Background Prostanoid synthesis is catalysed by two distinct cyclooxygenase (COX) isoforms; COX-1 (constitutive) and COX-2 (inducible). NSAIDs such as aspirin and ibuprofen 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 Evaluate long-term efficacy following dose range finding of etoricoxib in knee OA.
Methods Double-blind, randomised, placebo-controlled, multicenter study conducted in 617 knee OA patients. Patients with increased pain after NSAID withdrawal were allocated to qd oral etoricoxib 5 mg (N = 117), 10 mg (N = 114), 30 mg (N = 102), 60 mg (N = 112), 90 mg (N = 112) or placebo (N = 60). Following Part I (6 weeks), patients continued in double-blind continuation studies (total treatment 52 weeks). Patients receiving placebo, etoricoxib 5 and 10 mg in Part I were reallocated to etoricoxib 30-, 60-, 90 mg, or diclofenac 150 mg in the continuation studies. Etoricoxib 30-, 60-, and 90 mg remained constant over 52 weeks.
Results In Part I, etoricoxib 5-, 10-, 30-, 60-, and 90 mg demonstrated significantly greater efficacy than placebo for the primary endpoints (p < 0.05), with effect sizes exhibiting a strong, dose-related trend. For the subset of patients remaining in the etoricoxib 30-, 60-, 90 mg groups over 52 weeks, the treatment effect was generally maintained. Similar to the results in Part I, the 60- and 90-mg treatments were shown to be more effective than the 30-mg dose with respect to each of the 3 primary efficacy endpoints (WOMAC VA 3.0 pain subscale, patient and investigator global assessment of disease status).
Etoricoxib was generally well tolerated over 52-weeks. In Part I, the incidence of patient discontinuation due to adverse events (AEs) was not significantly different between MK-663 and placebo. There were no clinically significant dose-related trends across treatments with > = 1 AEs, drug-related AEs, serious AEs, or drug-related serious AEs. The safety results through 52 weeks were consistent with those in Part I, with no evidence of new types of AEs arising.
Conclusion Etoricoxib was generally well tolerated in doses up to 90 mg in patients with OA for up to 52 weeks, and resulted in sustained clinical efficacy.
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