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Update on Biologic Therapy in the Management of Axial Spondyloarthritis

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Abstract

Axial spondyloarthritis, which includes ankylosing spondylitis and psoriatic spondyloarthritis, is an important subtype of the spondyloarthritides. Tumor necrosis factor (TNF) antagonists are effective therapies for this partially heterogeneous group of rheumatic diseases in terms of signs, symptoms, and functioning, but they do not seem to substantially inhibit radiographic progression, which is mainly new bone formation in ankylosing spondylitis. However, they clearly reduce inflammation, as shown by MRI. TNF blockers are also efficacious in the treatment of extraspinal features of spondyloarthritis. In addition, evidence indicates that anti-TNF therapy works well in early axial disease. Other biologics are currently being investigated, as alternatives are needed for patients who fail anti-TNF therapy.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Braun J, Sieper J: Biological therapies in the spondyloarthritides—the current state. Rheumatology 2004, 43:1072–1084.

    Article  CAS  PubMed  Google Scholar 

  2. Braun J, Sieper J: Ankylosing spondylitis. Lancet 2007, 369:1379–1390.

    Article  PubMed  Google Scholar 

  3. Saraux A, Guedes C, Allain J, et al.: Prevalence of rheumatoid arthritis and spondyloarthropathy in Brittany, France. Societe de Rhumatologie de l’Ouest. J Rheumatol 1999, 26:2622–2627.

    CAS  PubMed  Google Scholar 

  4. Van der Linden S, Valkenburg HA, Cats A: Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984, 27:361–368.

    Article  PubMed  Google Scholar 

  5. •• Sieper J, Rudwaleit M, Baraliakos X, et al.: The Assessment of SpondyloArthritis International Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis 2009, 68(Suppl 2):ii1–ii44. These new criteria for SpA will help us treat even early stages of the disease adequately.

    Article  PubMed  Google Scholar 

  6. Zochling J, van der Heijde D, Burgos-Vargas R, et al.: ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2006, 65:442–452.

    Article  CAS  PubMed  Google Scholar 

  7. Braun J, Pham T, Sieper J, et al.: International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis 2003, 62:817–824.

    Article  CAS  PubMed  Google Scholar 

  8. Braun J, Davis J, Dougados M, et al.: First update of the international ASAS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis. Ann Rheum Dis 2006, 65:316–320.

    Article  CAS  PubMed  Google Scholar 

  9. Braun J, Bollow M, Neure L, et al.: Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum 1995, 38:499–505.

    Article  CAS  PubMed  Google Scholar 

  10. Brandt J, Haibel H, Cornely D, et al.: Successful treatment of active ankylosing spondylitis with the anti-tumour necrosis factor alpha monoclonal antibody infliximab. Arthritis Rheum 2000, 43:1346–1352.

    Article  CAS  PubMed  Google Scholar 

  11. Brandt J, Haibel H, Reddig J, et al.: Treatment of patients with severe ankylosing spondylitis with infliximab—a one year follow up. Arthritis Rheum 2001, 44:2936–2937.

    Article  CAS  PubMed  Google Scholar 

  12. Braun J, Brandt J, Listing J, et al.: Treatment of active ankylosing spondylitis with infliximab—a double-blind placebo controlled multicenter trial. Lancet 2002, 359:1187–1193.

    Article  CAS  PubMed  Google Scholar 

  13. Van der Heijde D, Dijkmans B, Geusens P, et al.: Efficacy and safety of infliximab in patients with ankylosing spondylitis. Results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum 2005, 52:582–591.

    Article  PubMed  Google Scholar 

  14. Nikas SN, Alamanos Y, Voulgari PV, et al.: Infliximab treatment in ankylosing spondylitis: an observational study. Ann Rheum Dis 2005, 64:940–942.

    Article  CAS  PubMed  Google Scholar 

  15. Keeling S, Oswald A, Russell AS, Maksymovych WP: Prospective observational analysis of the efficacy and safety of low-dose (3 mg/kg) infliximab in ankylosing spondylitis: 4-year follow-up. J Rheumatol 2006, 33:558–561.

