Etoricoxib for arthritis and pain management

Peter Brooks, Paul Kubler, Peter Brooks, Paul Kubler

Abstract

Nonsteroidal antiinflammatory drugs (NSAIDs), including selective cyclooxygenase (COX)-2 inhibitors, have come to play an important role in the pharmacologic management of arthritis and pain. Clinical trials have established the efficacy of etoricoxib in osteoarthritis, rheumatoid arthritis, acute gouty arthritis, ankylosing spondylitis, low back pain, acute postoperative pain, and primary dysmenorrhea. Comparative studies indicate at least similar efficacy with etoricoxib versus traditional NSAIDs. Etoricoxib was generally well tolerated in these studies with no new safety findings during long-term administration. The gastrointestinal, renovascular, and cardiovascular tolerability profiles of etoricoxib have been evaluated in large patient datasets, and further insight into the cardiovascular tolerability of etoricoxib and diclofenac will be gained from a large ongoing cardiovascular outcomes program (MEDAL). The available data suggest that etoricoxib is an efficacious alternative in the management of arthritis and pain, with the potential advantages of convenient once-daily administration and superior gastrointestinal tolerability compared with traditional NSAIDs.

Figures

Figure 1
Figure 1
Osteoarthritis PGART 4 hours ± 15 minutes after the first dose of etoricoxib versus diclofenac. This randomized, double-blind, parallel-group study evaluated the efficacy and tolerability of etoricoxib 60 mg QD versus diclofenac 50 mg TID over 6 weeks in 516 patients with hip or knee osteoarthritis. The treatments were of comparable efficacy on all primary and secondary efficacy endpoints (data not shown), except for the analysis of early efficacy illustrated here in which a greater percentage of patients reported good or excellent PGART responses within 4 hours of receiving their first dose of etoricoxib compared with diclofenac. Copyright © 2003. Reproduced with permission from Zacher J, Feldman D, Gerli R, et al. 2003. A comparison of the therapeutic efficacy and tolerability of etoricoxib and diclofenac in patients with osteoarthritis. Curr Med Res Opin, 19:725–36. * p = 0.007 for good or excellent PGART with etoricoxib versus diclofenac. Abbreviations: QD, every day; PGART, Patient Global Assessment of Response to Therapy; TID, three times daily.
Figure 2
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 © 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.
Figure 3
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 Abbreviations: QD, every day; TID, three times daily.
Figure 4
Figure 4
Clinical summary of etoricoxib in arthritis and pain management. *Greater efficacy defined here as a statistically significant benefit with etoricoxib versus active comparator in an efficacy study. † An active comparator study has not been performed. Abbreviations: EDGE, Etoricoxib versus diclofenac sodium gastrointestinal tolerability and effectiveness study; MEDAL, Multinational etoricoxib and diclofenac arthritis long-term study; NSAIDs, nonsteroidal antiinflammatory drug.

References

    1. Agrawal NG, Matthews CZ, Mazenko RS, et al. Pharmacokinetics of etoricoxib in patients with renal impairment. J Clin Pharmacol. 2004a;44:48–58.
    1. Agrawal NG, Matthews CZ, Mazenko RS, et al. The effects of modifying in vivo cytochrome P450 3A (CYP3A) activity on etoricoxib pharmacokinetics and of etoricoxib administration on CYP3A activity. J Clin Pharmacol. 2004b;44:1125–31.
    1. Agrawal NG, Porras AG, Matthews CZ, et al. Single- and multiple-dose pharmacokinetics of etoricoxib a selective inhibitor of cyclooxygenase-2, in man. J Clin Pharmacol. 2003;43:268–76.
    1. Agrawal NG, Rose MJ, Matthews CZ, et al. Pharmacokinetics of etoricoxib in patients with hepatic impairment. J Clin Pharmacol. 2003;43:1136–48.
    1. [ACRCCG] American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Guidelines for the initial evaluation of the adult patient with acute musculoskeletal symptoms. Arthritis Rheum. 1996;39:1–8.
    1. [ACRSOG] American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum. 2000;43:1905–15.
    1. [ACRRAG] American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum. 2002;46:328–46.
    1. Argoff CE. Pharmacologic management of chronic pain. J Am Osteopath Assoc. 2002;102:S21–7.
    1. Baraf H, Fuentealba C, Greenwald M, et al. Gastrointestinal tolerability of etoricoxib compared with diclofenac sodium in subgroups of patients at risk for gastrointestinal side effects from the edge study [abstract]. Annual Meeting of the European League Against Rheumatism; 8–11 June 2005; Vienna, Austria. 2005a. SAT0277.
