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DOI: 10.1055/s-0037-1618415
Aktueller Stand der Therapie der axialen Spondyloarthritis mit biologischen DMARDs
Current status of biological DMARD therapies in axial spondyloarthritisPublication History
Publication Date:
27 December 2017 (online)
Zusammenfassung
Innerhalb der vergangenen Jahre konnten eindeutige Ziele für die Therapie der axSpA definiert werden. Einerseits sind die Verrin gerung der Krankheitsaktivität sowie andererseits die Verhinderung struktureller Schäden als Therapieziele in den Fokus gerückt. NSAR bilden, immer in Kombination mit nichtmedikamentösen Maßnahmen, das Gerüst der grundlegenden Therapiestrategie. Sollten sich diese als nicht ausreichend wirksam zeigen, kommt im Verlauf der Einsatz sogenannter Biologika (bDMARDs) in Frage. Derzeit sind für die Übergruppe der axSpA fünf TNF-Blocker sowie ein Antikörper gegen Interleukin (IL)-17A zugelassen, wobei einer der TNF-Blocker (Infliximab) sowie der IL-17A-Blocker Secukinumab derzeit nur für die röntgenologische Form (ankylosierende Spondylitis – AS) der axSpA die Zulas-sung besitzen. Die Erkrankungsgruppe der SpA stellt aktuell ein „Hot Topic” in der Untersuchung neuer Therapien in der Rheumatologie dar und es werden in näherer Zukunft neue zugelassene Therapiemechanismen erwartet. Der Stellenwert sowie der optimale Zeitpunkt des Einsatzes neuer „mode of actions” im Therapiealgorithmus der axSpA werden sich in der Zukunft herauskristallisieren müssen.
Summary
In the last years, major targets in the treatment of axSpA could be defined: 1) reduction of active inflammation and 2) prevention or retardation of structural damage. NSAIDs in combination with non-pharmacological procedures are the first-line therapy. If this standard treatment fails, therapy with bDMARDs should be considered. Currently there are five TNF-inhibitors and one monoclonal antibody against IL-17A available in Europe for the treatment of axSpA, while up to date infliximab as one of the TNF-inhibitors and Secukinumab as the anti-IL-17A antibody have the approval only for the radiographic form (AS) of axSpA. SpA is currently a “hot-topic” in clinical trials in the field of rheumatology and new therapeutic options are in the pipeline and will be available in the nearer future. The exact role of new therapies in the treatment algorithm in axSpA still has to be defined.
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Literatur
- 1 Sieper J., Poddubnyy D.. Axial spondyloarthritis. Lancet. 2017 DOI: 10.1016/S0140-6736(16)31591-4
- 2 Rudwaleit M, van der Heijde D, Landewe R. et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009; 68 (06) 777-783.
- 3 de Winter JJ, van Mens LJ, van der Heijde D. et al. Prevalence of peripheral and extra-articular disease in ankylosing spondylitis versus non-radiographic axial spondyloarthritis: a meta-analysis. Arthritis Res Ther 2016; 18: 196
- 4 Dougados M, Baeten D. Spondyloarthritis. Lancet 2011; 377 9783 2127-2137.
- 5 Feldtkeller E, Bruckel J, Khan MA. Scientific contributions of ankylosing spondylitis patient advocacy groups. Curr Opin Rheumatol 2000; 12 (04) 239-247.
- 6 Rudwaleit M, van der Heijde D, Landewe R. et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 2011; 70 (01) 25-31.
- 7 Smolen JS, Braun J, Dougados M. et al. Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force. Ann Rheum Dis 2014; 73 (01) 6-16.
- 8 van der Heijde D, Ramiro S, Landewe R. et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 2017
- 9 Dougados M, Gueguen A, Nakache JP. et al. Ankylosing spondylitis: what is the optimum duration of a clinical study? A one year versus a 6 weeks non-steroidal anti-inflammatory drug trial. Rheumatology (Oxford) 1999; 38 (03) 235-244.
- 10 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 (04) 1205-1215.
- 11 Sieper J, Klopsch T, Richter M. et al. Comparison of two different dosages of celecoxib with diclofenac for the treatment of active ankylosing spondylitis: results of a 12-week randomised, double-blind, controlled study. Ann Rheum Dis 2008; 67 (03) 323-329.
- 12 Song IH, Poddubnyy DA, Rudwaleit M, Sieper J. Benefits and risks of ankylosing spondylitis treatment with nonsteroidal antiinflammatory drugs. Arthritis Rheum 2008; 58 (04) 929-938.
- 13 Sieper J, Lenaerts J, Wollenhaupt J. et al. Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, Part 1. Ann Rheum Dis 2014; 73 (01) 101-107.