    CAS  PubMed  Google Scholar 

  16. Jois RN, Leeder J, Gibb A, et al.: Low-dose infliximab treatment for ankylosing spondylitis—clinically- and cost-effective. Rheumatology 2006, 45:1566–1569.

    Article  CAS  PubMed  Google Scholar 

  17. Sidiropoulos P, Kritikos HD, Siakka P, et al.: Low dose of infliximab is inadequate in most patients with spondyloarthropathies. Clin Exp Rheumatol 2005, 23:513–516.

    CAS  PubMed  Google Scholar 

  18. Inman RD, Maksymowych WP: A double-blind, placebo-controlled trial of low-dose infliximab in ankylosing spondylitis. J Rheumatol 2010, 37:1203–1210.

    Article  PubMed  Google Scholar 

  19. Braun J, Deodhar A, Dijkmans B, et al.: Efficacy and safety of infliximab in patients with ankylosing spondylitis over a two-year period. Arthritis Rheum 2008, 59:1270–1278.

    Article  CAS  PubMed  Google Scholar 

  20. Heldmann F, Brandt J, Listing J, et al.: European Ankylosing Spondylitis Infliximab Cohort (EASIC): long term efficacy of infliximab in patients with ankylosing spondylitis (AS) after 2 years of EASIC. Presented at the Annual Meeting of the European League Against Rheumatism. Copenhagen, Denmark; June 10–13, 2009.

  21. Baraliakos X, Listing J, Rudwaleit M, et al.: Safety and efficacy of readministration of infliximab after long-term continuous therapy and withdrawal in patients with ankylosing spondylitis. J Rheumatol 2007, 34:510–515.

    CAS  PubMed  Google Scholar 

  22. Braun J, Baraliakos X, Listing J, et al.: Persistent clinical efficacy and safety of anti-tumour necrosis factor alpha therapy with infliximab in patients with ankylosing spondylitis over 5 years: evidence for different types of response. Ann Rheum Dis 2008, 67:340–345.

    Article  CAS  PubMed  Google Scholar 

  23. Breban M, Ravaud P, Claudepierre P, et al.: Maintenance of infliximab treatment in ankylosing spondylitis: results of a one-year randomized controlled trial comparing systematic versus on-demand treatment. Arthritis Rheum 2008, 58:88–97.

    Article  CAS  PubMed  Google Scholar 

  24. Li EK, Griffith JF, Lee VW, et al.: Short-term efficacy of combination methotrexate and infliximab in patients with ankylosing spondylitis: a clinical and magnetic resonance imaging correlation. Rheumatology 2008, 47:1358–1363.

    Article  CAS  PubMed  Google Scholar 

  25. Davis JC Jr, van der Heijde D, Braun J, et al.: Efficacy and safety of up to 192 weeks of etanercept therapy in patients with ankylosing spondylitis. Ann Rheum Dis 2008, 67:346–352.

    Article  CAS  PubMed  Google Scholar 

  26. Brandt J, Khariouzov A, Listing J, et al.: Six months results of a German double-blind placebo controlled, phase III clinical trial of etanercept in active ankylosing spondylitis. Arthritis Rheum 2003, 48:1667–1675.

    Article  CAS  PubMed  Google Scholar 

  27. Brandt J, Listing J, Haibel H, et al.: Long-term efficacy and safety of etanercept after readministration in patients with active ankylosing spondylitis. Rheumatology 2005, 44:342–348.

    Article  CAS  PubMed  Google Scholar 

  28. Van der Heijde D, Da Silva JC, Dougados M, et al.: Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis. Ann Rheum Dis 2006, 65:1572–1577.

    Article  PubMed  Google Scholar 

  29. Van der Heijde D, Schiff MH, Sieper J, et al.: Adalimumab effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long-term results from the ATLAS trial. Ann Rheum Dis 2009, 68:922–929.

    Article  PubMed  Google Scholar 

  30. Rudwaleit M, Olivieri I, Boki KA, et al.: Adalimumab is effective and well tolerated in treating patients with ankylosing spondylitis who have advance spinal fusion. Rheumatology 2009, 48:551–557.

    Article  CAS  PubMed  Google Scholar 

  31. Inman RD, Davis JC Jr, van der Heijde D, et al.: Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo controlled, phase III trial. Arthritis Rheum 2008, 58:3402–3412.