    1. Baraf H, Fuentealba C, Greenwald M, et al. Cardiovascular event rates with etoricoxib and comparator NSAIDs in the edge study and the overall etoricoxib development program [abstract]. Annual Meeting of the European League Against Rheumatism; 8-11 June 2005; Vienna, Austria. 2005b. SAT0276.
    1. Baraf HSB, Fuentealba C, Greenwald M, et al. Tolerability and effectiveness of etoricoxib compared with diclofenac sodium in patients with osteoarthritis: a randomized controlled study (EDGE trial) [abstract]. American College of Rheumatology 68th Annual Scientific Meeting; 16–21 October 2004; San Antonio, TX, USA. 2004. 832.
    1. Birbara CA, Puopolo AD, Munoz DR, et al. Treatment of chronic low back pain with etoricoxib, a new cyclo-oxygenase-2 selective inhibitor: improvement in pain and disability—a randomized, placebo-controlled, 3-month trial. J Pain. 2003;4:307–15.
    1. Boice JA, Ng J, Rubin BR, et al. The spontaneous resolution of acute gouty arthritis does not significantly contribute to the potent and comparable antiinflammatory and analgesic effect of etoricoxib of indomethacin over the first four days of treatment [abstract]. American College of Rheumatology 68th Annual Scientific Meeting; 16–21 October 2004; San Antonio, TX USA. 2004. 809.
    1. Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med. 2000;343:1520–8.
    1. Bresalier RS, Sandler RS, Quan H, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005;352:1092–102.
    1. Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001;345:1809–17.
    1. Chang DJ, Desjardins PJ, King TR, et al. The analgesic efficacy of etoricoxib compared with oxycodone/acetaminophen in an acute postoperative pain model: a randomized, double-blind clinical trial. Anesth Analg. 2004;99:807–15.
    1. Clark DW, Layton D, Shakir SA. Do some inhibitors of COX-2 increase the risk of thromboembolic events?: Linking pharmacology with pharmacoepidemiology. Drug Saf. 2004;27:427–56.
    1. Collantes E, Curtis SP, Lee KW, et al. A multinational randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis [ISRCTN25142273] BMC Fam Pract. 2002;3:10.
    1. Curtis SP, Losada B, Bosi-Ferraz M, et al. Etoricoxib and diclofenac demonstrate similar efficacy in a 174-week randomized study of rheumatoid arthritis patients [poster]. American College of Rheumatology 67th Annual Scientific Meeting; 23–28 October 2003; Orlando, FL, USA. 2003a. p. 213.
    1. Curtis SP, Maldonado-Cocco J, Losada BR, et al. Treatment with etoricoxib (MK-0663), a COX-2-selective inhibitor, resulted in maintenance of clinical improvement in rheumatoid arthritis [abstract]. Annual Meeting of the European League Against Rheumatism; 13– 16 June 2001; Prague, Czech Republic. 2001. FRI0030.
    1. Curtis SP, Bockow B, Fisher C, et al. Etoricoxib in the treatment of osteoarthritis over 52-weeks: a double-blind, active-comparator controlled trial [NCT00242489] BMC Musculoskelet Disord. 2005;6:58.
    1. Curtis SP, Mukhopadhyay S, Ramey D, et al. Cardiovascular safety summary associated with the etoricoxib development program. Arthritis Rheum. 2003b;48(Suppl):S616.
    1. Curtis SP, Ng J, Yu Q, et al. Renal effects of etoricoxib and comparator nonsteroidal antiinflammatory drugs in controlled clinical trials. Clin Ther. 2004;26:70–83.
    1. Cush JJ, Kavanaugh A, Matteson EL. The safety of COX-2 inhibitors. Deliberations from the February 16–18, 2005, FDA meeting [online] Am Coll Rheumatol. 2006 Accessed on 12 January 2006 URL:
    1. Dallob A, Hawkey CJ, Greenberg H, et al. Characterization of etoricoxib, a novel, selective COX-2 inhibitor. J Clin Pharmacol. 2003;43:573–85.
