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Review

IL-17 inhibition in axial spondyloarthritis: current and future perspectives

ORCID Icon &
Pages 631-641 | Received 11 Feb 2019, Accepted 05 Apr 2019, Published online: 19 Apr 2019

References

  • Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet. 2017;390(10089):73–84.
  • 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(6):777–783.
  • Ranganathan V, Gracey E, Brown MA, et al. Pathogenesis of ankylosing spondylitis - recent advances and future directions. Nat Rev Rheumatol. 2017;13(6):359–367.
  • Stolwijk C, Boonen A, van Tubergen A, et al. Epidemiology of spondyloarthritis. Rheum Dis Clin North Am. 2012;38(3):441–476.
  • Bowness P. HLA-B27. Annu Rev Immunol. 2015;33:29–48.
  • Simone D, Al Mossawi MH, Bowness P. Progress in our understanding of the pathogenesis of ankylosing spondylitis. Rheumatology. 2018;57(suppl_6):vi4–vi9.
  • Pedersen SJ, Maksymowych WP. Beyond the TNF-α inhibitors: new and emerging targeted therapies for patients with axial spondyloarthritis and their relation to pathophysiology. Drugs. 2018;78(14):1397–1418.
  • De Vos M, Mielants H, Cuvelier C, et al. Long-term evolution of gut inflammation in patients with spondyloarthropathy. Gastroenterology. 1996;110(6):1696–1703.
  • Gill T, Asquith M, Rosenbaum JT, et al. The intestinal microbiome in spondyloarthritis. Curr Opin Rheumatol. 2015;27(4):319–325.
  • Cortes A, Hadler J, Pointon JP, et al. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet. 2013;45(7):730–738.
  • Han Q, Das S, Hirano M, et al. Characterization of lamprey IL-17 family members and their receptors. J Immunol. 2015;195(11):5440–5451.
  • Miossec P, Kolls JK. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012;11(10):763–776.
  • Veldhoen M. Interleukin 17 is a chief orchestrator of immunity. Nat Immunol. 2017;18(6):612–621.
  • Rouvier E, Luciani MF, Mattei MG, et al. CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol. 1993;150(12):5445–5456.
  • Yao Z, Painter SL, Fanslow WC, et al. Human IL-17: a novel cytokine derived from T cells. J Immunol. 1995;155(12):5483–5486.
  • Moseley TA, Haudenschild DR, Rose L, et al. Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev. 2003;14(2):155–174.
  • Chang SH, Dong C. A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses. Cell Res. 2007;17(5):435–440.
  • Taams LS, Steel KJA, Srenathan U, et al. IL-17 in the immunopathogenesis of spondyloarthritis. Nat Rev Rheumatol. 2018;14(8):453–466.
  • Jandus C, Bioley G, Rivals JP, et al. Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum. 2008;58(8):2307–2317.
  • Al-Mossawi MH, Chen L, Fang H, et al. Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis. Nat Commun. 2017;8(1):1510.
  • Liang Y, Pan HF, Ye DQ. Tc17 cells in immunity and systemic autoimmunity. Int Rev Immunol. 2015;34(4):318–331.
  • Steel K, Wu S-Y, Srenathan U, et al. O016 Synovial IL-17+ CD8+ T cells are a pro-inflammatory tissue resident population enriched in spondyloarthritis. Ann Rheum Dis. 2018;77(Suppl 1):A8–A9.
  • Kenna TJ, Davidson SI, Duan R, et al. Enrichment of circulating interleukin-17-secreting interleukin-23 receptor-positive gamma/delta T cells in patients with active ankylosing spondylitis. Arthritis Rheum. 2012;64(5):1420–1429.
  • Gracey E, Qaiyum Z, Almaghlouth I, et al. IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, which contribute to the Th17-axis in ankylosing spondylitis. Ann Rheum Dis. 2016;75(12):2124–2132.
  • Hayashi E, Chiba A, Tada K, et al. Involvement of mucosal-associated invariant T cells in ankylosing spondylitis. J Rheumatol. 2016;43(9):1695–1703.
  • Yoshiga Y, Goto D, Segawa S, et al. Invariant NKT cells produce IL-17 through IL-23-dependent and -independent pathways with potential modulation of Th17 response in collagen-induced arthritis. Int J Mol Med. 2008;22(3):369–374.
  • Noordenbos T, Yeremenko N, Gofita I, et al. Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis. Arthritis Rheumatism. 2012;64(1):99–109.
  • Ciccia F, Guggino G, Rizzo A, et al. Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis. Ann Rheum Dis. 2015;74(9):1739–1747.
  • Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol. 2009;9(8):556–567.