    Article  CAS  PubMed  Google Scholar 

  32. Baraliakos X, Listing J, Rudwaleit M, et al.: The relationship between inflammation and new bone formation in patients with ankylosing spondylitis. Arthritis Res Ther 2008, 10:R104.

    Article  PubMed  Google Scholar 

  33. Van der Heijde D, Landewé R, Einstein S, et al.: Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 2008, 58:1324–1331.

    Article  PubMed  Google Scholar 

  34. Van der Heijde D, Landewé R, Baraliakos X, et al.; Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy Study Group: Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum 2008, 58:3063–3070.

    Article  PubMed  Google Scholar 

  35. Van der Heijde D, Salonen D, Weissman BN, et al.: Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther 2009, 11:R127.

    Article  PubMed  Google Scholar 

  36. Baraliakos X, Heldmann F, van der Heijde D, et al.: Radiographic findings after 5 years of infliximab treatment in patients with ankylosing spondylitis. Presented at the Annual Meeting of the European League Against Rheumatism. Rome, Italy; June 16–19, 2010.

  37. Baraliakos X, Listing J, Rudwaleit M, et al.: Progression of radiographic damage in patients with ankylosing spondylitis: defining the central role of syndesmophytes. Ann Rheum Dis 2007, 66:910–915.

    Article  CAS  PubMed  Google Scholar 

  38. • Baraliakos X, Listing J, Rudwaleit M, et al.: Development of a radiographic scoring tool for ankylosing spondylitis only based on bone formation: addition of the thoracic spine improves sensitivity to change. Arthritis Rheum 2009, 61:764–771. Involvement of the thoracic spine, which is often affected by inflammation in AS, in a scoring tool for radiographic progression provides a better sensitivity to change, taking into account that TNF blockers failed to show that they can prevent radiographic progression.

    Article  CAS  PubMed  Google Scholar 

  39. Baraliakos X, Listing J, von der Recke A, Braun J: The natural course of radiographic progression in ankylosing spondylitis—evidence for major individual variations in a large proportion of patients. J Rheumatol 2009, 36:997–1002.

    Article  PubMed  Google Scholar 

  40. Appel H, Ruiz-Heiland G, Listing J, et al.: Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum 2009, 60:3257–3262.

    Article  PubMed  Google Scholar 

  41. Baraliakos X, Listing J, Brandt J, et al.: Radiographic progression in patients with ankylosing spondylitis after 4 years of treatment with the TNF-alpha antibody infliximab. Rheumatology 2007, 46:1450–1453.

    Article  CAS  PubMed  Google Scholar 

  42. Braun J, Baraliakos X, Listing J, Sieper J: Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum 2005, 52:2447–2451.

    Article  CAS  PubMed  Google Scholar 

  43. Rudwaleit M, Rodevand E, Holck P, et al.: Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study. Ann Rheum Dis 2009, 68:696–701.

    Article  CAS  PubMed  Google Scholar 

  44. Braun J, Baraliakos X, Listing J, et al.: Differences in the incidence of flares or new onset of inflammatory bowel diseases in patients with ankylosing spondylitis exposed to therapy with anti-tumor necrosis factor alpha agents. Arthritis Rheum 2007, 57:639–647.

    Article  CAS  PubMed  Google Scholar 

  45. Braun J, Rudwaleit M, Kary S, et al.: Clinical manifestations and responsiveness to adalimumab are similar in patients with ankylosing spondylitis with and without concomitant psoriasis. Rheumatology 2010 May 6 (Epub ahead of print).

  46. Rudwaleit M, Schwarzlose S, Hilgert ES, et al.: MRI in predicting a major clinical response to anti-tumour necrosis factor treatment in ankylosing spondylitis. Ann Rheum Dis 2008, 67:1276–1281.

    Article  CAS  PubMed  Google Scholar 

  47. Rudwaleit M, Claudepierre P, Wordsworth P, et al.: Effectiveness, safety, and predictors of good clinical response in 1250 patients treated with adalimumab for active ankylosing spondylitis. J Rheumatol 2009, 36:801–808.

