Clinical Guidelines for the Use of Coxibs in Osteoarthritis (OA) and Rhematoid Arthritis (RA)

Celecoxib and rofecoxib, the first-generation coxibs, both demonstrate efficacy in OA and RA and have been included in the updated ACR recommendations for OA management.(54) Newer entrants to the coxib class, valdecoxib, etoricoxib, and others, will provide further treatment options whose value will be assessed after additional data are available. Simple analgesics, such as acetaminophen, are still recommended as first-choice agents for pharmacologic management of patients with OA.(5) An algorithm for the use of coxibs in patients with OA and RA is shown in Figure 1. The guidelines recommend coxibs as an alternative to nonselective NSAIDs in patients at risk of developing GI toxicity associated with NSAID therapy.(5)

Figure 1. The recommendation to "Switch to COX-2-selective inhibitor" for lack of efficacy and adverse effects of nonselective NSAIDs is based in part on numerous studies that have shown treatment with coxibs to be associated with lower rates of discontinuations, less need for GI (protective) cotherapy, less need for GI procedures, and lower risk of developing perforations, ulcers, and bleeds (PUBs). *Risk factors for serious upper GI complications from traditional NSAIDs include age above 65 years, the need for chronic high-dose NSAID therapy, history of peptic ulcer disease, and concomitant treatment with an anticoagulant or glucocorticoid agent. † Includes discussion of risks and benefits with the patient. (Reprinted from the American Journal of Medicine, vol. 110(3A), P.E. Lipsky, "Recommendations for the clinical use of cyclooxygenase- 2-specific inhibitors," pp 3S-5S, copyright 2001, with permission from Excerpta Medica Inc.(14))

References

1. National Center for Chronic Disease Prevention and Health Promotion. Arthritis: the nation's leading cause of disability. Available at: http://www.cdc.gov/nccdphp/arthritis/index.htm. Accessed July 23, 2001.

2. Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998; 41:778-799.

3. Pelletier JP, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum 2001; 44:1237-1247.

4. Lane NE. Pain management in osteoarthritis: the role of COX-2 inhibitors. J Rheumatol 1997; 24(suppl 49):20-24.

5. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum 2000; 43:1905-1915.

6. Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet 2001; 358:903-911.

7. Lorenz HM. Biological agents: a novel approach to the therapy of rheumatoid arthritis. Expert Opin Investig Drugs 2000; 9:1479-1490.

8. Simon LS, Lanza FL, Lipsky PE, et al. Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. Arthritis Rheum 1998; 41:1591-1602.

9. Clemett D, Goa KL. Celecoxib: a review of its use in osteoarthritis, rheumatoid arthritis and acute pain. Drugs 2000; 59:957-980.

10. FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 2001; 345:433-442.

11. Cannon GW, Caldwell JR, Holt P, et al, for the Rofecoxib Phase III Protocol 035 Study Group. Rofecoxib, a specific inhibitor of cyclooxygenase 2, with clinical efficacy comparable with that of diclofenac sodium: results of a one-year, randomized clinical trial in patients with osteoarthritis of the knee and hip. Arthritis Rheum 2000; 43:978-987.

12. Simon LS, Weaver AL, Graham DY, et al. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial. JAMA 1999; 282:1921-1928.

13. Truitt KE, Sperling RS, Ettinger WH Jr, et al, for the Phase III Rofecoxib Geriatric Study Group. A multicenter, randomized, controlled trial to evaluate the safety profile, tolerability, and efficacy of rofecoxib in advanced elderly patients with osteoarthritis. Aging (Milano) 2001; 13:112-121.

14. Lipsky PE. Recommendations for the clinical use of cyclooxygenase- 2-specific inhibitors. Am J Med 2001; 110(3A):3S-5S.

15. Schnitzer TJ, Truitt K, Fleischmann R, et al, for the Phase III Rofecoxib Rheumatoid Arthritis Study Group. The safety profile, tolerability, and effective dose range of rofecoxib in the treatment of rheumatoid arthritis. Clin Ther 1999; 21:1688-1702.

16. Kujubu DA, Fletcher BS, Varnum BC, Lim RW, Herschman HR. TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem 1991; 266:12866-12872.

17. Seibert K, Zhang Y, Leahy K, et al. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci USA 1994; 91:12013-12017.

18. Bellamy N. Outcome measurement in osteoarthritis clinical trials. J Rheumatol 1995; 22(suppl 43):49-51.

19. Bellamy N, Kirwan J, Boers M, et al. Recommendations for a core set of outcome measurement for future Phase III clinical trials in knee, hip, and hand osteoarthritis. Consensus development at OMERACT III. J Rheumatol 1997; 24:799-802.

