Advances in Therapy

, Volume 19, Issue 1, pp 27–39

Efficacy of anakinra in bone: Comparison to other biologics

  • Stephen A. Paget
Article

Abstract

Three biologic therapies significantly slow radiographic progression in active rheumatoid arthritis. This paper compares the effects of anakinra, a recombinant human interleukin-1 receptor antagonist, with those of etanercept and infliximab, two drugs that target tumor necrosis factor-alpha. A Medline search identified controlled clinical trials that included radiographic progression as an endpoint. Anakinra 30 to 150 mg subcutaneously each day for 24 weeks was significantly more effective than placebo in slowing progression of erosion, joint-space narrowing, and total composite scores, as assessed by the Genant method, and erosive joint count, as assessed by the Larsen method. Erosion scores were slowed even further during a 24-week extension. Etanercept 25 mg subcutaneously twice weekly and infliximab 3 to 10 mg/kg intravenously every 4 or 8 weeks also slowed progressive joint damage, but these agents were studied under different study designs, patient populations, and radiographic assessments than those used in the anakinra study. Despite these differences, however, each biologic therapy appeared to slow progressive joint damage. In some studies, control of clinical symptoms did not correlate with slowing of radiographic progression. Agents that block interleukin-1 or tumor necrosis factor-alpha appear similarly effective in slowing radiographic progression in patients with active rheumatoid arthritis. Treatment strategies for this disease may need to consider clinical symptoms, progressive joint damage, and long-term safety effects separately.

