Ингибиторы ИЛ23/ИЛ17 при иммуновоспалительных ревматических заболеваниях: новые горизонты
https://doi.org/10.14412/1995-4484-2019-400-406
Аннотация
В последние годы большое внимание привлекают Th17-клетки, патологическая активация которых играет ведущую роль в развитии широкого спектра иммуновоспалительных заболеваний (ИВЗ) человека, включая ревматоидный артрит, псориаз, анкилозирующий спондилит, псориатический артрит, воспалительные заболевания кишечника и др. Это послужило стимулом для разработки новых генно-инженерных биологических препаратов и «малых» молекул, механизм действия которых основан на блокировании патологических эффектов интерлейкина 17 (ИЛ17), других связанных с активацией Th17-клеток цитокинов или сигнальных путей, регулирующих эффекты этих цитокинов. В обзоре обсуждаются современные представления о механизмах регуляции образования и функциональной активности цитокинов семейства ИЛ17, а также доказательства значения этих цитокинов в патогенезе ИВЗ.
Об авторах
Е. Л. НасоновРоссия
115522, Москва, Каширское шоссе, 34А
119991, Москва, ул. Трубецкая, 8, стр. 2
Т. В. Коротаева
Россия
115522, Москва, Каширское шоссе, 34А
Т. В. Дубинина
Россия
115522, Москва, Каширское шоссе, 34А
А. М. Лила
Россия
115522, Москва, Каширское шоссе, 34А
125993, Москва, ул. Баррикадная, 2/1, стр. 1
Список литературы
1. El-Gabalawy H, Guenther LC, Bernstein CN. Epidemiology of immune-mediated inflammatory diseases: incidence, prevalence, natural history, and comorbidities. J Rheumatol Suppl. 2010;85:2-10. doi: 10.3899/jrheum.091461
2. Насонов ЕЛ, Александрова ЕН, Новиков АА. Аутоиммунные ревматические заболевания – проблемы иммунопатологии и персонифицированной терапии. Вестник Российской академии медицинских наук. 2015;70(2):169-82
3. Wang L, Wang FS, Gershwin ME. Human autoimmune diseases: a comprehensive update. J Intern Med. 2015;278:369-95. doi: 10.1111/joim.12395
4. Parkes M, Cortes A, van Heel DA, Brown MA. Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat Rev Genet. 2013;14:661-73. doi: 10.1038/nrg3502
5. Ellinghaus D, Jostins L, Spain SL, et al. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. Nat Genet. 2016;48:510-8. doi: 10.1038/ng.3528
6. Cotsapas C, Voight BF, Rossin E, et al. Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet. 2011;7:e1002254. doi: 10.1371/journal.pgen.1002254
7. Farh KK, Marson A, Zhu J, et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature. 2015;518:337-43. doi: 10.1038/nature13835
8. Annuziato F, Romagnani C, Romagnani S. The 3 major types of innate and adaptive cell-mediated effector immunity. J Allergy Clin Immunol. 2015;135:626-35. doi: 10.1016/j.jaci.2014.11.001
9. Isalovic N, Daigo K, Mantovani A, Selmi C. Interleukin-17 and innate immunity in infections and chronic inflammation. J Autoimmun. 2015;60:1-11. doi: 10.1016/j.jaut.2015.04.006
10. Miossec P, Kolls JK. Targeting IL-17 and Th17 cells in chronic inflammation. Nat Rev Drug Discov. 2012;11:763-76. doi: 10.1038/nrd3794
11. Beringer A, Miossec P. Systemic effects of IL-17 in inflammatory arthritis. Nat Rev Rheumatol. 2019 Jun 21. doi: 10.1038/s41584-019-0243-5
12. Beringer A, Noack M, Miossec P. IL-17 in chronic inflammation: from discovery to targeting. Trends Molec Med. 2016;22:230-41. doi: 10.1016/j.molmed.2016.01.001
13. Benedetti G, Miossec P. Interleukin 17 contributes to the chronicity of inflammatory diseases such as rheumatoid arthritis. Eur J Immunol. 2014;44:339-47. doi: 10.1002/eji.201344184
14. Fragoulis GE, Siebert S, McInnes IB. Therapeutic targeting of IL-17 and IL-23 cytokines in immune-mediated disease. Ann Rev Med. 2016:67:337-53. doi: 10.1146/annurev-med-051914-0219444
15. Allam G, Abdel-Moneim A, Gaber AM. The pleiotropic role of interleukin-17 in atherosclerosis. Biomed Pharmacother. 2018;106:1412-8. doi: 10.1016/j.biopha.2018.07.110
16. Robert M, Miossec P. Effects of Interleukin 17 on the cardiovascular system. Autoimmun Rev. 2017;16(9):984-91. doi: 10.1016/j.autrev.2017.07.009
17. Cortvrindt C, Speeckaert R, Moerman A, et al. The role of interleukin-17A in the pathogenesis of kidney diseases. Pathology. 2017;49(3):247-58. doi: 10.1016/j.pathol.2017.01.003
18. Ramani K, Biswas PS. Interleukin-17: Friend or foe in organ fibrosis. Cytokine. 2019;120:282-8. doi: 10.1016/j.cyto.2018.11.003
19. Gurczynski SJ, Moore BB. IL-17 in the lung: the good, the bad, and the ugly. Am J Physiol Lung Cell Mol Physiol. 2018;314(1):L6-L16. doi: 10.1152/ajplung.00344.2
20. Chackelevicius CM, Gambaro SE, Tiribelli C, Rosso N. Th17 involvement in nonalcoholic fatty liver disease progression to nonalcoholic steatohepatitis. World J Gastroenterol. 2016 Nov 7;22(41):9096-103.