    1. Drazen JM. COX-2 inhibitors — a lesson in unexpected problems. N Engl J Med. 2005;352:1131–2.
    1. [EMEA] European Medicines Agency. Etoricoxib summary of product characteristics [online] 2005a. Accessed 13 January 2006 URL:
    1. [EMEA] European Medicines Agency. Press release: European Medicines Agency concludes action on COX-2 inhibitors [online] 2005b. Accessed 13 January 2006 URL:
    1. Fisher C, Bockow B, Curtis SP, et al. Results of a 190-week randomized study demonstrated similar efficacy of etoricoxib compared with diclofenac in patients with osteoarthritis (OA) [abstract]. Annual Meeting of the European League Against Rheumatism; 18–21 June 2003; Lisbon, Portugal. 2003. FRI0256.
    1. Fisher CA, Curtis SP, Resnick H, et al. Treatment with etoricoxib, a COX-2 selective inhibitor, resulted in clinical improvement in knee and hip osteoarthritis (OA) over 52 weeks [abstract] Arthritis Rheum. 2001;44(Suppl 9):S135. 495.
    1. Fitz Gerald GA. Cardiovascular pharmacology of nonselective nonsteroidal antiinflammatory drugs and coxibs: clinical considerations. Am J Cardiol. 2002;89:26D–32D.
    1. Fitz Gerald GA. Coxibs and cardiovascular disease. N Engl J Med. 2004;351:1709–11.
    1. [FDA] Food and Drug Administration. Consultation NDA 21-042, S-007. Review of cardiovascular safety database: rofecoxib [online] 2001. Accessed 7 July 2005 URL:
    1. [FDA] Food and Drug Administration. COX-2 selective (includes Bextra, Celebrex, and Vioxx) and non-selective non-steroidal antiinflammatory drugs (NSAIDs) [online] 2005a. Accessed 24 February 2006 URL:
    1. [FDA] Food and Drug Administration. COX-2 selective and non-selective non-steroidal antiinflammatory drugs (NSAIDs) [online] 2005b. Accessed 7 July 2005 URL:
    1. [FDA] Food and Drug Administration. FDA presentation: analysis of cardiovascular thromboembolic events with etoricoxib [online] 2005c. Accessed 7 July 2005 URL:
    1. [FDA] Food and Drug Administration. FDA Public Health Advisory: FDA announces important changes and additional warnings for COX-2 selective and non-selective non-steroidal antiinflammatory drugs (NSAIDs) [online] 2005d. Accessed 23 June 2005 URL:
    1. Frizziero L, Graninger W, Langevitz P, et al. Etoricoxib is effective in osteoarthritis patients with different levels of baseline severity of the disease [poster]. Annual European Congress of Rheumatology; 9– 12 June 2004; Berlin, Germany. 2004. FRI0429.
    1. Gossec L, van der HD, Melian A, et al. The efficacy of cyclooxygenase-2 inhibition by etoricoxib and naproxen on the axial manifestations of ankylosing spondylitis in the presence of peripheral arthritis. Ann Rheum Dis. 2005;64:1563–7.
    1. Gottesdiener K, Schnitzer T, Fisher C, et al. Results of a randomized, dose-ranging trial of etoricoxib in patients with osteoarthritis. Rheumatology (Oxford) 2002;41:1052–61.
    1. Hernandez-Garduño A, Vázquez-Leduc A, Querol-Vinagre JV, et al. Clinical evaluation following treatment with etoricoxib (60, 90 and 120mg once a day) in patients with acute low back pain: a cohort, open, non-randomized, multicenter study [abstract]. Annual Meeting of the European League Against Rheumatism; 8–11 June 2005; Vienna, Austria SAT0362. 2005.
    1. Hunsche E, Geling O, Kong SX, et al. Impact of etoricoxib, a novel COX-2 inhibitor, on social and emotional quality of life of patients with osteoarthritis. Osteoporosis Int. 2002;13:S20.
    1. Hunt RH, Harper S, Callegari P, et al. Complementary studies of the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib. Aliment Pharmacol Ther. 2003a;17:201–10.
    1. Hunt RH, Harper S, Watson DJ, et al. The gastrointestinal safety of the COX-2 selective inhibitor etoricoxib assessed by both endoscopy and analysis of upper gastrointestinal events. Am J Gastroenterol. 2003b;98:1725–33.
    1. Jansen JP, Hunsche E, Choy E, et al. Economic evaluation of etoricoxib versus non-selective NSAIDs in the treatment of ankylosing spondylitis in the UK [abstact]. Annual Meeting of the European League Against Rheumatism; 8–11 June 2005; Vienna, Austria. 2005. FRI0475.