  • Toy D, Kugler D, Wolfson M, et al. Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol. 2006;177(1):36–39.
  • Kuestner RE, Taft DW, Haran A, et al. Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F. J Immunol. 2007;179(8):5462–5473.
  • Gu C, Wu L, Li X. IL-17 family: cytokines, receptors and signaling. Cytokine. 2013;64(2):477–485.
  • Lubberts E. The IL-23–IL-17 axis in inflammatory arthritis. Nat Rev Rheumatol. 2015;11(7):415–429.
  • Lee JS, Tato CM, Joyce-Shaikh B, et al. Interleukin-23-independent IL-17 production regulates intestinal epithelial permeability. Immunity. 2015;43(4):727–738.
  • Li Z, Brown MA. Progress of genome-wide association studies of ankylosing spondylitis. Clin Transl Immunology. 2017;6(12):e163.
  • Vieira-Sousa E, van Duivenvoorde LM, Fonseca JE, et al. Review: animal models as a tool to dissect pivotal pathways driving spondyloarthritis. Arthritis Rheumatol. 2015;67(11):2813–2827.
  • Lubberts E, Koenders MI, van den Berg WB. The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal models. Arthritis Res Ther. 2005;7(1):29–37.
  • Wendling D. The gut in spondyloarthritis. Joint Bone Spine. 2016;83(4):401–405.
  • Appel H, Maier R, Wu P, et al. Analysis of IL-17(+) cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response. Arthritis Res Ther. 2011;13(3):R95.
  • Jansen DT, Hameetman M, van Bergen J, et al. IL-17-producing CD4+ T cells are increased in early, active axial spondyloarthritis including patients without imaging abnormalities. Rheumatology (Oxford). 2015;54(4):728–735.
  • Wendling D, Cedoz JP, Racadot E, et al. Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis. Joint Bone Spine. 2007;74(3):304–305.
  • Taylan A, Sari I, Kozaci DL, et al. Evaluation of the T helper 17 axis in ankylosing spondylitis. Rheumatol Int. 2012;32(8):2511–2515.
  • Chen WS, Chang YS, Lin KC, et al. Association of serum interleukin-17 and interleukin-23 levels with disease activity in Chinese patients with ankylosing spondylitis. J Chin Med Assoc. 2012;75(7):303–308.
  • Xueyi L, Lina C, Zhenbiao W, et al. Levels of circulating Th17 cells and regulatory T cells in ankylosing spondylitis patients with an inadequate response to anti-TNF-alpha therapy. J Clin Immunol. 2013;33(1):151–161.
  • 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(6):978–991.
  • Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis — results of two phase 3 trials. N Engl J Med. 2014;371(4):326–338.
  • Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373(14):1329–1339.
  • Baeten D, Baraliakos X, Braun J, et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2013;382(9906):1705–1713.
  • Baraliakos X, Borah B, Braun J, et al. Long-term effects of secukinumab on MRI findings in relation to clinical efficacy in subjects with active ankylosing spondylitis: an observational study. Ann Rheum Dis. 2016;75(2):408–412.
  • 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.
  • 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(1):285.
  • Kivitz AJ, Wagner U, Dokoupilova E, et al. Efficacy and safety of secukinumab 150 mg with and without loading regimen in ankylosing spondylitis: 104-week results from MEASURE 4 study. Rheumatol Ther. 2018;5(2):447–462.
  • Deodhar AA, Dougados M, Baeten DL, et al. Effect of secukinumab on patient-reported outcomes in patients with active ankylosing spondylitis: A phase III randomized trial (MEASURE 1). Arthritis Rheumatol. 2016;68(12):2901–2910.
  • Braun J, Baraliakos X, Deodhar A, et al. Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study. Ann Rheum Dis. 2017;76(6):1070–1077.
  • Baraliakos X, Kivitz AJ, Deodhar AA, et al. Long-term effects of interleukin-17A inhibition with secukinumab in active ankylosing spondylitis: 3-year efficacy and safety results from an extension of the phase 3 MEASURE 1 trial. Clin Exp Rheumatol. 2018;36(1):50–55.
  • 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. DOI:10.1093/rheumatology/key375.
  • X BJ B, Deodhar AA, Poddubnyy D, et al. Long-term evaluation of secukinumab in ankylosing spondylitis: 5 year efficacy and safety results from a phase 3 trial [abstract]. Arthritis Rheumatol. 2018;70(suppl 10). [cited 2018 Dec 18]. Available from: https://acrabstractsorg/abstract/long-term-evaluation-of-secukinumab-in-ankylosing-spondylitis-5-year-efficacy-and-safety-results-from-a-phase-3-trial/
