Management – medikamentöse und nicht-medikamentöse Therapie der axialen Spondyloarthritis

Zusammenfassung

Der Begriff axiale Spondyloarthritis umfasst sowohl Patienten mit schon vorhandenen Röntgenveränderungen in den Sakroiliakalgelenken oder der Wirbelsäule als auch Patienten in der früheren rein entzündlichen Phase ohne strukturelle Knochenveränderungen. Die Grundlagen der Therapie sind physikalische Therapie und nicht-steroidale Antirheumatika, konventionelle DMARDs spielen im therapeutischen Vorgehen keine Rolle. Die klinische Krankheitsaktivität wird gemessen mit zusammengesetzten Scores, dem BASDAI und dem ASDAS, wobei letzterer außer ‚patient reported outcome‘ – Parametern auch das CRP enthält. Sind Patienten weiterhin aktiv trotz konventioneller Therapie, kommen Biologika zum Einsatz, TNF-Blocker oder IL-17-Inhibitoren. Im Gegensatz zu anderen chronisch-entzündlichen Erkrankungen haben sich andere bisher getestete Biologika als ineffektiv erwiesen, JAK-Inhibitoren könnten eine weitere Therapiemöglichkeit für die Zukunft darstellen. Zur Zeit lässt sich nicht voraussagen, welche axSpA Patienten auf welches Biologikum besser ansprechen.

Abstract

The term axial spondyloarthritis covers both patients with X-ray changes in the sacroiliac joints or spine and patients in the earlier, purely inflammatory stage without structural changes in the bone. Treatment is based on physical therapy and non-steroidal anti-inflammatory drugs, while conventional DMARDs are not effective for axial manifestations. Clinical disease activity is measured by composite scores such as the BASDAI and the ASDAS, the latter containing the CRP level in addition to patient-reported outcome parameters. If patients are still active despite conventional therapy, there is an indication for biologics such as TNF blockers or Il-17 inhibitors. In contrast to other chronic inflammatory diseases, other tested biologics are ineffective for axial spondyloarthritis. JAK inhibitors might be another treatment option for the future. Currently it is not possible to predict which patient responds to which biologic.

Schlüsselwörter

axiale Spondyloarthritis - Therapie - Biologika - Prädiktoren für Therapieansprechen

Key words

axial spondyloarthritis - treatment - biologics - predictors of treatment response