    1. Jarrett SJ, Mcgonagle D, Marzo-Ortega H, et al. Etoricoxib reduces the need for biologic therapy in ankylosing spondylitis (AS) but has no effect on magnetic resonance imaging. Results from an open study [abstract]. American College of Rheumatology 68th Annual Scientific Meeting; 16–21 October 2004; San Antonio, TX, USA. 2004. 1634.
    1. Kassahun K, McIntosh IS, Shou M, et al. Role of human liver cytochrome P4503A in the metabolism of etoricoxib, a novel cyclooxygenase-2 selective inhibitor. Drug Metab Dispos. 2001;29:813–20.
    1. Leung AT, Malmstrom K, Gallacher AE, et al. Efficacy and tolerability profile of etoricoxib in patients with osteoarthritis: A randomized, double-blind, placebo and active-comparator controlled 12-week efficacy trial. Curr Med Res Opin. 2002;18:49–58.
    1. Malmstrom K, Ang J, Fricke JR, et al. The analgesic effect of etoricoxib relative to that of two opioid-acetaminophen analgesics: a randomized, controlled single-dose study in acute dental impaction pain. Curr Med Res Opin. 2005;21:141–9.
    1. Malmstrom K, Kotey P, Cichanowitz N, et al. Analgesic efficacy of etoricoxib in primary dysmenorrhea: results of a randomized, controlled trial. Gynecol Obstet Invest. 2003;56:65–9.
    1. Malmstrom K, Kotey P, Coughlin H, et al. A randomized, double-blind, parallel-group study comparing the analgesic effect of etoricoxib to placebo, naproxen sodium, and acetaminophen with codeine using the dental impaction pain model. Clin J Pain. 2004a;20:147–55.
    1. Malmstrom K, Sapre A, Couglin H, et al. Etoricoxib in acute pain associated with dental surgery: a randomized, double-blind, placebo-and active comparator-controlled dose-ranging study. Clin Ther. 2004b;26:667–79.
    1. Martin M, Hunsche E, Boice J, et al. An economic cost analysis of etoricoxib versus indomethacin in the treatment of acute gouty arthritis in the UK [abstract]. Annual Meeting of the European League Against Rheumatism; 8-11 June 2005; Vienna, Austria. 2005. FRI0472.
    1. Matsumoto AK, Collantes E, Melian A, et al. Treatment with etoricoxib resulted in clinical improvement of rheumatoid arthritis (RA) in two randomized active comparator-controlled 52-week trials [abstract]. Annual Meeting of the European League Against Rheumatism; 18–21 June, 2003; Lisbon, Portugal. 2003a. THU0249.
    1. Matsumoto AK, Melian A, Mandel DR, et al. A randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis. J Rheumatol. 2002;29:1623–30.
    1. Matsumoto AK, Zhao PL, Cichanowitz N, et al. Etoricoxib is efficacious in patients with rheumatoid arthritis (RA) on concomitant therapy with disease modifying antirheumatic drugs (DMARDs), and/or low-dose corticosteroids [poster]. American College of Rheumatology 67th Annual Scientific Meeting; 23–28 October 2003; Orlando, FL, USA. 2003b. 209.
    1. Merck Briefing Package for NDA 21-389: Etoricoxib [online] 2005. Accessed 23 June 2005 URL:
    1. Moore A, Phillips C, Hunsche E, et al. Economic evaluation of etoricoxib versus non-selective NSAIDs in the treatment of osteoarthritis and rheumatoid arthritis patients in the UK. Pharmacoeconomics. 2004;22:643–60.
    1. Ouellet M, Riendeau D, Percival MD. A high level of cyclooxygenase-2 inhibitor selectivity is associated with a reduced interference of platelet cyclooxygenase-1 inactivation by aspirin. Proc Natl Acad Sci U S A. 2001;98:14583–8.
    1. Pallay RM, Seger W, Adler JL, et al. Etoricoxib reduced pain and disability and improved quality of life in patients with chronic low back pain: a 3 month, randomized, controlled trial. Scand J Rheumatol. 2004;33:257–66.
    1. Psaty BM, Furberg CD. COX-2 inhibitors — lessons in drug safety. N Engl J Med. 2005;352:1133–5.
    1. Ramey DR, Watson DJ, Yu C, et al. The incidence of upper gastrointestinal adverse events in clinical trials of etoricoxib versus. non-selective NSAIDs: an updated combined analysis. Curr Med Res Opin. 2005;21:715–22.
