Background Prostanoid synthesis is catalysed by two distinct cyclooxygenase (COX) isoforms; COX-1 (constitutive) and COX-2 (inducible). NSAIDs such as aspirin, ibuprofen and indomethacin inhibit both COX isoforms. Etoricoxib has been characterised as a COX-2 selective inhibitor with doses up to 150 mg QD (100-fold selective in human whole blood assay).
Objectives Characterise the clinically active dose range and the longer term efficacy of etoricoxib in rheumatoid arthritis (RA).
Methods Double-blind, randomised, placebo-controlled study conducted in 54 centres worldwide in 581 RA patients. Following withdrawal of prestudy NSAIDs and demonstration of a worsening of disease activity, eligible patients were randomised to once daily oral therapy with either placebo (n = 123), etoricoxib 10 mg (n = 78), 60 mg (n = 126), 90 mg (n = 134), or 120 mg (n = 120) and assessed after 2, 4 and 8 weeks.
Results Over the initial 8-week period (Part I), patients taking etoricoxib 90 mg and 120 mg demonstrated similar efficacy, with both treatment groups showing significant improvements compared to placebo (average change from baseline p < 0.05) for the primary endpoints of patient and investigator global assessment of disease activity and key secondary endpoints of patient global assessment of pain and Stanford Health Assessment Questionnaire (HAQ) Disability Index. For the patient assessment of disease activity, there was -9.41, and -9.15 mm (VAS) mean difference vs. placebo (least-squares mean difference vs. placebo, responses averaged over weeks 2 to 8 for the 90 mg, and 120 mg etoricoxib treatment groups, respectively). Data demonstrating that longer term efficacy was maintained (up to 52 weeks) will be presented.
Etoricoxib was generally well-tolerated during Part I. There were no statistically significant trends for patients with one or more adverse events (AEs), serious AEs, drug-related serious AEs, or discontinuations due to AEs (p > 0.05, etoricoxib vs placebo). Safety (up to 52 weeks) was generally consistent with that observed during Part I.
Conclusion Etoricoxib 90–120 mg improved the symptoms of RA over 8 weeks and was well tolerated, with longer term efficacy data demonstrating maintenance of effect. Replicative phase III studies are ongoing to evaluate the efficacy and safety of etoricoxib in patients with RA.