- 14 Poddubnyy D, Listing J, Sieper J. Brief Report: Course of Active Inflammatory and Fatty Lesions in Patients With Early Axial Spondyloarthritis Treated With Infliximab Plus Naproxen as Compared to Naproxen Alone: Results From the Infliximab As First Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial. Arthritis Rheumatol 2016; 68 (08) 1899-1903.
- 15 Kroon F, Landewe R, Dougados M. et al. Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis. Ann Rheum Dis 2012; 71 (10) 1623-1629.
- 16 Wanders A, Heijde D, Landewe R. et al. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum 2005; 52 (06) 1756-1765.
- 17 Poddubnyy D, Rudwaleit M, Haibel H. et al. Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort. Ann Rheum Dis 2012; 71 (10) 1616-1622.
- 18 Sieper J, Listing J, Poddubnyy D. et al. Effect of continuous versus on-demand treatment of ankylosing spondylitis with diclofenac over 2 years on radiographic progression of the spine: results from a randomised multicentre trial (ENRADAS). Ann Rheum Dis 2016; 75 (08) 1438-1443.
- 19 Haibel H, Brandt HC, Song IH. et al. No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial. Ann Rheum Dis 2007; 66 (03) 419-421.
- 20 Braun J, Zochling J, Baraliakos X. et al. Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial. Ann Rheum Dis 2006; 65 (09) 1147-1153.
- 21 Haibel H, Rudwaleit M, Braun J, Sieper J. Six months open label trial of leflunomide in active ankylosing spondylitis. Ann Rheum Dis 2005; 64 (01) 124-126.
- 22 Haibel H, Fendler C, Listing J. et al. Efficacy of oral prednisolone in active ankylosing spondylitis: results of a double-blind, randomised, placebo-controlled short-term trial. Ann Rheum Dis 2014; 73 (01) 243-246.
- 23 van der Heijde D, Lie E, Kvien TK. et al. ASDAS, a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis. Ann Rheum Dis 2009; 68 (12) 1811-1818.
- 24 Garrett S, Jenkinson T, Kennedy LG. et al. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 1994; 21 (12) 2286-2291.
- 25 Haroon N. The effect of tumor necrosis factor-blockade on new bone formation in ankylosing spondylitis: what is the evidence?. Curr Opin Rheumatol 2014; 26 (04) 389-394.
- 26 Baraliakos X, Haibel H, Listing J. et al. Continuous long-term anti-TNF therapy does not lead to an increase in the rate of new bone formation over 8 years in patients with ankylosing spondylitis. Ann Rheum Dis 2014; 73 (04) 710-715.
- 27 Baeten D, Sieper J, Braun J. et al. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med 2015; 373 (26) 2534-2548.
- 28 Langley RG, Elewski BE, Lebwohl M. et al. Secukinumab in plaque psoriasis--results of two phase 3 trials. N Engl J Med 2014; 371 (04) 326-338.
- 29 McInnes IB, Mease PJ, Kirkham B. et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2015; 386 9999 1137-1146.
- 30 Haibel H, Rudwaleit M, Listing J, Sieper J. Open label trial of anakinra in active ankylosing spondylitis over 24 weeks. Ann Rheum Dis 2005; 64 (02) 296-298.
- 31 Song IH, Heldmann F, Rudwaleit M. et al. Treatment of active ankylosing spondylitis with abatacept: an open-label, 24-week pilot study. Ann Rheum Dis 2011; 70 (06) 1108-1110.
- 32 Song IH, Heldmann F, Rudwaleit M. et al. 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 2010; 62 (05) 1290-1297.
- 33 Sieper J, Braun J, Kay J. et al. Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN). Ann Rheum Dis 2015; 74 (06) 1051-1057.
- 34 Sieper J, Porter-Brown B, Thompson L. et al. Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials. Ann Rheum Dis 2014; 73 (01) 95-100.
- 35 Sieper J, Poddubnyy D. New evidence on the management of spondyloarthritis. Nat Rev Rheumatol 2016; 12 (05) 282-295.
- 36 Poddubnyy D, Hermann KG, Callhoff J. et al. 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 2014; 73 (05) 817-823.
- 37 Pathan E, Abraham S, Van Rossen E. et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in ankylosing spondylitis. Ann Rheum Dis 2013; 72 (09) 1475-1480.
- 38 http://ir.celgene.com/releasedetail.cfm?releaseid= 858785 last accessed on 06.02.2017.
- 39 van der Heijde D, Deodhar A, Wei J. et al. Tofacitinib in patients with ankylosing spondylitis: a phase 2, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis 2016; 75 (Suppl. 02) 52