21. Gaffen SL. Recent advances in the IL-17 cytokine family. Curr Opin Immunol. 2011;23:613-9. doi: 10.1016/j.coi.2011.07.006
22. Насонов ЕЛ. Новые возможности фармакотерапии иммуновоспалительных ревматических заболеваний: фокус на ингибиторы интерлейкина 17. Научно-практическая ревматология. 2017;55(1):68-86 doi: 10.14412/1995-4484-2017-68-86
23. Tait Wojno ED, Hunter CA, Stumhofer JS. The Immunobiology of the Interleukin-12 Family: Room for Discovery. Immunity. 2019;50(4):851-70. doi: 10.1016/j.immuni.2019.03.011
24. Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev. 2014;13:668-77. doi: 10.1016/j.autrev.2013.12.004
25. Sabat R, Ouyang W, Wolk K. Therapeutic opportunities of the IL-22-IL-22R1 system. Nat Rev Drug Discov. 2014;13:21-38. doi: 10.1038/nrd4176
26. Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol. 2010;10:479-89. doi: 10.1038/nri2800
27. Schwartz DM, Kanno Y, Villarino A, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16(12):843-62. doi: 10.1038/nrd.2017.201
28. Gadina M, Johnson C, Schwartz D, et al. Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs. J Leukoc Biol. 2018;104(3):499-514. doi: 10.1002/JLB.5RI0218-084R
29. Насонов ЕЛ, Лила АМ. Ингибиторы Янус-киназ при иммуновоспалительных ревматических заболеваниях: новые возможности и перспективы. Научно-практическая ревматология. 2019;57(1):8-16 doi: 10.14412/1995-4484-2019-8-16
30. Robert M, Miossec P. IL-17 in Rheumatoid Arthritis and Precision Medicine: From Synovitis Expression to Circulating Bioactive Levels. Front Med (Lausanne). 2019;5:364. doi: 10.3389/fmed.2018.00364
31. Kunwar S, Dahal K, Sharma S. Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review and metaanalysis of randomized controlled trials. Rheumatol Int. 2016;36:1065-75. doi: 10.1007/s00296-016-3480-9
32. Pfeifle R, Rothe T, Ipseiz N, et al. Regulation of autoantibody activity by the IL-23-TH17 axis determines the onset of autoimmune disease. Nat Immunol. 2017;18(1):104-13. doi: 10.1038/ni.3579
33. Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis – results of two phase 3 trials. N Engl J Med. 2014;371:326-38. doi: 10.1056/NEJMoa1314258
34. Griffiths CE, 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;386:541-51. doi: 10.1016/S0140-6736(15)60125-8
35. Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76:405-17. doi: 10.1016/j.jaad.2016.11.041
36. Gordon KB, Blauvelt A, Foley P, et al. Efficacy of guselkumab in subpopulations of patients with moderate-to-severe plaque psoriasis: a pooled analysis of the phase III VOYAGE 1 and VOYAGE 2 studies. Br J Dermatol. 2018;178(1):132-9. doi: 10.1111/bjd.16008
37. Reich K, Papp KA, Blauvelt A, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet. 2017;390:276-88. doi: 10.1016/S0140-6736(17)31279-5
38. Papp KA, Reich K, Blauvelt A, et al. Efficacy of tildrakizumab for moderate-to-severe plaque psoriasis: pooled analysis of three randomized controlled trials at weeks 12 and 28. Eur Acad Dermatol Venereol. 2019;33(6):1098-106. doi: 10.1111/jdv.15400
39. Papp KA, Blauvelt A, Bukhalo M, et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med. 2017;376:1551-60. doi: 10.1056/NEJMoa1607017
40. Gordon KB, Strober B, Lebwohl M, et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018;392(10148):650-61. doi: 10.1016/S0140-6736(18)31713-6
41. Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab inhibition of interleukin-17a in patients with psoriatic arthritis. N Engl J Med. 2015;373:1329-39. doi: 10.1056/NEJMoa1412679
42. McInnes IB, Mease PJ, Kirkham B, et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebocontrolled, phase 3 trial. Lancet. 2015;386:1137-46. doi: 10.1016/S0140-6736(15)61134-5
43. 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. doi: 10.1136/annrheumdis-2016-209709
44. McInnes IB, Kavanaugh A, Gottlieb AB, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet. 2013;382:780-9. doi: 10.1016/S0140-6736(13)60594-2
