in patients with or without concomitant DMARD and/or low- dose corticosteroid therapy (Matsumoto, Zhao, et al 2003). Etoricoxib exhibited comparable efficacy versus placebo in a duplicate international study (n = 891), although there was no significant difference between etoricoxib and naproxen. This discrepancy in results between the US and international studies may be due to variances in the use of concomitant therapies or result from underlying medical or cultural differences between the populations (Collantes et al 2002). Extensions of the US and international studies showed that the efficacy of etoricoxib and naproxen was maintained through 52 weeks (Matsumoto, Collantes, et al 2003). Etoricoxib in the treatment of acute gouty arthritis Within the EU, etoricoxib is approved for the treatment of acute gouty arthritis at a dosage of 120 mg QD during the acute symptomatic period (EMEA 2005a). This approval is based on the results of two clinical trials which indicate that etoricoxib and indomethacin have comparable efficacy in treating this painful condition. (Rubin et al 2004; Schumacher et al 2002) Duplicate randomized studies enrolling a total of 339 patients presenting with acute gout showed that etoricoxib 120 mg QD or indomethacin 50 mg TID for 8 days produced comparable improvements in pain in the affected joint, patient and investigator assessments of global treatment response, and joint tenderness and swelling (Rubin et al 2004; Schumacher et al 2002). The onset of pain relief was rapid, with similar benefit reported within 4 hours of the first dose of etoricoxib or indomethacin (Rubin et al 2004; Schumacher et al 2002). An exploratory analysis in one study (n = 189) showed that etoricoxib produced significantly greater resolution of erythema after 8 days compared with indomethacin (p = 0.038) (Figure 3) (Rubin et al 2004), and post-hoc analysis of both studies indicated that the effectiveness of etoricoxib was due to significant antiinflammatory and analgesic activity, and not natural resolution of the disease (Boice et al 2004). Etoricoxib in the treatment of other painful conditions The efficacy of etoricoxib has been established in a variety of other painful conditions including ankylosing spondylitis (AS), LBP, acute postoperative pain, and primary dysmenorrhea. In a randomized study in 387 patients with AS, etoricoxib 90 mg or 120 mg QD showed superior efficacy to naproxen 500 mg twice daily (BID) (p < 0.05) or placebo (p < 0.001) at 6 weeks with respect to spinal pain, Therapeutics and Clinical Risk Management 2006:2(1) 100 ()%90 am80 e tryh 70 itnE 60 o Jy 50 d tuS 40 ith 30 w tsn 20 e i ta 10 P 0 * 17.7 6.9 Day 8 92.0 91.8 Etoricoxib for arthritis and pain Etoricoxib 120 mg QD (n = 103) Indomethacin 50 mg TID (n = 86) 51.0 55.4 15.8 27.1 Baseline Day 2 Day 5 Study Day Figure 3 Improvement in study joint erythema in patients with acute gout treated with etoricoxib or indomethacin for 8 days.This randomized, double- blind study compared the efficacy of etoricoxib 120 mg QD versus indomethacin 50 mg TID in 189 patients experiencing an acute attack (≤ 48 hours) of gout.The treatments produced comparable efficacy on all primary and secondary endpoints; however, a prespecified exploratory analysis illustrated here showed that etoricoxib was associated with a greater reduction in the incidence of erythema than indomethacin, with the different reaching statistical significance at completion of the study period. Copyright © 2004. Reproduced with permission from Rubin BR, Burton R, Navarra S, et al. 2004. Efficacy and safety profile of treatment with etoricoxib 120 mg once daily compared with indomethacin 50 mg three times daily in acute gout: a randomized controlled trial. Arthritis Rheum, 50:598–606. * p < 0.05. Abbreviations: QD, every day; TID, three times daily. global disease activity, and function (van der Heijde et al 2005). Significant pain relief versus placebo was observed within 4 hours of the first dose of etoricoxib 90 mg QD and following the second dose of etoricoxib 120 mg QD, and superior efficacy versus naproxen was maintained over 52 weeks. In a post-hoc analysis of data from this study, etoricoxib and naproxen improved axial symptoms in patients with or without peripheral disease, although patients without peripheral arthritis showed greater spinal improvement (Gossec et al 2005). In addition, a small study (n = 22) suggested that etoricoxib 90 mg QD may reduce the need for biologic therapy in patients with severe previously NSAID-refractory AS (Jarrett et al 2004). Duplicate 12-week studies in a total of 644 patients with chronic LBP showed that etoricoxib 60 or 90 mg QD produced significant improvements in pain intensity relative to placebo at the primary 4-week time point (p < 0.001), and in most secondary endpoints at 12 weeks (Birbara et al 2003; Pallay et al 2004). Clinical benefit was achieved as early as 1 week and was maintained throughout the 3 months of the study, with no significant differences between etoricoxib dosage groups. In 1147 patients with acute LBP who completed an open, nonrandomized 6-week study of etoricoxib 60 to 120 mg QD, improvements from baseline in physical activity were observed at 2 weeks and improvements in lumbar pain and functional capacity were 49