Brooks and Kubler seen at 6 weeks (p < 0.001, each comparison) (Hernandez- Garduño et al 2005). Etoricoxib is as effective as high-dose diclofenac in treating chronic LBP. In a 4-week, randomized, double- blind, parallel-group study of 446 patients with chronic LBP (Quebec Task Force on Spinal Disorders Class 1 or 2), etoricoxib 60 mg QD was as effective as diclofenac 50 mg TID in relieving LBP as assessed by the Lower Back Pain Intensity Scale (LBP-IS). The time-weighted average change from baseline over 4 weeks for the LBP-IS was 33 mm in each group (95% confidence interval [CI] –36.25, –29.63). Both etoricoxib and diclofenac improved measures of physical functioning, and were well-tolerated throughout the trial (Zerbini et al 2005). A randomized single dose-response study in 398 patients with moderate to severe acute pain following dental surgery showed that etoricoxib 120 mg was the optimal dosage for this indication. Overall, 93.4% of patients receiving a single dose of etoricoxib 120 mg had perceptible pain relief, with a median time to pain relief of 0.4 hours and median time to use of rescue medication of more than 24 hours (p < 0.001 versus placebo and p < 0.05 versus etoricoxib 60 mg for all comparisons) (Malmstrom, Sapre, et al 2004). Subsequent studies have shown that a single dose of etoricoxib 120 mg has greater overall analgesic efficacy in this setting than oxycodone 10 mg/acetaminophen 650 mg (Chang et al 2004; Malmstrom et al 2005) or codeine 60 mg/acetaminophen 600 mg (Malmstrom, Kotey, et al 2004; Malmstrom et al 2005), and comparable efficacy to naproxen 550 mg (Malmstrom, Kotey, et al 2004). A recent study (n = 228) also demonstrated comparable pain relief with a single dose of etoricoxib 120 mg or extended-release naproxen 1000 mg administered within 72 hours of knee or hip replacement surgery, and superior analgesic efficacy with etoricoxib 120 mg QD versus placebo over 7 days following surgery (p < 0.001) (no active comparator group was available for the latter analysis) (Rasmussen et al 2004). Finally, a single dose of etoricoxib 120 mg showed analgesic efficacy superior to placebo, and comparable with naproxen 550 mg, in a randomized study in 73 women with primary dysmenorrhea (Malmstrom et al 2003). Tolerability and patient acceptability Clinical trial data indicates that etoricoxib has a favorable tolerability profile and is associated with an improved quality of life (Hunsche et al 2002; Ramos-Remus et al 2004). Moreover, clinical trial extensions showed that the tolerability profile of etoricoxib was maintained without 50 notable safety findings during prolonged treatment for a total of 52 to 174 weeks (Fisher et al 2001, 2003; Curtis, Losada, et al 2003; Matsumoto, Collantes, et al 2003; Reginster et al 2004; van der Heijde et al 2005). Based on clinical experience with other NSAIDs, issues of particular interest in etoricoxib trials included gastrointestinal tolerability, renovascular effects, and cardiovascular safety. Gastrointestinal tolerability Several clinical trials reported superior gastrointestinal tolerability with etoricoxib compared with traditional NSAIDs. A 12-week study in 501 patients with OA showed that etoricoxib 60 mg QD was associated with a lower rate of ‘nuisance’ gastrointestinal adverse events (eg, abdominal pain, dyspepsia) (20.1% versus 33.0%) and fewer upper gastrointestinal perforations, ulcers, or bleeding (PUBs) (0 versus 5 events) compared with naproxen 500 mg BID (Leung et al 2002). Moreover a pooled analysis of this and a duplicate study indicates that the favorable gastrointestinal tolerability of etoricoxib is maintained during long-term treatment over 138 weeks (0.8% versus 5.9% PUBs) (Reginster et al 2004). The EDGE study reported a lower rate of discontinuations due to gastrointestinal adverse events with etoricoxib 90 mg QD than with diclofenac 50 mg TID in patients with OA (relative risk [RR], 0.50; p < 0.001) (Baraf et al 2004). In this study consistent benefit was also observed within patient subgroups at risk for gastrointestinal adverse events, including patients using concomitant aspirin or continuing or initiating gastroprotective therapy (Baraf et al 2005a). There was no difference with respect to the incidence of PUBs or new use of gastroprotective agents in the EDGE study (Merck 2005); however, this was not a prespecified endpoint and the analysis was confounded by use of aspirin and gastroprotective agents. An 8-day study in 189 patients with acute gout showed that etoricoxib 120 mg QD was associated with a lower rate of drug-related gastrointestinal adverse events than indomethacin 50 mg TID (7.8% versus 18.6%) (Rubin et al 2004). A 4-week safety study in 62 healthy volunteers demonstrated that daily fecal blood loss with etoricoxib 120 mg QD was comparable with placebo and lower than with ibuprofen 800 mg TID (p < 0.001) (Hunt, Harper, Callegari, et al 2003). Results from two large 12-week endoscopy studies in patients with OA or RA showed that etoricoxib 120 mg QD was associated with a lower cumulative incidence of gastroduodenal ulcers (≥ 3 mm) and a smaller increase in gastroduodenal erosions than naproxen 500 mg BID (Hunt, Harper, Callegari, et al 2003) or ibuprofen 800 mg TID Therapeutics and Clinical Risk Management 2006:2(1)