000077613:Etoricoxib; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D012213:Rheumatic Fever / Q000188:drug therapy* / Q000503:physiopathology; D013450:Sulfones / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011725:Pyridines; D013450:Sulfones; D000077613:Etoricoxib