Prediction of Treatment Response at 6 Months by Combinatorial Analysis of Serum Biomarkers in Biotherapy Naive SpA

Summary

The main objective of this trial is to search for biomarkers associated with the success of adalimumab treatment in order to generate an algorithm to predict the response to this treatment at 6 months in spondyloarthritis and to define its metrological properties on this cohort. The algorithm will allow to better target patients who will have an important benefit/risk ratio for adalimumab treatment.

Timeline

Start

2018-06-14

Primary completion

2019-12-14

Completion

2020-05-07

Publications

• Background Aaltonen KJ, Virkki LM, Malmivaara A, Konttinen YT, Nordstrom DC, Blom M. Systematic review and meta-analysis of the efficacy and safety of existing TNF blocking agents in treatment of rheumatoid arthritis. PLoS One. 2012;7(1):e30275. doi: 10.1371/journal.pone.0030275. Epub 2012 Jan 17.
• Background Baeten D, Kruithof E, Van den Bosch F, Van den Bossche N, Herssens A, Mielants H, De Keyser F, Veys EM. Systematic safety follow up in a cohort of 107 patients with spondyloarthropathy treated with infliximab: a new perspective on the role of host defence in the pathogenesis of the disease? Ann Rheum Dis. 2003 Sep;62(9):829-34. doi: 10.1136/ard.62.9.829.
• Background Baillet A, Trocme C, Berthier S, Arlotto M, Grange L, Chenau J, Quetant S, Seve M, Berger F, Juvin R, Morel F, Gaudin P. Synovial fluid proteomic fingerprint: S100A8, S100A9 and S100A12 proteins discriminate rheumatoid arthritis from other inflammatory joint diseases. Rheumatology (Oxford). 2010 Apr;49(4):671-82. doi: 10.1093/rheumatology/kep452. Epub 2010 Jan 25.
• Background Brandt J, Khariouzov A, Listing J, Haibel H, Sorensen H, Grassnickel L, Rudwaleit M, Sieper J, Braun J. Six-month results of a double-blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis. Arthritis Rheum. 2003 Jun;48(6):1667-75. doi: 10.1002/art.11017.
• Background Braun J, de Keyser F, Brandt J, Mielants H, Sieper J, Veys E. New treatment options in spondyloarthropathies: increasing evidence for significant efficacy of anti-tumor necrosis factor therapy. Curr Opin Rheumatol. 2001 Jul;13(4):245-9. doi: 10.1097/00002281-200107000-00001.
• Background Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, Gromnica-Ihle E, Kellner H, Krause A, Schneider M, Sorensen H, Zeidler H, Thriene W, Sieper J. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet. 2002 Apr 6;359(9313):1187-93. doi: 10.1016/s0140-6736(02)08215-6.
• Background Braun J, Pham T, Sieper J, Davis J, van der Linden S, Dougados M, van der Heijde D; ASAS Working Group. International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis. 2003 Sep;62(9):817-24. doi: 10.1136/ard.62.9.817.
• Background Braun J, Sieper J. Biological therapies in the spondyloarthritides--the current state. Rheumatology (Oxford). 2004 Sep;43(9):1072-84. doi: 10.1093/rheumatology/keh205. Epub 2004 Jun 8.
• Background Claudepierre P, Wendling D, Breban M, Goupillle P, Dougados M. Ankylosing spondylitis, spondyloarthropathy, spondyloarthritis, or spondylarthritis: what's in a name? Joint Bone Spine. 2012 Dec;79(6):534-5. doi: 10.1016/j.jbspin.2012.06.003. Epub 2012 Jul 28. No abstract available.
• Background Haibel H, Rudwaleit M, Brandt HC, Grozdanovic Z, Listing J, Kupper H, Braun J, Sieper J. Adalimumab reduces spinal symptoms in active ankylosing spondylitis: clinical and magnetic resonance imaging results of a fifty-two-week open-label trial. Arthritis Rheum. 2006 Feb;54(2):678-81. doi: 10.1002/art.21563. No abstract available.
• Background Hennigan S, Ackermann C, Kavanaugh A. Adalimumab in ankylosing spondylitis: an evidence-based review of its place in therapy. Core Evid. 2008 Jul 31;2(4):295-305.
• Background Kavanaugh A, Klareskog L, van der Heijde D, Li J, Freundlich B, Hooper M. Improvements in clinical response between 12 and 24 weeks in patients with rheumatoid arthritis on etanercept therapy with or without methotrexate. Ann Rheum Dis. 2008 Oct;67(10):1444-7. doi: 10.1136/ard.2008.094524. Epub 2008 Jun 5.