    Article  CAS  PubMed  Google Scholar 

  48. De Vries MK, van Eick IC, van der Horst-Bruinsma IE, et al.: Erythrocyte sedimentation rate, C-reactive protein level, and serum amyloid a protein for patient selection and monitoring of anti-tumor necrosis factor treatment in ankylosing spondylitis. Arthritis Rheum 2009, 61:1484–1490.

    Article  PubMed  Google Scholar 

  49. Zochling J, Braun J: Remission in ankylosing spondylitis. Clin Exp Rheumatol 2006, 24(Suppl 43):S88–S92.

    Google Scholar 

  50. Neidhart M, Baraliakos X, Seemayer C, et al.: Expression of cathepsin K and matrix metalloproteinase 1 indicate persistent osteodestructive activity in long-standing ankylosing spondylitis. Ann Rheum Dis 2009, 68:1334–1339.

    Article  CAS  PubMed  Google Scholar 

  51. De Vries MK, Wolbink GJ, Stapel SO, et al.: Inefficacy of infliximab in ankylosing spondylitis is correlated with antibody formation. Ann Rheum Dis 2007, 66:133–134.

    Article  PubMed  Google Scholar 

  52. De Vries MK, Brouwer E, van der Horst-Bruinsma IE, et al.: Decreased clinical response to adalimumab in ankylosing spondylitis is associated with antibody formation. Ann Rheum Dis 2009, 68:1787–1788.

    Article  PubMed  Google Scholar 

  53. Conti F, Ceccarelli F, Marocchi E, et al.: Switching tumour necrosis factor alpha antagonists in patients with ankylosing spondylitis and psoriatic arthritis: an observational study over a 5-year period. Ann Rheum Dis 2007, 66:1393–1397.

    Article  CAS  PubMed  Google Scholar 

  54. Mau W, Zeidler H, Mau R, et al.: Clinical features and prognosis of patients with possible ankylosing spondylitis. Results of a 10-year follow-up. J Rheumatol 1988, 7:1109–1114.

    Google Scholar 

  55. Brandt J, Haibel H, Reddig J, et al.: Successful short term treatment of severe undifferentiated spondyloarthropathy with the anti-tumor necrosis factor-α monoclonal antibody infliximab. J Rheumatol 2002, 29:118–122.

    CAS  PubMed  Google Scholar 

  56. Brandt J, Khariouzov A, Listing J, et al.: Successful short term treatment of patients with severe undifferentiated spondyloarthritis with the anti-tumor necrosis factor-alpha fusion receptor protein etanercept. J Rheumatol 2004, 31:531–538.

    CAS  PubMed  Google Scholar 

  57. Haibel H, Rudwaleit M, Listing J, et al.: Efficacy of adalimumab in the treatment of axial spondyloarthritis without radiographically defined sacroiliitis: results of a twelve-week randomized, double-blind, placebo-controlled trial followed by an open-label extension up to week fifty-two. Arthritis Rheum 2008, 58:1981–1991.

    Article  CAS  PubMed  Google Scholar 

  58. Amtenbrink AL, Haibel H, Rudwaleit M, et al.: Adalimumab successfully re-treats and maintains long-term efficacy in axial spondyloarthritis (SpA) patients without radiographic sacroiliitis who relapse following adalimumab withdrawal [abstract 1108]. Presented at the Annual Meeting of the American College of Rheumatology. San Francisco, CA; October 24–29, 2008.

  59. Haibel H, Rios V, Hermann KG, et al.: No progression of chronic sacroiliac changes in patients with active, non-radiographic axial spondyloarthritis treated with adalimumab over 52 weeks [abstract 1798]. Presented at the Annual Meeting of the American College of Rheumatology. Philadelphia, PA; October 16–21, 2009.

  60. Barkham N, Keen HI, Coates LC, et al.: Clinical and imaging efficacy of infliximab in HLA B27-positive patients with magnetic resonance imaging-determined early sacroiliitis. Arthritis Rheum 2009, 60:946–954.

    Article  CAS  PubMed  Google Scholar 

  61. Schneeweiss S, Setoguchi S, Weinblatt ME, et al.: Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis. Arthritis Rheum 2007, 56:1754–1764.

    Article  CAS  PubMed  Google Scholar 

  62. Zink A, Askling J, Dixon WG, et al.: European biologicals registers: methodology, selected results, and perspectives. Ann Rheum Dis 2009, 68:1240–1246.

    Article  CAS  PubMed  Google Scholar 

  63. Pallavicini FB, Caporali R, Sarzi-Puttini P, et al.: Tumour necrosis factor antagonist therapy and cancer development: analysis of the LORHEN registry. Autoimmun Rev 2010, 9:175–180.

    Article  PubMed  Google Scholar 

  64. Askling J, Baecklund E, Granath F, et al.: Anti-tumor necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas: relative risks and time trends in the Swedish Biologics register. Ann Rheum Dis 2009, 68:648–653.

    Article  CAS  PubMed  Google Scholar 

  65. Mariette X, Tubach F, Bagheri H, et al.: Lymphoma in patients treated with anti-TNF: results of the 3-year prospective French RATIO registry. Ann Rheum Dis 2010, 69:400–408.

    Article  CAS  PubMed  Google Scholar 

  66. Askling J, Klareskog L, Blomqvist P, et al.: Risk for malignant lymphoma in ankylosing spondylitis: a nationwide Swedish case-control study. Ann Rheum Dis 2006, 65:1184–1187.

    Article  CAS  PubMed  Google Scholar 

  67. Tan AL, Marzo-Ortega H, O’Connor P, et al.: Efficacy of anakinra in active ankylosing spondylitis: a clinical and magnetic resonance imaging study. Ann Rheum Dis 2004, 63:1041–1045.

    Article  CAS  PubMed  Google Scholar 

  68. Haibel H, Rudwaleit M, Listing J, et al.: Open label trial of anakinra in active ankylosing spondylitis over 24 weeks. Ann Rheum Dis 2005, 64:296–298.

    Article  CAS  PubMed  Google Scholar 

  69. Song I, Heldmann F, Rudwaleit M, et al.: Major clinical response of rituximab in active TNF-blocker-naive patients with ankylosing spondylitis but not in TNF-blocker-failure patients-an open label clinical trial. Presented at the Annual Meeting of the European League Against Rheumatism. Copenhagen, Denmark; June 10–13, 2009.

  70. Bal A, Unlu E, Bahar G, et al.: Comparison of serum IL-1 beta, sIL-2R, IL-6, and TNF-alpha levels with disease activity parameters in ankylosing spondylitis. Clin Rheumatol 2007, 26:211–215.

    Article  CAS  PubMed  Google Scholar 

  71. Visvanathan S, Wagner C, Marini JC, et al.: Inflammatory biomarkers, disease activity and spinal disease measures in patients with ankylosing spondylitis after treatment with infliximab. Ann Rheum Dis 2008, 67:511–517.

    Article  CAS  PubMed  Google Scholar 

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Disclosure

Dr. Heldmann has served on a board for UCB; has had research funded by Wyeth and Centocor Ortho Biotech; and has had his travel/accommodation expenses reimbursed by Roche, Wyeth, Pfizer, Abbott Laboratories, Centocor Ortho Biotech, Eli Lilly and Company, Merck Serono, and Novartis.

Dr. Braun has served on boards for, served as a consultant for, received grants from, received payment for development of educational presentations from, and had travel/accommodation expense reimbursed by Centocor Ortho Biotech, Amgen, Abbott Laboratories, Roche, Bristol-Myers Squibb, Novartis, Pfizer, and Merck Sharp & Dohme Idea. No other potential conflicts of interest relevant to this article were reported.

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  1. Rheumazentrum Ruhrgebiet, Landgrafenstrasse 15, 44652, Herne, Germany

    Frank Heldmann, Friedrich Dybowski, Ertan Saracbasi-Zender, Claas Fendler & Jürgen Braun

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  1. Frank Heldmann
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  2. Friedrich Dybowski
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Heldmann, F., Dybowski, F., Saracbasi-Zender, E. et al. Update on Biologic Therapy in the Management of Axial Spondyloarthritis. Curr Rheumatol Rep 12, 325–331 (2010). https://doi.org/10.1007/s11926-010-0125-y

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