Etoricoxib (Arcoxia®▼)

VERDICT & SUMMARY Etoricoxib (Arcoxia®▼)

For the treatment of osteoarthritis,

Committee’s Verdict: CATEGORY A (Q3) BNF: 10.1.1 Etoricoxib is suitable for prescribing in primary care. Prescribers should bear in mind the warnings from the European Medicines Agency about cardiovascular safety of all the COX-II selective inhibitors, and follow the advice from the Committee for Safety on Medicines regarding their use. Category A: suitable for prescribing in primary care Q rating: The evidence for the efficacy and safety of etoricoxib was Q2 Q1 considered to be relatively strong, based on 13 randomised controlled trials higher place higher place weaker evidence stronger evidence comparing etoricoxib with placebo and other non-steroidal anti-inflammatory drugs (NSAIDs). The lack of evidence for cardiovascular safety and limitations for use only in patients at “high risk” of gastrointestinal events (NICE guidance) give it a low place in therapy. Q4 Q3 lower place lower place The Q rating relates to the drug’s position on the effectiveness indicator grid. weaker evidence stronger evidence The strength of the evidence is determined by the quality and quantity of studies that show significant efficacy of the drug compared with placebo or alternative Place in primary care therapy in therapy. Its place in therapy in primary care takes into account safety and practical Strength of evidence for efficacy aspects of using the drug in primary care, alternative options, relevant NICE guidance, and the need for secondary care input.

MTRAC reviewed this drug because of concerns about the cardiovascular safety of COX-II selective inhibitors. Licensed indication Clinical efficacy Etoricoxib is licensed for:1 Osteoarthritis • osteoarthritis (60 mg once daily) Four double-blind, randomised controlled trials (RCTs) • rheumatoid arthritis (90 mg once daily) (n = 2,162; duration six to 12 weeks) evaluated etoricoxib for the treatment of OA of the knee or hip in • the pain and signs of inflammation associated with 2-6 acute gouty arthritis (120 mg once daily) adults with a confirmed diagnosis of OA. In two of the studies (n = 1,017), the licensed dose of 60 mg Background information daily was used; the other studies used either 30 mg Osteoarthritis (OA) is a chronic joint disorder involving daily or a range of doses up to 90 mg daily. damage to the articular cartilage of the knees, hips, Comparators were placebo, diclofenac 150 mg daily, hands. Treatment is symptomatic, and includes ibuprofen 2,400 mg daily or naproxen 1,000 daily. The paracetamol, codeine and dihydrocodeine, and primary outcomes were the WOMAC pain subscale NSAIDs, which are considered third-line agents. and the patient’s and investigator’s assessment of disease status and response to therapy. In these Rheumatoid arthritis (RA) involves persistent synovial studies, etoricoxib was significantly more efficacious inflammation of peripheral joints affecting about 1% to than placebo for all primary outcomes (p ≤ 0.05) and 2% of adults in the UK. Therapy includes symptomatic was comparable to all three other NSAIDs. In a 52- pain relief (usually with NSAIDs) and disease- modifying drugs (DMARDs). week extension to one study, the benefits were maintained.4 Gout is an inflammation of joints, bursas, and tendon sheaths caused by the accumulation of crystals of Rheumatoid Arthritis Two double-blind RCTs with the same design sodium urate monohydrate. The treatment of choice for acute attacks is a full dose of an NSAID. compared the efficacy and safety of etoricoxib 90 mg daily with placebo and naproxen 1,000 mg daily in Colchicine is used second-line, as it is associated with patients with RA (n = 1,707; duration 12 weeks).7,8 toxicity at higher doses. The primary outcomes were patient’s and Etoricoxib is an NSAID that is relatively selective for investigator’s global assessment of disease activity, the COX-II isozyme, which may make it less likely to and the number of tender and swollen joints. In both cause gastrointestinal adverse events compared with trials, etoricoxib was more effective than placebo for all traditional NSAIDs. primary and secondary outcomes (p < 0.05), and at

