The advent of IL-17A blockade in ankylosing spondylitis: secukinumab, ixekizumab and beyond

被引:73
作者
Dubash, Sayam [1 ,2 ]
Bridgewood, Charlie [2 ]
McGonagle, Dennis [1 ,2 ]
Marzo-Ortega, Helena [1 ,2 ]
机构
[1] Leeds Teaching Hosp NHS Trust, NIHR Leeds Biomed Res Ctr, Leeds, W Yorkshire, England
[2] Univ Leeds, Leeds Inst Rheumat & Musculoskeletal Med, Leeds, W Yorkshire, England
关键词
Interleukin-17; inhibitors; IL-17; inhibition; IL-17A blockers; ankylosing spondylitis; axial spondyloarthritis; axSpA; secukinumab; ixekizumab; brodalumab; ANTI-INTERLEUKIN-17A MONOCLONAL-ANTIBODY; INNATE LYMPHOID-CELLS; DELTA T-CELLS; DOUBLE-BLIND; RADIOGRAPHIC PROGRESSION; PSORIATIC-ARTHRITIS; BONE-FORMATION; INTERLEUKIN-23; THERAPY; HLA-B27;
D O I
10.1080/1744666X.2019.1561281
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Introduction: Secukinumab, an interleukin-17A (IL-17A) antagonist, is the first non-TNF alpha inhibitor agent licensed for ankylosing spondylitis (AS), which opens up a new era of alternative cytokine targets beyond TNF. Areas covered: This review explores the pathophysiology and scientific evidence behind the use of this new mode of action and discusses the basis for its efficacy and clinical utility in the management of AS. In particular, how the emergent data points towards the efficacy of secukinumab and ixekizumab, a second emergent IL-17A blocker, in AS has helped focus research into the IL-23/17 axis in entheseal driven disease in man and how IL-17A inhibition may be linked to the presence of innate and adaptive immune cell populations capable of IL-17A elaboration in these target tissues. Expert commentary: Collectively these emergent data point towards an efficacious role of IL-17A inhibition strategies targeting AS pathogenesis in a fundamental way whilst carrying a good safety profile.
引用
收藏
页码:123 / 134
页数:12
相关论文
共 93 条
[1]
Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17 [J].
Aggarwal, S ;
Ghilardi, N ;
Xie, MH ;
de Sauvage, FJ ;
Gurney, AL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) :1910-1914
[2]
Altered cytokine expression by macrophages from HLA-B27-positive spondyloarthritis patients without evidence of endoplasmic reticulum stress [J].
Ambarus, Carmen A. ;
Yeremenko, Nataliya ;
Baeten, Dominique L. .
RHEUMATOLOGY ADVANCES IN PRACTICE, 2018, 2 (01) :1-6
[3]
In Situ Analysis of Interleukin-23-and Interleukin-12-Positive Cells in the Spine of Patients With Ankylosing Spondylitis [J].
Appel, Heiner ;
Maier, Rene ;
Bleil, Janine ;
Hempfing, Axel ;
Loddenkemper, Christoph ;
Schlichting, Uwe ;
Syrbe, Uta ;
Sieper, Joachim .
ARTHRITIS AND RHEUMATISM, 2013, 65 (06) :1522-1529
[4]
Baeten D, 2018, ANN RHEUM DIS, P1
[5]
Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis [J].
Baeten, Dominique ;
Sieper, Joachim ;
Braun, Juergen ;
Baraliakos, Xenofon ;
Dougados, Maxime ;
Emery, Paul ;
Deodhar, Atul ;
Porter, Brian ;
Martin, Ruvie ;
Andersson, Mats ;
Mpofu, Shephard ;
Richards, Hanno B. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (26) :2534-2548
[6]
Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial [J].
Baeten, Dominique ;
Baraliakos, Xenofon ;
Braun, Juergen ;
Sieper, Joachim ;
Emery, Paul ;
van der Heijde, Desiree ;
McInnes, Iain ;
van Laar, Jacob M. ;
Landewe, Robert ;
Wordsworth, Paul ;
Wollenhaupt, Juergen ;
Kellner, Herbert ;
Paramarta, Jacqueline ;
Wei, Jiawei ;
Brachat, Arndt ;
Bek, Stephan ;
Laurent, Didier ;
Li, Yali ;
Wang, Ying A. ;
Bertolino, Arthur P. ;
Gsteiger, Sandro ;
Wright, Andrew M. ;
Hueber, Wolfgang .
LANCET, 2013, 382 (9906) :1705-1713
[7]
Which spinal lesions are associated with new bone formation in patients with ankylosing spondylitis treated with anti-TNF agents? A long-term observational study using MRI and conventional radiography [J].
Baraliakos, X. ;
Heldmann, F. ;
Callhoff, J. ;
Listing, J. ;
Appelboom, T. ;
Brandt, J. ;
Van den Bosch, F. ;
Breban, M. ;
Burmester, G. R. ;
Dougados, M. ;
Emery, P. ;
Gaston, H. ;
Grunke, M. ;
Van Der Horst-Bruinsma, I. E. ;
Landewe, R. ;
Leirisalo-Repo, M. ;
Sieper, J. ;
De Vlam, K. ;
Pappas, D. ;
Kiltz, U. ;
Van Der Heijde, D. ;
Braun, J. .
ANNALS OF THE RHEUMATIC DISEASES, 2014, 73 (10) :1819-1825
[8]
Learning from the youngsters: ixekizumab in active ankylosing spondylitis [J].
Baraliakos, Xenofon ;
Braun, Juergen .
LANCET, 2018, 392 (10163) :2415-2416
[9]
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 [J].
Baraliakos, Xenofon ;
Haibel, Hildrun ;
Listing, Joachim ;
Sieper, Joachim ;
Braun, Juergen .
ANNALS OF THE RHEUMATIC DISEASES, 2014, 73 (04) :710-715
[10]
The anatomical basis for disease localisation in seronegative spondyloarthropathy at entheses and related sites [J].
Benjamin, M ;
McGonagle, D .
JOURNAL OF ANATOMY, 2001, 199 :503-526