  • 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(3):571–592.
  • Marzo-Ortega H, Sieper J, Kivitz A, et al. Secukinumab and sustained improvement in signs and symptoms of patients with active ankylosing spondylitis through two years: results From a phase III study. Arthritis Care Res (Hoboken). 2017;69(7):1020–1029.
  • Deodhar A, Conaghan PG, Kvien TK, et al. Secukinumab provides rapid and persistent relief in pain and fatigue symptoms in patients with ankylosing spondylitis irrespective of baseline C-reactive protein levels or prior tumour necrosis factor inhibitor therapy: 2-year data from the MEASURE 2 study. Clin Exp Rheumatol. 2019;37(2):260–269.
  • Marzo-Ortega H, Sieper J, Kivitz A, et al. Secukinumab provides sustained improvements in the signs and symptoms of active ankylosing spondylitis with high retention rate: 3-year results from the phase III trial, MEASURE 2. RMD Open. 2017;3(2):e000592.
  • Marzo-Ortega H, Sieper J, Kivitz A, et al. SAT0283 Secukinumab 150 mg provides sustained improvements in the signs and symptoms of active ankylosing spondylitis with high retention rate: 4-year results from the phase iii trial, measure 2. Ann Rheum Dis. 2018;77(Suppl 2):1005.
  • 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(2):e000749.
  • Emery P, Van Keep M, Beard S, et al. Cost effectiveness of secukinumab for the treatment of active ankylosing spondylitis in the UK. PharmacoEconomics. 2018;36(8):1015–1027.
  • Colombo GL, Di Matteo S, Martinotti C, et al. Budget impact model of secukinumab for the treatment of moderate-to-severe psoriasis, psoriatic arthritis, and ankylosing spondylitis in Italy: a cross-indication initiative. Clinicon Econ Outcomes Res. 2018;10:477–491.
  • Purmonen T, Tormalehto S, Wahlman H, et al. Budget impact analysis of secukinumab versus adalimumab in the treatment of ankylosing spondylitis. J Med Econ. 2019;22(2):151–157.
  • Goeree R, Chiva-Razavi S, Gunda P, et al. Cost-effectiveness analysis of secukinumab in ankylosing spondylitis from the Canadian perspective. J Med Econ. 2019;22(1):45–52.
  • van der Heijde D, Braun J, Deodhar A, et al. Modified stoke ankylosing spondylitis spinal score as an outcome measure to assess the impact of treatment on structural progression in ankylosing spondylitis. Rheumatology (Oxford). 2018;58(3):388–400.
  • Poddubnyy D, Sieper J. Mechanism of new bone formation in axial spondyloarthritis. Curr Rheumatol Rep. 2017;19(9):55.
  • Braun J, Haibel H, de Hooge M, et al. SAT0259 Low rate of spinal radiographic progression over 2 years in ankylosing spondylitis patients treated with secukinumab: a historical cohort comparison. Ann Rheum Dis. 2018;77(Suppl 2):992–993.
  • Liu L, Lu J, Allan BW, et al. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A. J Inflamm Res. 2016;9:39–50.
  • 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(10163):2441–2451.
  • 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. 2019;71(4):599–611.
  • Glatt S, Helmer E, Haier B, et al. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017;83(5):991–1001.
  • van der Heijde D, Gensler LS, Deodhar A, et al. LB0001 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.
  • Papp KA, Reid C, Foley P, et al. Anti-IL-17 receptor antibody AMG 827 leads to rapid clinical response in subjects with moderate to severe psoriasis: results from a phase I, randomized, placebo-controlled trial. J Invest Dermatol. 2012;132(10):2466–2469.
  • Lebwohl M, Strober B, Menter A, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015;373(14):1318–1328.
  • Mease PJ, Genovese MC, Greenwald MW, et al. Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis. N Engl J Med. 2014;370(24):2295–2306.
  • Lebwohl MG, Papp KA, Marangell LB, et al. Psychiatric adverse events during treatment with brodalumab: analysis of psoriasis clinical trials. J Am Acad Dermatol. 2018;78(1):81–89.e5.
  • Mazurov V, Erdes S, Kunder E, et al. OP0028 Efficacy and safety of bcd-085, a novel il-17 inhibitor, in ankylosing spondylitis. results of phase 2 clinical study. Ann Rheum Dis. 2018;77(Suppl2):64.

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