45. Ritchlin C, Rahman P, Kavanaugh A, et al. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional nonbiological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, doubleblind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis. 2014;73:990-9. doi: 10.1136/annrheumdis-2013-204655
46. Belasco J, Louie JS, Gulati N, et al. Comparative genomic profiling of synovium versus skin lesions in psoriatic arthritis. Arthritis Rheum. 2015;67:934-44. doi: 10.1002/art.38995
47. 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 Rheum. 2019;71(2):258-70. doi: 10.1002/art.40728
48. Mease P. Ustekinumab Fails to Show Efficacy in a Phase III Axial Spondyloarthritis Program: The Importance of Negative Results. Arthritis Rheum. 2019;71(2):179-81. doi: 10.1002/art.40759
49. 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(9):1295-302. doi: 10.1136/annrheumdis-2018-213328
50. Baeten D, Sieper J, Braun J, et al. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med. 2015;373(26):2534-48. doi: 10.1056/NEJMoa1505066
51. 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):1070-7. doi: 10.1136/annrheumdis-2016-209730
52. 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. 2018;58(5):859-68. doi: 10.1093/rheumatology/key3
53. Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2016;375:1946-60. doi: 10.1056/NEJMoa1602773
54. Feagan BG, Sandborn WJ, D'Haens G, et al. Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, doubleblind, placebo-controlled phase 2 study. Lancet. 2017;389:1699-709. doi: 10.1016/S0140-6736(17)30570-6
55. 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 placebocontrolled trial. Gut. 2012;61:1693-700. doi: 10.1136/gutjnl-2011-301668
56. Targan SR, Feagan B, Vermeire S, et al. A randomized, doubleblind, placebo-controlled phase 2 study of brodalumab in patients with moderate-to-severe Crohn's disease. Am J Gastroenterol. 2016;111:1599-607. doi: 10.1038/ajg.2016.298
57. Lee JS, Tato CM, Joyce-Shaikh B, et al. Interleukin-23-independent il-17 production regulates intestinal epithelial permeability. Immunity. 2015;43:727-38. doi: 10.1016/j.immuni.2015.09.003
58. Jacques P, van Praet L, Carron P, et al. Pathophysiology and role of the gastrointestinal system in spondyloarthritides. Rheum Dis Clin North Am. 2012;38:569-82. doi: 10.1016/j.rdc.2012.08.012
59. Hasegawa E, Sonoda KH, Shichita T, et al. IL-23-independent induction of IL-17 from γδT cells and innate lymphoid cells promotes experimental intraocular neovascularization. J Immunol. 2013;190:1778-87. doi: 10.4049/jimmunol.1202495
60. Garbers C, Heink S, Korn T, Rose-John S. Interleukin-6: designing specific therapeutics for a complex cytokine. Nat Rev Drug Discov. 2018 Jun;17(6):395-412. doi: 10.1038/nrd.2018.45
61. Насонов ЕЛ, Лила АМ. Ингибиция интерлейкина 6 при иммуновоспалительных ревматических заболеваниях: достижения, перспективы и надежды. Научно-практическая ревматология. 2017;55(6):590-9 doi: 10.14412/1995-4484-2017-590-599
62. Miyagawa I, Nakayamada S, Nakano K, et al. Precision medicine using different biological DMARDs based on characteristic phenotypes of peripheral T helper cells in psoriatic arthritis. Rheumatology (Oxford). 2019;58(2):336-44. doi: 10.1093/rheumatology/key069
63. Veale DJ, McGonagle D, McInnes IB, et al. The rationale for Janus kinase inhibitors for the treatment of spondyloarthritis. Rheumatology (Oxford). 2019 Feb 1;58(2):197-205. doi: 10.1093/rheumatology/key070
64. Virtanen A, Haikarainen T, Raivola J, Silvennoinen O. Selective JAKinibs: Prospects in Inflammatory and Autoimmune Diseases. BioDrugs. 2019;33(1):15-32. doi: 10.1007/s40259-019-00333-w
65. Kubo S, Nakayamada S, Sakata K, et al. Janus Kinase Inhibitor Baricitinib Modulates Human Innate and Adaptive Immune System. Front Immunol. 2018;9:1510. doi: 10.3389/fimmu.2018.01510
