Consilium MedicumConsilium MedicumConsilium MedicumConsilium Medicum2075-17532542-2170Consilium Medicum9513910.26442/20751753.2018.12.000047ArticlesСтатьиReview ArticleCurrent therapy of primary systemic vasculitisВозможности современной терапии первичных системных васкулитовZykovaA. SЗыковаАнастасия Сергеевна

аспирант каф. внутренних болезней

ansezy@gmail.comSchegolevaE. MЩеголеваЕлена Маратовна

врач-ревматолог ревматологического отд-ния Университетской клинической больницы №3

BulanovN. MБулановНиколай Михайлович

канд. мед. наук, ассистент каф. внутренних, профессиональных болезней и ревматологии

NovikovP. IНовиковПавел Игоревич

канд. мед. наук, зав. ревматологическим отд-нием Университетской клинической больницы №3

MoiseevS. VМоисеевСергей Валентинович

д-р мед. наук, проф., зав. каф. внутренних, профессиональных болезней и ревматологии; проф. каф. внутренних болезней

M.V.Lomonosov Moscow State UniversityФГБОУ ВО «Московский государственный университет им. М.В.Ломоносова»I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian FederationФГАОУ ВО «Первый Московский государственный университет им. И.М.Сеченова» Минздрава России151220182012VOL 20, NO12 (2018)ТОМ 20, №12 (2018)869328122021Copyright ©; 2018, Consilium MedicumCopyright ©; 2018, ООО "Консилиум Медикум"2018Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://consilium.orscience.ru/2075-1753/article/view/95139

Systemic vasculitis is a group of rare diseases characterized by unfavorable prognosis without correct therapy. Today survival rate in this patient increased due to usage of modern immunosuppressive therapy (IST) which consists of combinations of glucocorticosteroids, cytostatic agents and biological drugs. Unfortunately, its use can also be associated with development of serious complications. The review discusses the basic IST regimen of vasculitis treatment their complexity and perspectives

Системные васкулиты - редкая группа заболеваний, характеризующаяся неблагоприятным прогнозом без корректно подобранной терапии. Иммуносупрессивная терапия (ИСТ), представляющая собой комбинации глюкокортикостероидов и цитостатиков, а теперь и генно-инженерных биологических препаратов, повышает выживаемость при данных заболеваниях, однако может быть ассоциирована с развитием грозных осложнений. В обзоре обсуждаются основные схемы ИСТ, применяемые в лечении системных васкулитов, поражающих мелкие и крупные сосуды, текущие сложности и перспективы такого лечения.