20. Bellamy N, Campbell J, Syrotuik J. Comparative study of selfrating pain scales in osteoarthritis patients. J Curr Med Res Opin 1999; 15:113-119.

21. Stucki G, Sangha O, Stucki S, et al. Comparison of the WOMAC (Western Ontario and McMaster Universities) osteoarthritis index and a self-report format of the self-administered Lequesne-Algofunctional index in patients with knee and hip osteoarthritis. Osteoarthritis Cartilage 1998; 6:79-86.

22. Steultjens MPM, Roorda LD, Dekker J, Bijlsma JWJ. Responsiveness of observational and self-report methods for assessing disability in mobility in patients with osteoarthritis. Arthritis Care Res 2001; 45:56-61.

23. McConnell S, Kolopack P, Davis AM. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC): a review of its utility and measurement properties. Arthritis Care Res 2001; 45:453-461.

24. Ehrich EW, Davies GM, Watson DJ, Bolognese JA, Seidenberg BC, Bellamy N. Minimal perceptible clinical improvement with the Western Ontario and McMaster Universities osteoarthritis index questionnaire and global assessments in patients with osteoarthritis. J Rheumatol 2000; 27:2635-2641.

25. Bellamy N, Kaloni S, Pope J, Coulter K, Campbell J. Quantitative rheumatology: a survey of outcome measurement procedures in routine rheumatology outpatient practice in Canada. J Rheumatol 1998; 25:852-858.

26. Williams GW, Hubbard RC, Yu SS, Zhao W, Geis GS. Comparison of once-daily and twice-daily administration of celecoxib for the treatment of osteoarthritis of the knee. Clin Ther 2001; 23:213-227.

27. Lequesne MG. The algofunctional indices for hip and knee osteoarthritis. J Rheumatol 1997; 24:779-781.

28. Felson DT, Anderson JJ, Boers M, et al. American College of Rheumatology primary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995; 38:727-735.

29. Scott-Lennox JA, McLaughlin-Miley C, Lennox RD, et al. Stratification of flare intensity identifies placebo responders in a treatment efficacy trial of patients with osteoarthritis. Arthritis Rheum 2001; 44:1599-1607.

30. Saag K, van der Heijde D, Fisher C, et al, for the Osteoarthritis Studies Group. Rofecoxib, a new cyclooxygenase 2 inhibitor, shows sustained efficacy, comparable with other nonsteroidal anti-inflammatory drugs: a 6-week and a 1-year trial in patients with osteoarthritis. Arch Fam Med 2000; 9:1124-1134.

31. Emery P, Zeidler H, Kvien TK, et al. Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison. Lancet 1999; 354:2106-2111.

32. Curtis SP, Fisher C, Kafka S, et al. Treatment with etoricoxib (MK-0663), a COX-2 selective inhibitor, resulted in clinical improvement in knee osteoarthritis (OA) over 52 weeks [abstract SAT0064]. Presented at European League Against Rheumatism (EULAR); June 13-16, 2001; Prague, Czech Republic.

33. 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 495]. Presented at European League Against Rheumatism (EULAR); June 13-16, 2001; Prague, Czech Republic.

34. Bensen WG, Fiechtner JJ, McMillen JI, et al. Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial. Mayo Clin Proc 1999; 74:1095-1105.

35. McKenna F, Borenstein D, Wendt H, Wallemark C, Lefkowith JB, Geis GS. Celecoxib versus diclofenac in the management of osteoarthritis of the knee. Scand J Rheumatol 2001; 30:11-18.

36. Singh G, Goldstein J, Fort J, Bello A, Boots S. SUCCESS-1 in osteoarthritis: celecoxib demonstrates similar efficacy to the conventional NSAIDs, diclofenac and naproxen, in patients with osteoarthritis treated in 39 countries in 6 continents [abstract SAT0093]. Presented at European League Against Rheumatism (EULAR); June 13-16, 2001; Prague, Czech Republic.

37. Ehrich EW, Schnitzer TJ, McIlwain H, et al, for the Rofecoxib Osteoarthritis Pilot Study Group. Effect of specific COX-2 inhibition in osteoarthritis of the knee: a 6 week double blind, placebo controlled pilot study of rofecoxib. J Rheumatol 1999; 26:2438-2447.

