Brooks and Kubler patients with hip, knee, hand, or spine OA, showed sustained and comparable improvements in Patient’s Global Assessment of Disease Status (PGADS) with etoricoxib 90 mg QD or diclofenac 50 mg TID at 12 months (Baraf et al 2004). Two randomized, double-blind, 12-week studies in a total of 997 patients with hip or knee OA showed that etoricoxib 60 mg QD and naproxen 500 mg TID were of comparable efficacy, and superior to placebo, as measured by WOMAC pain and physical function subscales and PGADS (Fisher et al 2001; Leung et al 2002). In addition, patients receiving etoricoxib or diclofenac also experienced treatment-related significant improvements in social and emotional quality of life and vitality (Hunsche et al 2002). Early improvements in patient condition were observed 2 days after initiating etoricoxib treatment (Leung et al 2002) and then maintained through up to 138 weeks on study extensions (Reginster et al 2004). The recommended etoricoxib dosage for OA is 60 mg QD (EMEA 2005a); however, etoricoxib also appears to offer effective pain relief at lower doses consistent with the initial dose-ranging findings (Gottesdiener, 2002). A recent randomized trial in 528 patients with hip or knee OA demonstrated that the efficacy of etoricoxib 30 mg QD was comparable with that of ibuprofen 800 mg TID over 12 weeks on the WOMAC pain and physical functioning subscales and PGADS (p < 0.001 versus placebo for all comparisons) (Wiesenhutter et al 2005). Etoricoxib in the treatment of rheumatoid arthritis The efficacy of etoricoxib is similar to, or greater than, that of conventional NSAIDs in patients with RA. In a randomized study evaluating etoricoxib doses of 10, 60, 90, and 120 mg QD in 581 adults with RA, patients receiving etoricoxib 90 mg or 120 mg QD for 8 weeks achieved similar improvements in the primary endpoints of patient and investigator global assessment of disease activity. Both treatment groups showed significant improvements compared with placebo (average change from baseline p < 0.05) (Curtis et al 2001). Moreover, in extensions to this study the efficacy of etoricoxib 90 mg or 120 mg QD was maintained, and was similar to that of diclofenac 50 mg TID, over the subsequent 166 weeks (Curtis et al 2001; Curtis, Losada, et al 2003). Since etoricoxib 90 mg QD produced maximal benefit in this study, with no additional efficacy at higher doses, this is considered the optimal dosage for RA (EMEA 2005a). In a randomized study in 816 patients with RA in the US, etoricoxib 90 mg QD was more effective than naproxen 48 500 mg TID (p < 0.05) or placebo (p < 0.01) over 12 weeks for all primary and most secondary endpoints (Figure 2), including the percentage of patients who achieved an American College of Rheumatology 20% Response Criteria (ACR20) response (57.9%, 46.8%, and 27.4%, respectively) (Matsumoto et al 2002). The efficacy of etoricoxib was evident after 2 weeks (Matsumoto et al 2002), and was similar 5 12 12 0 E ±S –5 e gn –10 a ch –15 n ae –20 M –25 –30 0.0 –0.2 SE –0.4 e± –0.6 g an –0.8 h c –1.0 n ae –1.2 M –1.4 –1.6 S R 2 4 8 Week in study Patient global assessment of disease activity (0 to 100 VAS scale) = Placebo = etoricoxib 90 mg QID = naproxen 500 mg TID S R 2 4 8 Week in study Investigator global assessment of disease activity (0 to 4 Likert scale) S = screening visit R = randomization visit (baseline) Figure 2 Global assessment results for etoricoxib versus placebo and naproxen in patients with rheumatoid arthritis. In this randomized, double-blind, controlled study, 816 adult patients with rheumatoid arthritis were randomized to receive etoricoxib 90 mg QD (n = 323), naproxen 500 mg BID (n = 170) or placebo (n = 323) for 12 weeks. Etoricoxib demonstrated superior efficacy on all primary endpoints compared with naproxen (p < 0.05) or placebo (p < 0.01). Efficacy was evident after 2 weeks and was maintained throughout the study period, as illustrated here for two primary endpoints: patient global assessment of disease activity (top panel) and investigator global assessment of disease activity (bottom panel). Copyright © 2003. Reproduced with permission from Matsumoto AK, Melian A, Mandel DR, et al. 2002.A randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis. J Rheumatol, 29:1623–30. Abbreviations: BID, twice daily; QD, every day; VAS, visual analog scale. Therapeutics and Clinical Risk Management 2006:2(1)