Etoricoxib in the treatment of osteoarthritis over 52-weeks: a double-blind, active-comparator controlled trial [NCT00242489]

Abstract

Background: The aim of this study was to evaluate the long-term efficacy and tolerability of etoricoxib, a COX-2 selective inhibitor, in osteoarthritis (OA) patients.

Methods: A double-blind, randomized, multicenter study was conducted in 617 patients with OA of the knee. The base study was 14 weeks in duration and consisted of 2 parts; in Part I (6 weeks), patients were allocated to once daily oral etoricoxib 5, 10, 30, 60, 90 mg or placebo. In Part II (8 weeks); the placebo, etoricoxib 5 and 10 mg groups were reallocated to etoricoxib 30, 60, or 90 mg qd or diclofenac 50 mg t.i.d. Treatment was continued for consecutive 12 and 26 week extensions. Primary efficacy endpoints were the WOMAC VA 3.0 pain subscale and investigator global assessment of disease status. Safety and tolerability were assessed by collecting adverse events throughout the study.

Results: Compared with placebo, the etoricoxib groups displayed significant (p < 0.05), dose-dependent efficacy for all primary endpoints in Part I; efficacy was maintained throughout the 52 weeks of the study. During the 46-week active-comparator controlled period, the etoricoxib groups demonstrated clinical efficacy that was similar to that of diclofenac 150 mg and was generally well tolerated, with a lower incidence of gastrointestinal (GI) nuisance symptoms compared with diclofenac (13.1, 14.7, and 13.5% for etoricoxib 30, 60, and 90 mg, respectively compared with 22.5% for diclofenac).

Conclusion: In this extension study, etoricoxib, at doses ranging from 30 to 90 mg, demonstrated a maintenance of significant clinical efficacy in patients with OA through 52 weeks of treatment. Etoricoxib displayed clinical efficacy similar to diclofenac 150 mg and was generally well tolerated.

Trial registration: ClinicalTrials.gov NCT00242489.

Figures

Figure 1

Study Design. The patient flow during the entire 52-week period is illustrated. The efficacy and safety evaluation for this report is based on data from the 46-week active-comparator controlled period.

Figure 2

Patient accounting. † Number represents any patient who discontinued during the active comparator controlled period. Percent is calculated using the number of patients that entered the first extension as the denominator. ‡ Other Reasons include lost to follow-up, patient moved, patient withdrew consent, or protocol deviation.

Figure 3

Primary efficacy endpoints from during the active comparator controlled period (weeks 6 to 52). This is a comparison of etoricoxib 30, 60, and 90 mg with diclofenac 150 mg during the active comparator controlled extension periods. LS Mean Change from Baseline (Randomization) is shown. Modified intention-to-treat approach with last value carried forward was used. The number of patients at later visits (≥34 weeks) was small. Data should, therefore, be interpreted with caution. SE = Standard error. = 30 mg etoricoxib; = 60 mg etoricoxib; = 90 mg etoricoxib; = 150 mg diclofenac.

Figure 4

Primary endpoints evaluating efficacy of etoricoxib. LS Mean Change from Baseline is shown for patients receiving 30, 60 or 90 mg etoricoxib for up to 52 weeks. Modified Intention-to-Treat Approach With Last Value Carried Forward was performed. As the numbers of patients were small and decreased over time, data should be interpreted with caution. Screening (S) to baseline (R) = NSAID washout period; SE = Standard error ○ = 30 mg etoricoxib; * = 60 mg etoricoxib; ◆ = 90 mg etoricoxib.