    1. Ramos-Remus CR, Hunsche E, Mavros P, et al. Evaluation of quality of life following treatment with etoricoxib in patients with arthritis or low-back pain: an open label, uncontrolled pilot study in Mexico. Curr Med Res Opin. 2004;20:691–8.
    1. Rasmussen GL, Bourne MH, Rhondeau SM, et al. Etoricoxib provides pain relief and reduces opioid use in post-orthopedic surgery patients [poster]. Annual European Congress of Rheumatology; 9–12 June 2004; Berlin, Germany. 2004. SAT0130.
    1. Reginster JY, Fischer CL, Beualieu A, et al. Etoricoxib demonstrates similiar efficacy and improved gastrointestinal safety compared with naproxen in two 138-week randomized studies of osteoarthritis patients [abstract]. Annual European Congress of Rheumatology; 9–12 June 2004; Berlin, Germany. 2004. FRI0394.
    1. Riendeau D, Percival MD, Brideau C, et al. Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2. J Pharmacol Exp Ther. 2001;296:558–66.
    1. Rodrigues AD, Halpin RA, Geer LA, et al. Absorption, metabolism, and excretion of etoricoxib, a potent and selective cyclooxygenase-2 inhibitor, in healthy male volunteers. Drug Metab Dispos. 2003;31:224–32.
    1. Rubin BR, Burton R, Navarra S, et al. Efficacy and safety profile of treatment with etoricoxib 120mg once daily compared with indomethacin 50mg three times daily in acute gout: a randomized controlled trial. Arthritis Rheum. 2004;50:598–606.
    1. Schumacher HR, Jr, Boice JA, Daikh DI, et al. Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis. BMJ. 2002;324:1488–92.
    1. Schwartz JI, Greenberg HE, Musser BJ, et al. Inhibition of prostacyclin and thromboxane biosynthesis in healthy volunteers by single and multiple doses of paracetamol (acetaminophen) [poster]. Presented at the Annual European congress of Rheumutalogy; 8–11 June 2005; Vienna, Austria. 2006.
    1. Solomon DH, Karlson EW, Rimm EB, et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation. 2003;107:1303–7.
    1. Solomon SD, McMurray JJ, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005;352:1071–80.
    1. Tacconelli S, Capone ML Sciullimg, et al. The biochemical selectivity of novel COX-2 inhibitors in whole blood assays of COXisozyme activity. Curr Med Res Opin. 2002;18:503–11.
    1. van der Heijde D, Baraf HS, Ramos-Remus C, et al. Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: results of a fifty-two-week, randomized, controlled study. Arthritis Rheum. 2005;52:1205–15.
    1. Wagner JA, Kraft W, Burke J, et al. The COX-2 inhibitor etoricoxib did not alter the anti-platelet of low dose aspirin in health in healthy volunteers [abstract] Arthritis Rheum. 2001;44(Suppl 9):S135. 498.
    1. Warner TD, Mitchell JA. Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. FASEB J. 2004;18:790–804.
    1. Watson DJ, Bolognese JA, Yu C, et al. Use of gastroprotective agents and discontinuations due to dyspepsia with the selective cyclooxygenase-2 inhibitor etoricoxib compared with non-selective NSAIDs. Curr Med Res Opin. 2004;20:1899–908.
    1. Wiesenhutter CW, Boice JA, Ko A, et al. Evaluation of the comparative efficacy of etoricoxib and ibuprofen for treatment of patients with osteoarthritis: A randomized, double-blind, placebo-controlled trial. Mayo Clin Proc. 2005;80:470–9.
    1. [WHO] World Health Organization. World health report 2004 – changing history [online] 2004. Accessed 27 June 2005 URL:
    1. [WHO] World Health Organization. Chronic rheumatic conditions [online] 2005. Accessed 4 March 2005 URL:
    1. Zacher J, Feldman D, Gerli R, et al. A comparison of the therapeutic efficacy and tolerability of etoricoxib and diclofenac in patients with osteoarthritis. Curr Med Res Opin. 2003;19:725–36.
    1. Zerbini C, Ozturk ZE, Grifka J, et al. Efficacy of etoricoxib 60mg/day and diclofenac 150mg/day in reduction of pain and disability in patients with chronic low back pain: results of a 4-week, multinational, randomized, double-blind study. Curr Med Res Opin. 2005;21:2037–49.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe