Advertisement

European Journal of Clinical Pharmacology

, Volume 70, Issue 9, pp 1021–1027 | Cite as

Impact of biological therapy on spondyloarthritis

  • Nicola Maruotti
  • Francesco Paolo Cantatore
Review Article

Abstract

Purpose

In this review, we focus on the clinical and radiological aspects related to the biological therapy of ankylosing spondylitis (AS), axial spondyloarthritis (SpA) and psoriatic arthritis (PsA).

Methods

A review was carried out in the main medical databases to evaluate the available literature.

Results

Even if there is emerging interest for the role of biological agents other than tumour necrosis factor (TNF)-α inhibitors in spondyloarthritis, anti-TNF-α treatment is currently the only effective therapy for patients in whom conventional therapy with non-steroideal anti-inflammatory drugs (NSAIDs) has failed. Nevertheless, the potential impact of earlier treatment and the best drugs or combinations of drugs for preventing radiographic progression in SpA are yet to be determined.

Conclusions

Anti-TNF-α treatment is currently used with efficacy in the greater part of patients with SpA. In these patients, availability of biological treatment is limited on the bases of potential toxicity and cost. On the basis of clinical trials, biologics other than TNF-α inhibitors can currently not be recommended for the treatment of SpA.

Keywords

Biological Spondylitis Spondyloarthritis TNF-α 

Notes

Conflict of interest

The authors declare that there are no conflict of interest.

References

  1. 1.
    Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A (2002) Ankylosing spondylitis: an overview. Ann Rheum Dis 61(Suppl 3):iii8–18PubMedCentralPubMedGoogle Scholar
  2. 2.
    Khan MA, van der Linden SM (1990) Ankylosing spondylitis and other spondyloarthropathies. Rheum Dis Clin North Am 16:551–579PubMedGoogle Scholar
  3. 3.
    Baraliakos X, Braun J (2011) Spondyloarthritides. Best Pract Res Clin Rheumatol 25(6):825–842PubMedCrossRefGoogle Scholar
  4. 4.
    Braun J, Bollow M, Remlinger G, Eggens U, Rudwaleit M, Distler A, Sieper J (1998) Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum 41(1):58–67PubMedCrossRefGoogle Scholar
  5. 5.
    Saraux A, Guedes C, Allain J, Devauchelle V, Valls I, Lamour A, Guillemin F, Youinou P, Le Goff P (1999) Prevalence of rheumatoid arthritis and spondyloarthropathy in Brittany, France. Société de Rhumatologie de l'Ouest. J Rheumatol 26(12):2622–2627PubMedGoogle Scholar
  6. 6.
    Muche B, Bollow M, François RJ, Sieper J, Hamm B, Braun J (2003) Anatomic structures involved in early- and latestage sacroiliitis in spondylarthritis: a detailed analysis by contrastenhanced magnetic resonance imaging. Arthritis Rheum 48(5):1374–1384PubMedCrossRefGoogle Scholar
  7. 7.
    Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, Braun J, Chou CT, Collantes-Estevez E, Dougados M, Huang F, Gu J, Khan MA, Kirazli Y, Maksymowych WP, Mielants H, Sørensen IJ, Ozgocmen S, Roussou E, Valle-Oñate R, Weber U, Wei J, Sieper J (2009) The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 68(6):777–783PubMedCrossRefGoogle Scholar
  8. 8.
    van der Heijde D, Sieper J, Maksymowych WP, Dougados M, Burgos-Vargas R, Landewé R, Rudwaleit M, Braun J (2011) 2010 Update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis. Ann Rheum Dis 70:905–908PubMedCrossRefGoogle Scholar
  9. 9.
    Azevedo VF, Paiva Edos S, Felippe LR, Moreira RA (2010) Occurrence of fibromyalgia in patients with ankylosing spondylitis. Rev Bras Reumatol 50:646–650PubMedCrossRefGoogle Scholar
  10. 10.
    Landewé R, Braun J, Deodhar A, Dougados M, Maksymowych WP, Mease PJ, Reveille JD, Rudwaleit M, van der Heijde D, Stach C, Hoepken B, Fichtner A, Coteur G, de Longueville M, Sieper J (2014) Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled phase 3 study. Ann Rheum Dis 73(1):39–47PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Song IH et al (2009) Major clinical response of rituximab in active TNFblocker naive patients with ankylosing spondylitis but not in TNFblocker-failure patients - an open label clinical trial. Ann Rheum Dis 68(3):74Google Scholar
  12. 12.
    Nocturne G et al (2009) Lack of efficacy of rituximab in spondylarthropathies: data of 8 patients prospectively followed in the French AIR ("auto-immunity and rituximab") registry. Ann Rheum Dis 68(3):626Google Scholar
  13. 13.
    Berner B et al (2009) Abatacept for therapy of spondyloarthritis due to therapy failure or contraindications of TNF-alpha antagonists. Ann Rheum Dis 68(3):623Google Scholar
  14. 14.
    Haibel H, Rudwaleit M, Listing J, Sieper J (2005) Open label trial of anakinra in active ankylosing spondylitis over 24 weeks. Ann Rheum Dis 64(2):296–298PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Bennett AN, Tan AL, Coates LC, Emery P, Marzo-Ortega H, McGonagle D (2008) Sustained response to anakinra in ankylosing spondylitis. Rheumatology (Oxford) 47(2):223–224CrossRefGoogle Scholar
  16. 16.
    Sieper J, Inman RD, Badalamenti S et al (2012) Sarilumab for the treatment of ankylosing spondylitis: results of a phase 2, randomized. double-blind, placebo-controlled, international study. Ann Rheum Dis 71(Suppl 3):111Google Scholar
  17. 17.
    Sieper J, Porter-Brown B, Thompson L et al (2012) Tocilizumab is not effective for the treatment of ankylosing spondylitis: results of a phase 2, international, multicentre, randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 71(Suppl 3):110Google Scholar
  18. 18.
    Pathan E et al (2011) Efficacy and safety of apremilast, an oral phosphodiesterase inhibitor, in ankylosing spondylitis. Arthritis Rheum 63:W181bGoogle Scholar
  19. 19.
    Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, Gromnica-Ihle E, Kellner H, Krause A, Schneider M, Sörensen H, Zeidler H, Thriene W, Sieper J (2002) Treatment of active ankylosing spondylitis with infliximab: a randomized controlled multicentre trial. Lancet 359(9313):1187–1193PubMedCrossRefGoogle Scholar
  20. 20.
    Baraliakos X, Listing J, Rudwaleit M et al (2007) Safety and efficacy of readministration of infliximab after long-term continuous therapy and withdrawal in patients with ankylosing spondylitis. J Rheumatol 34:510–515PubMedGoogle Scholar
  21. 21.
    Braun J, Baraliakos X, Listing J et al (2008) 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 67:340–345PubMedCrossRefGoogle Scholar
  22. 22.
    Baraliakos X, Listing J, Fritz C, Haibel H, Alten R, Burmester GR, Krause A, Schewe S, Schneider M, Sörensen H, Schmidt R, Sieper J, Braun J (2011) Persistent clinical efficacy and safety of infliximab in ankylosing spondylitis after 8 years—early clinical response predicts long-term outcome. Rheumatology (Oxford) 50(9):1690–2699CrossRefGoogle Scholar
  23. 23.
    Van der Heijde D, Dijkmans B, Geusens P et al (2005) Efficacy and safety of infliximab in patients with ankylosing spondylitis. Results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum 52:582–591PubMedCrossRefGoogle Scholar
  24. 24.
    Heldmann F, Brandt J, Listing J et al (2009) 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, 2009Google Scholar
  25. 25.
    Barkham N, Keen HI, Coates LC, O'Connor P, Hensor E, Fraser AD, Cawkwell LS, Bennett A, McGonagle D, Emery P (2009) Clinical and imaging efficacy of infliximab in HLA-B27-Positive patients with magnetic resonance imaging-determined early sacroiliitis. Arthritis Rheum 60(4):946–954PubMedCrossRefGoogle Scholar
  26. 26.
    Davis JC Jr, Van Der Heijde D, Braun J, Dougados M, Cush J, Clegg DO, Kivitz A, Fleischmann R, Inman R, Tsuji W, Enbrel Ankylosing Spondylitis Study Group (2003) Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum 48(11):3230–3236PubMedCrossRefGoogle Scholar
  27. 27.
    van der Heijde D, Da Silva JC, Dougados M, Geher P, van der Horst-Bruinsma I, Juanola X, Olivieri I, Raeman F, Settas L, Sieper J, Szechinski J, Walker D, Boussuge MP, Wajdula JS, Paolozzi L, Fatenejad S, Etanercept Study 314 Investigators (2006) Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis. Ann Rheum Dis 65(12):1572–1577PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    van der Heijde D, Schiff MH, Sieper J, Kivitz AJ, Wong RL, Kupper H, Dijkmans BA, Mease PJ, Davis JC Jr, ATLAS Study Group (2009) 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 68(6):922–929PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Davis JC Jr, van der Heijde DM, Braun J, Dougados M, Clegg DO, Kivitz AJ, Fleischmann RM, Inman RD, Ni L, Lin SL, Tsuji WH (2008) Efficacy and safety of up to 192 weeks of etanercept therapy in patients with ankylosing spondylitis. Ann Rheum Dis 67(3):346–352PubMedCrossRefGoogle Scholar
  30. 30.
    Brandt J, Khariouzov A, Listing J, Haibel H, Sörensen H, Grassnickel L, Rudwaleit M, Sieper J, Braun J (2003) Six-month results of a double-blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis. Arthritis Rheum 48(6):1667–1675PubMedCrossRefGoogle Scholar
  31. 31.
    Braun J, van der Horst-Bruinsma IE, Huang F, Burgos-Vargas R, Vlahos B, Koenig AS, Freundlich B (2011) Clinical efficacy and safety of etanercept versus sulfasalazine in patients with ankylosing spondylitis: a randomized, double-blind trial. Arthritis Rheum 63(6):1543–51PubMedCrossRefGoogle Scholar
  32. 32.
    Song IH, Weiß A, Hermann KG, Haibel H, Althoff CE, Poddubnyy D, Listing J, Lange E, Freundlich B, Rudwaleit M, Sieper J (2013) Similar response rates in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis after 1 year of treatment with etanercept: results from the ESTHER trial. Ann Rheum Dis 72(6):823–825PubMedCrossRefGoogle Scholar
  33. 33.
    Rudwaleit M, Olivieri I, Boki KA, Griep EN, Järvinen P, Wong RL, Kron M, Kary S, Kupper H (2009) Adalimumab is effective and well tolerated in treating patients with ankylosing spondylitis who have advanced spinal fusion. Rheumatology (Oxford) 48(5):551–557CrossRefGoogle Scholar
  34. 34.
    Haibel H, Rudwaleit M, Listing J, Heldmann F, Wong RL, Kupper H, Braun J, Sieper J (2008) Efficacy of adalimumab in the treatment of axial spondylarthritis 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 58(7):1981–1991PubMedCrossRefGoogle Scholar
  35. 35.
    Sieper J, van der Heijde D, Dougados M et al (2013) Efficacy and safety of adalimumab in patients with nonradiographic axial spondyloarthritis: results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum Dis 72(6):815–822PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Mease P, Sieper J, van den Bosch F, Rahman P, Obermeyer K, Pangan AL (2012) Efficacy and safety of adalimumab in patients with peripheral spondyloarthritis: results from a phase 3 study. Ann Rheum Dis 71:S250CrossRefGoogle Scholar
  37. 37.
    Inman RD, Davis JC Jr, Dv H, Diekman L, Sieper J, Kim SI, Mack M, Han J, Visvanathan S, Xu Z, Hsu B, Beutler A, Braun J (2008) Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum 58(11):3402–3012PubMedCrossRefGoogle Scholar
  38. 38.
    Landewè R, Rudwaleit M, van der Heijde D et al (2012) Effect of certolizumab pegol on signs and symptoms of ankylosing spondylitis and nonradiographic axial spondyloarthritis: 24 week results of a double blind randomized placebocontrolled phase 3 axial spondyloarthritis study. Arthritis Rheum 64(10 Suppl):S336Google Scholar
  39. 39.
    Van der Heijde D, Landewé R, Baraliakos X et al (2008) 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 58:3063–3070PubMedCrossRefGoogle Scholar
  40. 40.
    van der Heijde D, Landewé R, Einstein S, Ory P, Vosse D, Ni L, Lin SL, Tsuji W, Davis JC Jr (2008) Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 58(5):1324–1331PubMedCrossRefGoogle Scholar
  41. 41.
    Van der Heijde D, Salonen D, Weissman BN et al (2009) Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther 11:R127PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Baraliakos X, Listing J, Brandt J et al (2007) Radiographic progression in patients with ankylosing spondylitis after 4 years of treatment with the TNF-alpha antibody infliximab. Rheumatology 46:1450–1453PubMedCrossRefGoogle Scholar
  43. 43.
    Baraliakos X, Listing J, Rudwaleit M, Sieper J, Braun J (2008) The relationship between inflammation and new bone formation in patients with ankylosing spondylitis. Arthritis Res Ther 10(5):R104PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Baraliakos X, Listing J, Rudwaleit M, Brandt J, Sieper J, Braun J (2005) Radiographic progression in patients with ankylosing spondylitis after 2 years of treatment with the tumour necrosis factor alpha antibody infliximab. Ann Rheum Dis 64(10):1462–1466PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Braun J, Baraliakos X, Golder W, Brandt J, Rudwaleit M, Listing J, Bollow M, Sieper J, Van Der Heijde D (2003) Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis, before and after successful therapy with infliximab: evaluation of a new scoring system. Arthritis Rheum 48(4):1126–1136PubMedCrossRefGoogle Scholar
  46. 46.
    Rudwaleit M et al (2004) Magnetic resonance imaging (MRI) of the spine and the sacroiliac joints (SIJ) in ankylosing spondylitis (AS) before and during therapy with the anti-TNF agent etanercept. Arthritis Rheum 50(9):S612Google Scholar
  47. 47.
    Baraliakos X, Davis J, Tsuji W, Braun J (2005) Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis before and after therapy with the tumor necrosis factor alpha receptor fusion protein etanercept. Arthritis Rheum 52(4):1216–1223PubMedCrossRefGoogle Scholar
  48. 48.
    Song IH, Hermann K, Haibel H, Althoff CE, Listing J, Burmester G, Krause A, Bohl-Bühler M, Freundlich B, Rudwaleit M, Sieper J (2011) Effects of etanercept versus sulfasalazine in early axial spondyloarthritis on active inflammatory lesions as detected by whole-body MRI (ESTHER): a 48-week randomised controlled trial. Ann Rheum Dis 70(4):590–596PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Haroon N, Inman R, Learch T et al (2012) Anti-TNF therapy slows radiographic progression of ankylosing spondylitis. Arthritis Rheum 64(10 Suppl):S339Google Scholar
  50. 50.
    Haroon N, Inman RD, Learch TJ, Weisman MH, Lee M, Rahbar MH, Ward MM, Reveille JD, Gensler LS (2013) The impact of tumor necrosis factor α inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum 65(10):2645–2654PubMedCentralPubMedGoogle Scholar