38. Cannon GW, Breedveld FC. Efficacy of cyclooxygenase-2-specific inhibitors. Am J Med 2001; 110:6S-12S.

39. Ehrich E, Schnitzer T, Kivitz A, et al. MK-966, a highly selective COX-2 inhibitor, was effective in the treatment of osteoarthritis (OA) of the knee and hip in a 6-week placebo controlled study [abstract 330]. Arthritis Rheum 1997; 40(suppl):S85.

40. Day R, Morrison B, Luza A, et al, for the Rofecoxib/Ibuprofen Comparator Study Group. A randomized trial of the efficacy and tolerability of the COX-2 inhibitor rofecoxib vs ibuprofen in patients with osteoarthritis. Arch Intern Med 2000; 160:1781-1787.

41. Geba GP, Polis AB, Dixon ME, et al. Rofecoxib results in superior clinical response compared to nabumetone in the treatment of osteoarthritis [abstract 440]. Arthritis Rheum 1999; 42(suppl):S144.

42. Geba GP, Weaver AL, Polis AB, et al. Efficacy of rofecoxib, celecoxib, and acetaminophen in osteoarthritis of the knee. JAMA 2002; 287:64-71.

43. Schnitzer TJ, Kivitz AJ, Greenwald M, et al. Rofecoxib provides superior relief of symptoms of osteoarthritis (OA) compared to celecoxib [abstract SAT0089]. Presented at European League Against Rheumatism (EULAR); June 13-16, 2001; Prague, Czech Republic.

44. McKenna F, Weaver A, Fiechtner JJ, Bello AE, Fort JG. COX- 2 specific inhibitors in the management of osteoarthritis of the knee: a placebo-controlled, randomized, double-blind study. J Clin Rheumatol 2001; 7:151-159.

45. Matheson AJ, Figgitt DP. Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis. Drugs 2001; 61:833-865.

46. Eskiyurt N. The first experience of the efficacy and safety of COXIBs in Turkish nation [abstract AB0141]. Presented at European League Against Rheumatism (EULAR); June 13-16, 2001; Prague, Czech Republic.

47. Fiechtner JJ, Sikes D, Recker D. A double-blind, placebo-controlled dose ranging study to evaluate the efficacy of valdecoxib, a novel COX-2 specific inhibitor, in treating the signs and symptoms of osteoarthritis of the knee [abstract OP0048]. Presented at European League Against Rheumatism (EULAR); June 13-16, 2001; Prague, Czech Republic.

48. Schnitzer TJ, Geusens P, Hasier P, et al. Efficacy and safety of COX189 in osteoarthritis: a multi-national study [abstract 1616]. Arthritis Rheum 2001; 44(suppl):S336.

49. Truitt K, Guessens PP, DeTora L, Zhao P. Results of a pivotal (phase III) placebo and active comparator controlled efficacy trial of rofecoxib 25 and 50 mg in adult patients with rheumatoid arthritis (RA) [FR1003]. Presented at European League Against Rheumatism (EULAR); June 13-16, 2001; Prague, Czech Republic.

50. Truitt KE, Lee M, DeTora LM, Anderson M, Zhao P-L. Results of a pivotal (phase III) placebo and active comparator controlled efficacy trial of rofecoxib 12.5 and 25 mg in adult patients with rheumatoid arthritis (RA) [abstract 1897]. Available at: http://www.abstracts-on-line.com/abstracts/ACR/ windowview.asp. Accessed December 20, 2001.

51. Bensen W, Weaver A, Espinoza L, et al. Valdecoxib, a new COX-2 specific inhibitor, is effective in treating the signs and symptoms of rheumatoid arthritis [abstract 1896]. American College of Rheumatology. Available at: http://www.abstracts-online. com/abstracts/ACR/windowview.asp?abst=:;?@&search=.

52. 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 FRI0030]. Presented at European League Against Rheumatism (EULAR); June 13-16, 2001; Prague, Czech Republic.

53. Melian A, Curtis S, Matsumoto A, et al. Etoricoxib in the treatment of rheumatoid arthritis: a 12-week, placebo-controlled and active-comparator, double-blind U.S. study [abstract LB-7]. Available at: http://www.abstracts-on-line.com/abstracts/ACR/ windowview.asp?abs=B99<>&search. Accessed December 20, 2001.

54. Wave of new therapies pushes ACR to revise osteoarthritis guidelines. Geriatrics 2000; 55:25.

Schnitzer TJ, Hochberg MC. COX-2-selective inhibitors in the treatment of arthritis. Cleve Clin J Med 2002;69:SI20-30.