A new target in the treatment of psoriatic arthritis. Why interleukin-17?
Authors:
L. Šedová
Authors‘ workplace:
Revmatologický ústav, Praha
Published in:
Čes. Revmatol., 27, 2019, No. 2, p. 78-85.
Category:
Review Article
Overview
Interleukin 17 is a pro-inflammatory cytokine that plays an important role in the development of psoriasis, psoriatic arthritis and other autoimmune diseases. It is produced by various cells, especially Th17 lymphocytes. Its inhibition has a pronounced anti-inflammatory effect, manifested, for example, by the suppression of psoriasis skin manifestations and by the reduction of psoriatic arthritis activity. The pathway to achieve inhibition of IL-17 is the use of monoclonal antibodies against IL-17 as well as its receptors, through antibodies against the p40 subunit shared by IL-12 and 23, and preventing their interaction with the receptor, subsequent signalling, differentiation, and cytokine production, including IL-17. IL-17 inhibitors are a new, very effective generation of psoriasis biological therapy, as well as a significant extension of the biological spondyloarthritis therapies to the first drugs with a new, different mechanism of action. Therefore, IL-17 inhibitors represent similar advances as TNF-α inhibitors in rheumatoid arthritis years ago.
Keywords:
Psoriasis – biological therapy – anti-TNF-α – anti-IL-12/23 – IL-17 – anti-IL-17 – Psoriatic arthritis
Sources
1. Kim BS, Park YJ, Chung Y. Targeting IL-17 in autoimmunity and inflammation. Arch Pharm Res 2016; 39: 1537–1547.
2. Gao SF, Zhong B, Lin D. Regulation of T helper cell differentiation by E3 ubiquitin ligases and deubiquitinating enzymes. Int Immunopharmacol. 2017; 42: 150–156.
3. Gizinski AM, Fox DA. T cell subsets and their role in the pathogenesis of rheumatic disease. Curr Opin Rheumatol 2014; 26: 204–210.
4. Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol 2009; 9: 556–567.
5. Smith JA. The Bench-to-Bedside Story of IL-17 and the therapeutic efficacy of its targeting in spondyloarthritis. Curr Rheumatol Rep 2016; 18: 33.
6. Chang SH, Dong C. A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses. Cell Res 2007; 17: 435–440.
7. Wright JF, Guo Y, Quazi A, et al. Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells. J Biol Chem 2007; 282: 13447–13455.
8. Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 2008; 28: 454–467.
9. Kleinschek MA, Owyang AM, Joyce-Shaikh B, et al. IL-25 regulates Th17 function in autoimmune inflammation. J Exp Med 2007; 204: 161–170.
10. Miossec P. Update on interleukin-17: a role in the pathogenesis of inflammatory arthritis and implication for clinical practice RMD Open 2017; 3: e000284.
11. McGeachy MJ, Chen Y, Tato CM, et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol 2009; 10: 314–324.
12. Adamopoulos IE, Chao CC, Geissler R, et al. Interleukin-17A upregulates receptor activator of NF-kappa B on osteoclast precursors. Arthritis Res Ther 2010; 12: R29.
13. Chen L, Wei XQ, Evans B, et al. IL-23 promotes osteoclast formation by up-regulation of receptor activator of NF-kappa B (RANK) expression in myeloid precursor cells. Eur J Immunol 2008; 38: 2845–2854.
14. Yago T, Nanke Y, Ichikawa N, et al. IL-17 induces osteoclastogenesis from human monocytes alone in the absence of osteoblasts, which is potently inhibited by anti-TNF-alpha antibody: a novel mechanism of osteoclastogenesis by IL-17. J Cell Biochem 2009; 108: 947–955.
15. Kotake S, Udagawa N, Takahashi N, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 1999; 103: 1345–1352.
16. Huang H, Kim HJ, Chang EJ, et al. IL-17 stimulates the proliferation and differentiation of human mesenchymal stem cells: implications for bone remodelling. Cell Death Differ 2009; 16: 1332–1343.
17. Bartlett HS, Million RP. Targeting the IL-17-T(H)17 pathway. Nat Rev Drug Discov 2015; 14: 11–12.
18. Ogdie A, Weiss P. The epidemiology of psoriatic arthritis. Rheum Dis Clin North Am 2015; 41: 545–568.
19. Michalek IM, Loring B, John SM. A systematic review of worldwide epidemiology of psoriasis. Eur Acad Dermatol Venereol 2017; 31: 205–212.
20. Benham H, Norris P, Goodall J, et al. Th17 and Th22 cells in psoriatic arthritis and psoriasis. Arthritis Res Ther 2013; 15: R136.
21. Mashiko S, Bouguermouh S, Rubio M, et al. Human mast cells are major IL-22 producers in patients with psoriasis and atopic dermatitis. J Allergy Clin Immunol 2015; 136: 351–359.
22. Balato A, Scala E, Balato N, et al. Biologics that inhibit the Th17 pathway and related cytokines to treat inflammatory disorders. Expert Opin Biol Ther 2017; 17: 1363–1374.
23. Menon B, Gullick NJ, Walter GJ, et al. Interleukin-17+CD8+ T cells are enriched in the joints of patients with psoriatic arthritis and correlate with disease activity and joint damage progression. Arthritis Rheum 2014; 66: 1272–1281.
24. Celis R, Planell N, Fernandez-Sueiro JL, et al. Synovial cytokine expression in psoriatic arthritis and associations with lymphoid neogenesis and clinical features. Arthritis Res Ther 2012; 14: R93.