  51. 51.
    Haibel H, Rios V, Hermann KG et al (2009) 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, 2009Google Scholar
  52. 52.
    Song IH, Heldmann F, Rudwaleit M et al (2011) Treatment of active ankylosing spondylitis with abatacept: an open-label, 24-week pilot study. Ann Rheum Dis 70:1108–1110PubMedCrossRefGoogle Scholar
  53. 53.
    Song IH, Heldmann F, Rudwaleit M, Listing J, Appel H, Braun J, Sieper J (2010) Different response to rituximab in tumor necrosis factor blocker-naive patients with active ankylosing spondylitis and in patients in whom tumor necrosis factor blockers have failed: a twenty-four-week clinical trial. Arthritis Rheum 62(5):1290–1297PubMedCrossRefGoogle Scholar
  54. 54.
    Lekpa FK, Farrenq V, Canouΐ-Poitrine F et al (2012) Lack of efficacy of abatacept in axial spondylarthropathies refractory to tumor-necrosis-factor inhibition. Joint Bone Spine 79:47–50PubMedCrossRefGoogle Scholar
  55. 55.
    Wendling D, Dougados M, Berenbaum F et al (2012) A nationwide series: data from the AIR Registry of the French Society of Rheumatology. J Rheumatol 39:2327–2331PubMedCrossRefGoogle Scholar
  56. 56.
    Brulhart L, Nissen MJ, Chevallier P, Gabay C (2010) Tocilizumab in a patient with ankylosing spondylitis and Crohn’s disease refractory to TNF antagonists. Joint Bone Spine 77:625–626PubMedCrossRefGoogle Scholar
  57. 57.
    Cohen JD, Ferreira R, Jorgensen C (2011) Ankylosing spondylitis refractory to tumor necrosis factor blockade responds to tocilizumab. J Rheumatol 38:1527PubMedCrossRefGoogle Scholar
  58. 58.
    Dudler J, Aubry-Rozier B (2011) Tocilizumab in axial spondylarthropathies: about 18 cases. Ann Rheum Dis 70(Suppl 3):128Google Scholar
  59. 59.
    Lekpa FK, Poulain C, Wendling D et al (2012) Is IL-6 an appropriate target to treat spondyloarthritis patients refractory to anti-TNF therapy? a multicentre retrospective observational study. Arthritis Res Ther 14:R53PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Baeten D, Sieper J, Emery P et al (2011) The anti IL-17 A monoclonal antibody secukinumab (AIN457) showed good safety and efficacy in the treatment of active ankylosing spondylitis. Ann Rheum Dis 70(Suppl 3):127Google Scholar
  61. 61.
    McInnes I, Sieper J, Braun J et al (2011) Antiinterleukin 17A monoclonal antibody secukinumab reduces signs and symptoms of psoriatic arthritis in a 24-week multicenter, double-blind, randomized, placebo-controlled trial. Arthritis Rheum 63(Suppl):S306Google Scholar
  62. 62.
    Ritchlin CT, Gottlieb AB, McInnes IB et al (2012) Ustekinumab in active psoriatic arthritis including patients previously treated with anti-TNF agents: results of a phase 3, multicenter, double-blind, placebo-controlled study. Arthritis Rheum 64(Suppl):S1080Google Scholar
  63. 63.
    Kavanaugh A, McInnes IB, Gottlieb AB et al (2012) Ustekinumab in patient with active psoriatic arthritis: results of the phase 3, multicenter, double-blind, PSUMMIT I study. Arthritis Rheum 64(Suppl):S1083Google Scholar
  64. 64.
    Poddubnyy D, Hermann KG, Callhoff J, Listing J, Sieper J (2014) Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS). Ann Rheum Dis 73:817–823PubMedCrossRefGoogle Scholar
  65. 65.
    Schett G, Wollenhaupt J, Papp K et al (2012) Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 64:3156–3167PubMedCrossRefGoogle Scholar
  66. 66.
    Kavanaugh A, Mease P, Gomez-Reino J et al (2012) Apremilast, an oral phosphodiesterase 4 inhibitor, I patients with psoriatic arthritis: results of a phase 3, randomized, controlled trial. Arthritis Rheum 64:4172–4173CrossRefGoogle Scholar
  67. 67.
    Pathan E, Abraham S, Van Rossen E, Withrington R, Keat A, Charles PJ, Paterson E, Chowdhury M, McClinton C, Taylor PC (2013) Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in ankylosing spondylitis. Ann Rheum Dis 72(9):1475–80PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Rheumatology Clinic “Mario Carrozzo”, Department of Medical and Surgical SciencesUniversity of Foggia Medical School, “D’Avanzo” Hospital, Viale degli Aviatori 1FoggiaItaly

Personalised recommendations