Keywords

rheumatoid arthritis biologics tumor necrosis factoralpha interleukin-1 

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References

  1. 1.
    Pincus T. Long-term outcomes in rheumatoid arthritis.Br J Rheumatol. 1995;34(suppl 2):59–73.PubMedGoogle Scholar
  2. 2.
    Gough AK, Lilley J, Eyre S, Holder RL, Emery P. Generalised bone loss in patients with early rheumatoid arthritis.Lancet. 1994;344:23–27.PubMedCrossRefGoogle Scholar
  3. 3.
    Celiker R, Gokce-Kutsal Y, Cindas A, et al. Osteoporosis in rheumatoid arthritis: effects of disease activity.Clin Rheumatol. 1995;14:429–433.PubMedCrossRefGoogle Scholar
  4. 4.
    Hooyman JR, Melton LJ, Nelson AM, O’Fallon WM, Riggs BL. Fractures after rheumatoid arthritis. A population-based study.Arthritis Rheum. 1984;27:1353–1361.PubMedCrossRefGoogle Scholar
  5. 5.
    Spector TD, Hall GM, McCloskey EV, Kanis JA. Risk of vertebral fracture in women with rheumatoid arthritis.BMJ. 1993;306:558.PubMedGoogle Scholar
  6. 6.
    Kirwan JR, The effect of glucocorticoids on joint destruction in rheumatoid arthritis.N Engl J Med. 1995;333:142–146.PubMedCrossRefGoogle Scholar
  7. 7.
    Pincus T, Callahan LF, Fuchs HA, Larsen A, Kaye J. Quantitative analysis of hand radiographs in rheumatoid arthritis: time course of radiograpchanges, relation to joint examination measures, and comparison of different scoring methods.J Rheumatol. 1995;22:1983–1989.PubMedGoogle Scholar
  8. 8.
    Fuchs HA, Kaye JJ, Callahan LF, Nance EP, Pincus T. Evidence of significant radiographic damage in rheumatoid arthritis within the first 2 years of disease.J Rheumatol. 1989;16:585–591.PubMedGoogle Scholar
  9. 9.
    McGonagle D, Conaghan PG, O’Connor P, et al. The relationship between synovitis and bone changes in early untreated rheumatoid arthritis: a controlled magnetic resonance imaging study.Arthritis Rheum. 1999;42:1706–1711.PubMedCrossRefGoogle Scholar
  10. 10.
    Klarlund M, Ostergaard M, Jensen KE, Madsen JL, Skjodt H, Lorenzen I. Magnetic resonance imaging, radiography, and scintigraphy of the finger joints: one year follow up of patients with early arthritis.Ann Rheum Dis. 2000;59:521–528.PubMedCrossRefGoogle Scholar
  11. 11.
    Scott DL, Pugner K, Kaarela K, et al. The links between joint damage and disability in rheumatoid arthritis.Rheumatology. 2000;39:122–132.PubMedCrossRefGoogle Scholar
  12. 12.
    Harris ED. Rheumatoid arthritis: pathophysiology and implications for therapy.N Engl J Med. 1990;322:1277–1289.PubMedCrossRefGoogle Scholar
  13. 13.
    Arend WP, Dayer J-M. Inhibition of the production and effects of interleukin-1 and tumor necrosis factor α in rheumatoid arthritis.Arthritis Rheum. 1995;38:151–160.PubMedCrossRefGoogle Scholar
  14. 14.
    Dinarello CA, Wolff SM. The role of interleukin-1 in disease.N Engl J Med. 1993;328:106–113.PubMedCrossRefGoogle Scholar
  15. 15.
    Roux S, Orcel P. Bone loss: factors that regulate osteoclast differentiation: an update.Arthritis Res. 2000;2:451–456.PubMedCrossRefGoogle Scholar
  16. 16.
    Goldring SR, Gravallese EM. Pathogenesis of bone erosions in rheumatoid arthritis.Curr Opin Rheumatol. 2000;12:195–199.PubMedCrossRefGoogle Scholar
  17. 17.
    Burger D, Dayer JM. Inhibitory cytokines and cytokine inhibitors.Neurology. 1995;45(suppl 6): S39-S43.PubMedGoogle Scholar
  18. 18.
    Firestein GS, Boyle DL, Yu C, et al. Synovial interleukin-1 receptor antagonist and interleukin-1 balance in rheumatoid arthritis.Arthritis Rheum. 1994;37:644–652.PubMedCrossRefGoogle Scholar
  19. 19.
    van den Berg W, Joosten LAB, Kollias G, van de Loo F. Role of tumour necrosis factor α in experimental arthritis: separate activity of interleukin 1β in chronicity and cartilage destruction.Ann Rheum Dis. 1999;58(suppl I):I40-I48.PubMedCrossRefGoogle Scholar
  20. 20.
    Horai R, Saijo S, Tanioka H, et al. Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice.J Exp Med. 2000;191: 313–320.PubMedCrossRefGoogle Scholar
  21. 21.
    Bresnihan B, Alvaro-Gracia JM, Cobby M, et al. Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist.Arthritis Rheum. 1998;2196–2204.Google Scholar
  22. 22.
    Moreland LW, Schiff MH, Baumgartner SW, et al. Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial.Ann Intern Med. 1999;130:478–486.PubMedGoogle Scholar
  23. 23.
    Weinblatt ME, Kremer JM, Bankhurst AD, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate.N Engl J Med. 1999;340:253–259.PubMedCrossRefGoogle Scholar
  24. 24.
    Maini R, St Clair EW, Breedveld F, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial.Lancet. 1999;354:1932–1939.PubMedCrossRefGoogle Scholar
  25. 25.
    Larsen A, Dale K, Eek M. Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films.Acta Radiol Diagn. 1977;8:481–491.Google Scholar
  26. 26.
    Sharp JT, Lidsky MD, Collins LS, Moreland J. Methods of scoring the progression of radiologic changes in rheumatoid arthritis: correlation of radiologic, clinical and laboratory abnormalities.Arthritis Rheum. 1971;14:706–720.PubMedCrossRefGoogle Scholar
  27. 27.
    Genant HK, Jiang Y, Peterfy C, Lu Y, Redei J, Countryman PJ. Assessment of rheumatoid arthritis using a modified scoring method on digitized and original radiographs.Arthritis Rheum. 1998; 41:1583–1590.PubMedCrossRefGoogle Scholar
  28. 28.
    van der Heijde DM, van Leeuwen MA, van Riel PL, et al. Biannual radiographic assessment of hands and feet in the three-year prospective followup of patients with early rheumatoid arthritis.Arthritis Rheum. 1992;35:26–34.PubMedCrossRefGoogle Scholar
  29. 29.
    Jiang Y, Genant HK, Watt I, et al. A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: radiologic progression and correlation of Genant and Larsen scores.Arthritis Rheum. 2000;43:1001–1009.PubMedCrossRefGoogle Scholar
  30. 30.
    Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis.N Engl J Med. 2000;343:1586–1593.PubMedCrossRefGoogle Scholar
  31. 31.
    Lipsky PE, van der Heijde DM, St Clair EW, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis.N Engl J Med. 2000;343:1594–1602.PubMedCrossRefGoogle Scholar
  32. 32.
    Safety update on TNF-α antagonist: infliximab and etanercept. Available at: www.fda.gov/ohrms/ dockets/ac/01/briefing/3779b2_01_cber_safety_revision2.htm. Accessed September 4, 2001.Google Scholar
  33. 33.
    Sharp JT, Strand V, Leung H, Hurley F, Loew-Friedrich, for Leflunomide Rheumatoid Arthritis Investigators Group. Treatment with leflunomide slows radiographic progression of rheumatoid arthritis: results from three randomized controlled trials of leflunomide in patients with active rheumatoid arthritis.Arthritis Rheum. 2000;43:495–505.PubMedCrossRefGoogle Scholar

Copyright information

© Health Communications Inc 2002

Authors and Affiliations

  • Stephen A. Paget
    • 1
  1. 1.Department of Rheumatic DiseaseHospital for Special SurgeryNew York

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