• Literatur

• 1 Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet 2017; 390: 73-84. doi: 10.1016/S0140-6736(16)31591-4
• 2 Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria?. Arthritis Rheum 2005; 52: 1000-1008
• 3 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: 777-783 ard.2009.108233 [pii]. doi: 10.1136/ard.2009.108233
• 4 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; 76: 978-991. doi: 10.1136/annrheumdis-2016-210770
• 5 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: 323-329 doi: 10.1136/ard.2007.075309
• 6 Amor B, Dougados M, Listrat V. et al. Are classification criteria for spondylarthropathy useful as diagnostic criteria?. Rev Rhum Engl Ed 1995; 62: 10-15
• 7 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: 101-107. doi: 10.1136/annrheumdis-2012-203201
• 8 Song IH, Poddubnyy DA, Rudwaleit M. et al. Benefits and risks of ankylosing spondylitis treatment with nonsteroidal antiinflammatory drugs. Arthritis Rheum 2008; 58: 929-938. doi: 10.1002/art.23275
• 9 Kroon FP, van der Burg LR, Ramiro S. et al. Nonsteroidal Antiinflammatory Drugs for Axial Spondyloarthritis: A Cochrane Review. J Rheumatol 2016; 43: 607-617 doi: 10.3899/jrheum.150721
• 10 Haroon NN, Paterson JM, Li P. et al. Patients With Ankylosing Spondylitis Have Increased Cardiovascular and Cerebrovascular Mortality: A Population-Based Study. Ann Intern Med 2015; 163: 409-416 doi: 10.7326/M14-2470
• 11 Bakland G, Gran JT, Nossent JC. Increased mortality in ankylosing spondylitis is related to disease activity. Ann Rheum Dis 2011; 70: 1921-1925. doi: 10.1136/ard.2011.151191
• 12 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: 243-246 doi: 10.1136/annrheumdis-2012-203055
• 13 Althoff CE, Bollow M, Feist E. et al. CT-guided corticosteroid injection of the sacroiliac joints: quality assurance and standardized prospective evaluation of long-term effectiveness over six months. Clin Rheumatol 2015; 34: 1079-1084 doi: 10.1007/s10067-015-2937-7
• 14 Sieper J, Poddubnyy D. New evidence on the management of spondyloarthritis. Nat Rev Rheumatol 2016; 12: 282-295. doi: 10.1038/nrrheum.2016.42
• 15 Molto A, Gossec L, Meghnathi B. et al. An Assessment in SpondyloArthritis International Society (ASAS)-endorsed definition of clinically important worsening in axial spondyloarthritis based on ASDAS. Ann Rheum Dis 2018; 77: 124-127. doi: 10.1136/annrheumdis-2017-212178
• 16 Braun J, Baraliakos X, Kiltz U. et al. Rheumatologists use different cut offs for disease activity in real life - the experience with Golimumab in ankylosing spondylitis – Subanalysis from the Non-Interventional German GO-NICE study. J Rheumatol 2019;
• 17 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. doi: 10.1002/art.24408
• 18 Deodhar A, Gensler LS, Kay J. et al. A Fifty-Two-Week, Randomized, Placebo-Controlled Trial of Certolizumab Pegol in Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol 2019;
• 19 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 doi: 10.1136/ard.2007.073098
• 20 Poddubnyy D, Sieper J. Mechanism of New Bone Formation in Axial Spondyloarthritis. Curr Rheumatol Rep 2017; 19: 55. doi: 10.1007/s11926-017-0681-5
• 21 Baeten D, Sieper J, Braun J. et al. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med 2015; 373: 2534-2548. doi: 10.1056/NEJMoa1505066
• 22 Sieper J, Deodhar A, Marzo-Ortega H. et al. Secukinumab efficacy in anti-TNF-naive and anti-TNF-experienced subjects with active ankylosing spondylitis: results from the MEASURE 2 Study. Ann Rheum Dis 2017; 76: 571-592. doi: 10.1136/annrheumdis-2016-210023
• 23 Pavelka K, Kivitz A, Dokoupilova E. et al. Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3. Arthritis Res Ther 2017; 19: 285 doi: 10.1186/s13075-017-1490-y
• 24 Braun J, Deodhar A, Landewe R. et al. Impact of baseline C-reactive protein levels on the response to secukinumab in ankylosing spondylitis: 3-year pooled data from two phase III studies. RMD Open 2018; 4: e000749 doi: 10.1136/rmdopen-2018-000749
• 25 Braun J, Baraliakos X, Deodhar A. et al. Secukinumab shows sustained efficacy and low structural progression in ankylosing spondylitis: 4-year results from the MEASURE 1 study. Rheumatology (Oxford) 2018;
• 26 Braun J, Haibel H, de Hooge M. et al. Spinal radiographic progression over 2 years in ankylosing spondylitis patients treated with secukinumab: a historical cohort comparison. Arthritis Res Ther 2019; 21: 142. doi: 10.1186/s13075-019-1911-1
• 27 van der Heijde D, Cheng-Chung Wei J, Dougados M. et al. Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial. Lancet 2018; 392: 2441-2451 doi: 10.1016/S0140-6736(18)31946-9
• 28 Deodhar A, Poddubnyy D, Pacheco-Tena C. et al. Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: 16 Week Results of a Phase 3 Randomized, Double-Blind, Placebo Controlled Trial in Patients with Prior Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors. Arthritis Rheumatol 2018;
• 29 van der Heijde D, Gensler LS, Deodhar A et al. Dual neutralisation of il-17A and il-17F with bimekizumab in patients with active ankylosing spondylitis (AS): 12-week results from a phase 2b, randomised, double-blind, placebo-controlled, dose-ranging study. Ann Rheum Dis 2018; 77: (Suppl 2) 70
• 30 Erdes S, Nasonov E, Kunder E et al. Primary efficacy of netakimab, a novel interleukin-17 inhibitor, in the treatment of active ankylosing spondylitis in adults. Clin Exp Rheumatol. 2019 Apr 16. [Epub ahead of print]
• 31 Hueber W, Sands BE, Lewitzky S. et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 2012; 61: 1693-1700. doi: 10.1136/gutjnl-2011-301668
• 32 Schreiber S, Colombel JF, Feagan BG. et al. Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials. Ann Rheum Dis 2019; 78: 473-479. doi: 10.1136/annrheumdis-2018-214273
• 33 Ranganathan V, Gracey E, Brown MA. et al. Pathogenesis of ankylosing spondylitis - recent advances and future directions. Nat Rev Rheumatol 2017; 13: 359-367. doi: 10.1038/nrrheum.2017.56
• 34 Deodhar A, Gensler LS, Sieper J. et al. Three Multicenter, Randomized, Double-Blind, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Ustekinumab in Axial Spondyloarthritis. Arthritis Rheumatol 2019; 71: 258-270 doi: 10.1002/art.40728
• 35 Baeten D, Ostergaard M, Wei JC. et al. Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study. Ann Rheum Dis 2018; 77: 1295-1302 doi: 10.1136/annrheumdis-2018-213328
• 36 van der Heijde D, Deodhar A, Wei JC. et al. Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis 2017; 76: 1340-1347. doi: 10.1136/annrheumdis-2016-210322
• 37 van der Heijde D, Baraliakos X, Gensler LS. et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial. Lancet 2018; 392: 2378-2387. doi: 10.1016/S0140-6736(18)32463-2
• 38 Poddubnyy D, Sieper J. What is the best treatment target in axial spondyloarthritis: tumour necrosis factor alpha, interleukin 17, or both?. Rheumatology (Oxford) 2017; doi:10.1093/rheumatology/kex361