66. Hammitzsch A, Chen L, de Wit J, et al. Inhibiting ex-vivo Th17 responses in Ankylosing Spondylitis by targeting Janus kinases. Sci Rep. 2018;8(1):15645. doi: 10.1038/s41598-018-34026-1
67. Mease P, Hall S, Fitzgerald O, et al. Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N Engl J Med. 2017;377:1537-50. doi: 10.1056/NEJMoa1615975
68. Gladman D, Rigby W, Azevedo VF, et al. Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N Engl J Med. 2017;377:1525-36. doi: 10.1056/NEJMoa1615977
69. Nash P, Coates LC, Fleischmann R, et al. Efficacy of Tofacitinib for the Treatment of Psoriatic Arthritis: Pooled Analysis of Two Phase 3 Studies. Rheumatol Ther. 2018;5(2):567-82. doi: 10.1007/s40744-018-0131-5
70. Krueger J, Clark JD, Suarez-Farinas M, et al. Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: a randomized phase 2 study. J Allergy Clin Immunol. 2016;137:1079-90. doi: 10.1016/j.jaci.2015.12.1318
71. Bachelez H, van de Kerkof PC, Strohal R, et al. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial. Lancet. 2015;386:552-61. doi: 10.1016/S0140-6736(14)62113-9
72. Bissonnette R, Iversen L, Sofen H, et al. Tofacitinib withdrawal and retreatment in moderate-to-severe chronic plaque psoriasis: a randomized controlled trial. Br J Dermatol. 2015;172:1395-406. doi: 10.1111/bjd.13551
73. 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;76:1340-7. doi: 10.1136/annrheumdis-2016-210322
74. Maksymowych WP, Heijde DV, Baraliakos X, et al. Tofacitinib is associated with attainment of the minimally important reduction in axial magnetic resonance imaging inflammation in ankylosing spondylitis patients. Rheumatology (Oxford). 2018;57(8):1390-9. doi: 10.1093/rheumatology/key104
75. Fernandez-Clotet A, Castro-Poceiro J, Panes J. Tofacitinib for the treatment of ulcerative colitis. Expert Rev Clin Immunol. 2018;14(11):881-92. doi: 10.1080/1744666X.2018.1532291
76. Насонов ЕЛ, Абдулганиева ДИ, Файрушина ИФ. Место тофацитиниба в лечении воспалительных заболеваний кишечника. Терапевтический архив. 2019;91(2):101-8 doi: 10.26442/00403660.2019.02.000155
77. Papp K, Gordon K, Thaci D, et al. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N Engl J Med. 2018 Oct 4;379(14):1313-21. doi: 10.1056/NEJMoa1806382
78. Schett G, Elewaut D, McInnes IB, et al. How cytokine networks fuel inflammation: Toward a cytokine-based disease taxonomy. Nat Med. 2013;19:822-4. doi: 10.1038/nm.3260
79. Lubberts E. The IL-23-IL-17 axis in inflammatory arthritis. Nat Rev Rheumatol. 2015;11:415-29. doi: 10.1038/nrrheum.2015.53
80. Livshits G, Kalinkovich A. Hierarchical, imbalanced pro-inflammatory cytokine networks govern the pathogenesis of chronic arthropathies. Osteoarthritis Cartilage. 2018;26:7-17. doi: 10.1016/j.joca.2017.10.013
81. Gracey E, Dumas E, Yerushalmi M, et al. The ties that bind: skin, gut and spondyloarthritis. Curr Opin Rheumatol. 2019;31(1):62-9. doi: 10.1097/BOR.0000000000000569
82. Siebert S, Millar NL, McInnes IB. Who did IL-23p19 inhibition fail in AS: a tale of tissue, trials or translation? Ann Rheum Dis. 2018 Oct 8. doi: 10.1136/annrheumdis-2018-213654
83. Bianchi E, Rogge L. The IL-23/IL-17 pathway in chronic inflammatory disease-new insight from genetics and targeted therapies. Gen Immun. 2019;20:415-25. doi: 10.1038/s41435-019-0067-y
Рецензия
Для цитирования:
Насонов Е.Л., Коротаева Т.В., Дубинина Т.В., Лила А.М. Ингибиторы ИЛ23/ИЛ17 при иммуновоспалительных ревматических заболеваниях: новые горизонты. Научно-практическая ревматология. 2019;57(4):400-406. https://doi.org/10.14412/1995-4484-2019-400-406
For citation:
Nasonov E.L., Korotaeva T.V., Dubinina T.V., Lila A.M. IL-23/IL-17 INHIBITORS IN IMMUNOINFLAMMATORY RHEUMATIC DISEASES: NEW HORIZONS. Rheumatology Science and Practice. 2019;57(4):400-406. (In Russ.) https://doi.org/10.14412/1995-4484-2019-400-406