July 2006 Page 1 of 2 least as effective as naproxen, being superior in one of Additional information the trials7 but not in the other.8 At current prices one year’s treatment with: Acute gout Two double-blind RCTs (n = 339; duration 8 days) • celecoxib 200 mg daily costs £262 compared etoricoxib 120 mg daily with indometacin • etoricoxib 60 mg daily costs £299 150 mg daily.9,10 No placebo arm was included. The • lumiracoxib 100 mg daily costs £209 patient’s assessment of pain was the primary outcome. References In both studies the active treatments were comparable in reducing pain and inflammation, with significant pain 1. MSD. Arcoxia 60 mg, 90 mg and 120 mg film-coated tablets. relief evident within four hours after the first dose of Summary of Product Characteristics 2005. 2. Leung AT, Malmstrom K, Gallacher AE et al. Efficacy and treatment. tolerability profile of etoricoxib in patients with osteoarthritis: Adverse effects A randomized, double-blind, placebo and active-comparator controlled 12-week efficacy trial. Curr Med Res Opin The most commonly reported adverse events in the 2002;18:49-58. trials were related to the gastrointestinal tract and 3. Zacher J, Feldman D, Gerli R et al. A comparison of the therapeutic efficacy and tolerability of etoricoxib and included nausea, diarrhoea, dyspepsia and upper diclofenac in patients with osteoarthritis. Curr Med Res Opin abdominal pain. Other events included oedema, 2003;19:725-36. dizziness, headache, hypertension, fatigue and 4. Curtis SP, Bockow B, Fisher C et al. Etoricoxib in the increases in liver enzymes. treatment of osteoarthritis over 52-weeks: a double-blind, active-comparator controlled trial. BMC Musculoskelet. Two studies assessed gastro-duodenal ulceration by Disord 2005;6:58. endoscopy in adults with OA (n = 1,422; duration 12 5. Wiesenhutter CW, Boice JA, Ko A et al. Evaluation of the weeks).11,12 The cumulative incidence of ulcers (≥ 3 comparative efficacy of etoricoxib and ibuprofen for mm) was 7.4% to 8.1% with etoricoxib, 25% with treatment of patients with osteoarthritis: A randomized, naproxen, 17% with ibuprofen, and 1.4 to 1.9% with double-blind, placebo-controlled trial. Mayo Clin Proc 2005;80:470-9. placebo. The incidence with etoricoxib was 6. Gottesdiener K, Schnitzer T, Fisher C et al. Results of a significantly higher than with placebo (p = 0.003), and randomized, dose-ranging trial of etoricoxib in patients with lower than with naproxen or ibuprofen (p < 0.01). osteoarthritis. Rheumatology (Oxford) 2002;41:1052-61. 7. Matsumoto AK, Melian A, Mandel DR et al. A randomized, A cumulative analysis of ten RCTs involving about controlled, clinical trial of etoricoxib in the treatment of 6,000 patients found confirmed upper gastrointestinal rheumatoid arthritis. J Rheumatol 2002;29:1623-30. events among 0.95% patients treated with etoricoxib, 8. Collantes E, Curtis SP, Lee KW et al. A multinational compared with 2.2% treated with traditional NSAIDs randomized, controlled, clinical trial of etoricoxib in the (absolute risk difference 1.25%; NNT = 80) and 0% treatment of rheumatoid arthritis. BMC Fam Pract 2002;3:10. 12 9. Schumacher JR HR, Boice JA, Daikh DI et al. Randomised with placebo. double blind trial of etoricoxib and indometacin in treatment No evidence on cardiovascular safety of etoricoxib has of acute gouty arthritis. BMJ 2002;324:1488-92. been published; two large studies, EDGE and METAL, 10. Rubin BR, Burton R, Navarra S et al. Efficacy and safety profile of treatment with etoricoxib 120 mg once daily are ongoing to address this issue. See the SPC for 1 compared with indomethacin 50 mg three times daily in further details on adverse events. acute gout: a randomized controlled trial. Arthritis Rheum 2004;50:598-606. Guidance from NICE and other advisory bodies 11. Hunt RH, Harper S, Watson DJ et al. The gastrointestinal NICE guidance (2001) recommends use of COX-II safety of the COX-2 selective inhibitor etoricoxib assessed by both endoscopy and analysis of upper gastrointestinal selective agents instead of traditional NSAIDs only in events. Am J Gastroenterol 2003;98:1725-33. patients at “high risk” of developing serious 12. Hunt RH, Harper S, Callegari P et al. Complementary 13 gastrointestinal problems. studies of the gastrointestinal safety of the cyclo-oxygenase- 2-selective inhibitor etoricoxib. Aliment Pharmacol Ther Following review of the cardiovascular safety of the 2003;17:201-10. COX-II agents by the European Medicines Agency, the 13. National Institute for Clinical Excellence. Guidance on the Committee on Safety of Medicines has published use of cyclo-oxygenase (Cox) II selective inhibitors, precautions with regard to prescribing of these drugs.14 celecoxib, rofecoxib, meloxicam and etodolac for osteoarthritis and rheumatoid arthritis. Technology Appraisal Etoricoxib should not be used in patients with Guidance No. 27. 2001. uncontrolled hypertension, and blood pressure should 14. CSM/MCA. Updated advice on the safety of selective be monitored. COX-2 inhibitors. 17 February 2005. www.mhra.gov.uk.

Launch date: February 2002 Manufacturer: Merck Sharp & Dohme PL 0025/0422,23,24 WARNING: This sheet should be read in conjunction with the Summary of Product Characteristics This guidance is based upon the published information available in English at the time the drug was considered. It remains open to review in the event of significant new evidence emerging. MTRAC can be contacted at the Dept. of Medicines Management, Keele University, Keele, Staffs ST5 5BG Tel: 01782 584131 Fax: 01782 713586 Email: [email protected] Web: www.mtrac.co.uk