• Background Lyngberg KK, Harreby M, Bentzen H, Frost B, Danneskiold-Samsoe B. Elderly rheumatoid arthritis patients on steroid treatment tolerate physical training without an increase in disease activity. Arch Phys Med Rehabil. 1994 Nov;75(11):1189-95. doi: 10.1016/0003-9993(94)90003-5.
• Background Machado P, Landewe R, Lie E, Kvien TK, Braun J, Baker D, van der Heijde D; Assessment of SpondyloArthritis international Society. Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut-off values for disease activity states and improvement scores. Ann Rheum Dis. 2011 Jan;70(1):47-53. doi: 10.1136/ard.2010.138594. Epub 2010 Nov 10.
• Background Madland TM, Larsen A, Brun JG. S100 proteins calprotectin and S100A12 are related to radiographic changes rather than disease activity in psoriatic arthritis with low disease activity. J Rheumatol. 2007 Oct;34(10):2089-92. Epub 2007 Sep 1.
• Background McIntosh E. The cost of rheumatoid arthritis. Br J Rheumatol. 1996 Aug;35(8):781-90. doi: 10.1093/rheumatology/35.8.781.
• Background Maksymowych WP. Biomarkers in axial spondyloarthritis. Curr Opin Rheumatol. 2015 Jul;27(4):343-8. doi: 10.1097/BOR.0000000000000180.
• Background Maksymowych WP, Dougados M, van der Heijde D, Sieper J, Braun J, Citera G, Van den Bosch F, Logeart I, Wajdula J, Jones H, Marshall L, Bonin R, Pedersen R, Vlahos B, Kotak S, Bukowski JF. Clinical and MRI responses to etanercept in early non-radiographic axial spondyloarthritis: 48-week results from the EMBARK study. Ann Rheum Dis. 2016 Jul;75(7):1328-35. doi: 10.1136/annrheumdis-2015-207596. Epub 2015 Aug 12.
• Background Mounach A, El Maghraoui A. Efficacy and safety of adalimumab in ankylosing spondylitis. Open Access Rheumatol. 2014 Aug 13;6:83-90. doi: 10.2147/OARRR.S44550. eCollection 2014.
• Background Pham T, van der Heijde D, Calin A, Khan MA, van der Linden S, Bellamy N, Dougados M; ASAS Working Group. Initiation of biological agents in patients with ankylosing spondylitis: results of a Delphi study by the ASAS Group. Ann Rheum Dis. 2003 Sep;62(9):812-6. doi: 10.1136/ard.62.9.812.
• Background Trocme C, Gaudin P, Berthier S, Barro C, Zaoui P, Morel F. Human B lymphocytes synthesize the 92-kDa gelatinase, matrix metalloproteinase-9. J Biol Chem. 1998 Aug 7;273(32):20677-84. doi: 10.1074/jbc.273.32.20677.
• Background Trocme C, Marotte H, Baillet A, Pallot-Prades B, Garin J, Grange L, Miossec P, Tebib J, Berger F, Nissen MJ, Juvin R, Morel F, Gaudin P. Apolipoprotein A-I and platelet factor 4 are biomarkers for infliximab response in rheumatoid arthritis. Ann Rheum Dis. 2009 Aug;68(8):1328-33. doi: 10.1136/ard.2008.093153. Epub 2008 Jul 29.
• Background Van Den Bosch F, Kruithof E, Baeten D, Herssens A, de Keyser F, Mielants H, Veys EM. Randomized double-blind comparison of chimeric monoclonal antibody to tumor necrosis factor alpha (infliximab) versus placebo in active spondylarthropathy. Arthritis Rheum. 2002 Mar;46(3):755-65. doi: 10.1002/art.511.
• Background Wendling D, Claudepierre P, Lohse A, Toussirot E, Breban M. [Therapeutic use of anti-TNF-alpha agents in spondyloarthropathies]. Presse Med. 2003 Oct 4;32(32):1517-24. French.
• Background Yelin E, Wanke LA. An assessment of the annual and long-term direct costs of rheumatoid arthritis: the impact of poor function and functional decline. Arthritis Rheum. 1999 Jun;42(6):1209-18. doi: 10.1002/1529-0131(199906)42:63.0.CO;2-M.
• Results Baillet A, Nguyen MVC, Courtier A, Guigue L, Bossert M, Gaudin P, Marotte H, Tournadre A, Wendling D, Mulleman D. Serum biomarkers fail to predict response to adalimumab in axial spondyloarthritis: Results from discovery and validation cohorts. Joint Bone Spine. 2026 Jul;93(4):106055. doi: 10.1016/j.jbspin.2026.106055. Epub 2026 Mar 19. No abstract available.

Drugs

Indications