25. Patel DD, Kuchroo VK. Th17 cell pathway in human immunity: lessons from genetics and therapeutic interventions. Immunity 2015; 43: 1040–1051.
26. Mease P. Inhibition of interleukin-17, interleukin-23 and the TH17 cell pathway in the treatment of psoriatic arthritis and psoriasis. Curr Opin Rheumatol 2015; 27: 127–133.
27. Koenders MI, van den Berg WB. Secukinumab for rheumatology: development and its potential place in therapy. Drug Des Devel Ther 2016; 10: 2069–2080.
28. Papp KA, Langley RG, Sigurgeirsson B, et al. Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study. Br J Dermatol 2013; 168: 412–421.
29. Rich P, Sigurgeirsson B, Thaci D, et al. Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled, phase II regimen-finding study. Br J Dermatol 2013; 168: 402–411.
30. Langley RG, Elewski BE, Lebwohl M, et al. ERASURE Study Group. FIXTURE Study Group. Secukinumab in plaque psoriasis – results of two phase 3 trials. N Engl J Med 2014; 371: 326–338.
31. Langley RG, Ellis CN. Evaluating psoriasis with psoriasis area and severity index, psoriasis global assessment, and lattice system physician’s global assessment. J Am Acad Dermatol 2004; 51: 563–569.
32. Thaçi D, Blauvelt A, Reich K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol 2015; 73: 400–409.
33. Mease P, McInnes IB. Secukinumab: a new treatment option for psoriatic arthritis. Rheumatol Ther 2016; 3: 5–29.
34. Cingoz O, Langley RG, Elewski BE, et al. Ustekinumab. Mabs 2009; 1: 216–221.
35. Kavanaugh A, Mease PJ, Reimold AM, et al. Secukinumab for long-term treatment of psoriatic arthritis: a two-year follow up from a phase III, randomized, double-blind placebo-controlled study. Arthritis Care Res (Hoboken) 2017; 69: 347–355.
36. 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.
37. Toussirot E. Ixekizumab: an anti-IL17A monoclonal antibody for the treatment of psoriatic arthritis. Expert Opin Biol Ther 2018; 1: 101–107.
38. Leonardi C, Matheson R, Zachariae C, et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med 2012; 366(13): 1190–1199.
39. Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. N Engl J Med 2016; 375: 345–356.
40. Griffiths CEM, Reich K, Lebwohl M, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet 2015; 386(9993): 541–551.
41. Gordon KB, Leonardi CL, Lebwohl M, et al. A 52-week, open-label study of the efficacy and safety of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with chronic plaque psoriasis. J Am Acad Dermatol 2014; 71: 1176–1182.
42. Mease PJ, van der Heijde D, Ritchlin CT, et al. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo – controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis 2017; 76: 79–87.
43. Nash P, Kirkham B, Okada M, et al. SPIRIT-P2 Study Group. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet 2017; 389(10086): 2317–2327.
44. Leonardi C, Matheson R, Zachariae C, et al. Anti-interleukin-17monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med 2012; 366(13): 1190–1199.
45. Bauer E, Lucier J, Furst DE. Brodalumab – an IL-17RA monoclonal antibody for psoriasis and psoriatic arthritis. Expert Opin Biol Ther 2015; 15: 883–893.
46. Papp KA, Reich K, Paul C, et al. A prospective phase 3, randomised, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol 2016; 175(2): 273–286.
47. Lebwohl M, Strober B, Menter A, et al. Phase 3 studies comparing brodalumab with Ustekinumab in psoriasis. N Engl J Med 2015; 373: 1318–1328.
48. Ghoreschi K, Laurence A, Yang XP, et al. Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling. Nature 2010; 467: 967–971.
49. Oppmann B, Lesley R, Blom B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar aswell as distinct from IL-12. Immunity 2000; 13(5): 715–725.
50. Lyakh L, Trinchieri G, Provezza L, et al. Regulation of interleukin-12/interleukin-23 production and the T-helper 17 response in humans. Immunol Rev 2008; 226: 112–131.
51. Devos SA, Van Den Bossche N, De Vos M, et al. Adverse skin reactions to anti-TNF-alpha monoclonal antibody therapy. Dermatology 2003; 206: 388–390.
52. Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev 2010; 10: 479–489.
53. Khader SA, Gopal R. IL-17 in protective immunity to intracellular pathogens. Virulence 2010; 1: 423–427.
54. Murphy CA, Langrish CL, Chen Y, et al. Divergent pro- and anti-inflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 2003; 198: 1951–1957.
55. van de Kerkhof PC. Novel biologic therapies in development targeting IL-12/IL-23. J Eur Acad Dermatol Venereol 2010; 24(Suppl 6): 5–9.
56. Yeilding N, Szapary P, Brodmerkel C, et al. Development of the IL-12/23 antagonist ustekinumab in psoriasis: past, present, and future perspectives. Ann NY Sci 2011; 1222: 30–39.
57. Scherl EJ, Kumar S, Warren RU. Review of the safety and efficacy of ustekinumab. Ther Adv Gastroenterol 2010; 3: 321–328.
58. Kaushik SB, Lebwohl MG. Psoriasis: Which therapy for which patient: Psoriasis comorbidities and preferred systemic agents. J Am Acad Dermatol 2019; 80: 27–40.
59. Baker KF, Isaacs JD. Novel therapies for immune-mediated inflammatory diseases: what can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis? Ann Rheum Dis 2018; 77: 175–187.
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