giant cell arteritisTakayasu diseaseANCA associated vasculitisHCV-associated cryoglobulinemic vasculitisclinical studiesгигантоклеточный артериитартериит ТакаясуАНЦА-ассоциированные васкулитыHCV-ассоциированный криоглобулинемический васкулитклинические исследованияJennette J. Overview of the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Clin Exp Nephrol 2013; 17 (5): 603-6. DOI: 10.1007/s10157-013-0869-6Новиков П.И., Семенкова Е.Н., Моисеев С.В. Современная номенклатура системных васкулитов. Клин. фармакология и терапия. 2013; 22 (1): 70-4.Мухин Н.А., Розина Т.П, Новиков П.И. и др. Узелковый полиартериит, ассоциированный с вирусом гепатита В (клинический разбор). Клин. медицина. 2015; 93 (6): 5-13.Игнатова Т.М., Чернова О.А., Бурневич Э.З., Милованова С.Ю. Успешное лечение HCV-криоглобулинемического васкулита тяжелого течения с помощью CD-20 моноклональных антитела и противовирусных препаратов. Клин. медицина. 2014; 92 (8): 62-4.Mukhtyar C, Guillevin L, Cid M et al. EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis 2009; 68 (3): 318-23. DOI: 10.1136/ard.2008.088351Мухин Н.А., Мешков А.Д., Новиков П.И. и др. Гигантоклеточный артериит: клинические проявления и методы ранней диагностики. Клин. фармакология и терапия. 2015; 24 (3): 79-85.Мухин Н.А., Смитиенко И.О., Новиков П.И. и др. Такаясу: трудности диагностики, лечение и исходы в когортном исследовании у 128 больных. Клин. фармакология и терапия. 2014; 23 (3): 55-61.Kotter I, Henes J, Wagner A et al. Does glucocorticosteroid-resistant large-vessel vasculitis (giant cell arteritis and Takayasu arteritis) exist and how can remission be achieved? A critical review of the literature. Clin Exp Rheumatol 2012; 30 (1; Suppl. 70): 114-29.Bienvenu B, Ly K, Lambert M et al. Management of giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis (GEFA). La Revue de Médecine Interne 2016; 37 (3): 154-65. DOI: 10.1016/j.revmed.2015.12.015Seror R, Baron G, Hachulla E et al. Adalimumab for steroid sparing in patients with giant-cell arteritis: results of a multicentre randomised controlled trial. Ann Rheum Dis 2014; 73 (12): 2074-81. DOI: 10.1136/annrheumdis-2013-203586Hoffman G, Cid M, Rendt-Zagar K et al. Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis: a randomized trial. Ann Int Med 2007; 146 (9): 621-30.Martínez-Taboada V, Rodríguez-Valverde V, Carreño L et al. A double-blind placebo controlled trial of etanercept in patients with giant cell arteritis and corticosteroid side effects. Ann Rheum Dis 2008; 67 (5): 625-30.Loricera J, Blanco R, Hernández J et al. Tocilizumab in giant cell arteritis: Multicenter open-label study of 22 patients. Semin Arthr Rheum 2015; 44 (6): 717-23. DOI: 10.1016/j.semarthrit.2014.12.005Régent A, Redeker S, Deroux A et al. Tocilizumab in Giant Cell Arteritis: A Multicenter Retrospective Study of 34 Patients. J Rheumatol 2016; 43 (8): 1547-52. DOI: 10.3899/jrheum.151252Villiger P, Adler S, Kuchen S et al. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet 2016; 387 (10031): 1921-7. DOI: 10.1016/S0140-6736(16)00560-2Сатыбалдыев А.М., Сатыбалдыева М.А., Насонов Е.Л. Тоцилизумаб в лечении ревматической полимиалгии и гигантоклеточного артериита. Клин. фармакология и терапия. 2017; 26 (1): 47-53Stone J, Tuckwell K, Dimonaco S et al. Efficacy and Safety of Tocilizumab in Patients with Giant Cell Arteritis: Primary and Secondary Outcomes from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial. Paper presented at: ACR/ARHP 2016 Annual Meeting. November 13, 2016. Available at: http://acrabstracts.org/abstract/efficacy-and-safety-of-tocilizumab-in-patients-with-giant-cell-arte.. Accessed March 27, 2017.Conway R, O'Neill L, O'Flynn E et al. Ustekinumab for the treatment of refractory giant cell arteritis. Ann Rheum Dis 2016; 75 (8): 1578-9. DOI: 10.1136/annrheumdis-2016-209351Hoffman G, Merkel P, Brasington R et al. Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis. Arthritis Rheum 2004; 50 (7): 2296-304. DOI: 10.1002/art.20300Comarmond C, Plaisier E, Dahan K et al. Anti TNF-alpha in refractory Takayasu's arteritis: cases series and review of the literature. Autoimmunity Rev 2012; 11 (9): 678-84. DOI: 10.1016/j.autrev.2011.11.025Новиков П.И., Смитиенко И.О., Моисеев С.В. Эффективность продолжительного лечения ингибиторами фактора некроза опухоли-a при артериите Такаясу, рефрактерном к стандартной иммуносупрессивной терапии. Клин. фармакология и терапия. 2013; 22 (2): 44-8.Novikov P, Smitienko I, Moiseev S. Tumor necrosis factor alpha inhibitors in patients with Takayasu's arteritis refractory to standard immunosuppressive treatment: cases series and review of the literature. Clin Rheumatol 2013; 32 (12): 1827-32. DOI: 10.1007/s10067-013-2380-6Loricera J, Blanco R, Hernandez J et al. Tocilizumab in patients with Takayasu arteritis: a retrospective study and literature review. Clin Exp Rheumatol 2016; 34 (3; Suppl. 97): 44-53.Park M, Lee S, Park Y, Lee S. Serum cytokine profiles and their correlations with disease activity in Takayasu's arteritis. Rheumatology 2006; 45 (5): 545-8. DOI: 10.1093/rheumatology/kei266Nishimoto N, Nakahara H, Yoshio-Hoshino N, Mima T. Successful treatment of a patient with Takayasu arteritis using a humanized anti-interleukin-6 receptor antibody. Arthritis Rheum 2008; 58 (4): 1197-200. DOI: 10.1002/art.23373Mekinian A, Comarmond C, Resche-Rigon M et al. Efficacy of Biological-Targeted Treatments in Takayasu Arteritis: Multicenter, Retrospective Study of 49 Patients. Circulation 2015; 132 (18): 1693-700. DOI: 10.1161/circulationaha.114.014321Langford C, Cuthbertson D, Ytterberg S et al. A randomized, double-blind trial of abatacept (CTLA4-ig) for the treatment of Takayasu's arteritis. Arthritis Rheum 2017. DOI: 10.1002/art.40037O’Connor T, Carpenter H, Bidari S et al. Role of inflammatory markers in Takayasu arteritis disease monitoring. BMC Neurology 2014; 14: 62. DOI: 10.1186/1471-2377-14-62Smitienko I, Atyasova E, Moiseev S, Novikov P. MR Angiography for Evaluation of Vascular Inflammation in Patients with Takayasu's Arteritis. Paper presented at: The 18th Inernational Vasculitis and ANCA Workshop. March 25-28, 2017. Available at: http://www.anca2017.tokyo/abstracts.html. Accessed March 27, 2017.Nakagomi D, Jayne D. Outcome assessment in Takayasu arteritis. Rheumatology (Oxford) 2016; 55 (7): 1159-71. DOI: 10.1093/rheumatology/kev366Goglin S, Chung S. Current Treatment of Cryoglobulinemic Vasculitis. Curr Treat Options Rheumatol 2016; 2 (2): 213-24. DOI: 10.1007/s40674-016-0048-5Ferri C, Greco F, Longombardo G et al. Association between hepatitis C virus and mixed cryoglobulinemia [see comment]. Clin Exp Rheumatol 1991; 9 (6): 621-4.Милованова C.Ю., Козловская Л.В., Гордовская Н.Б. Полиморфизм клинических проявлений риоглобулинемического васкулита, ассоциированного с хроническим гепатитом С. Альманах клинической медицины. 2014; 30: 46-51. DOI: 10.18786/2072-0505-2014-30-46-51Ignatova T, Chernova O, Novikov P, Moiseev S. HCV-associated cryoglobulinaemic vasculitis: triple/dual antiviral treatment and/or rituximab? Ann Rheum Dis 2014; 73 (9): e58. DOI: 10.1136/annrheumdis-2014-205997Saadoun D, Thibault V, Si Ahmed S et al. Sofosbuvir plus ribavirin for hepatitis C virus-associated cryoglobulinaemia vasculitis: VASCUVALDIC study. Ann Rheum Dis 2016; 75 (10): 1777-82. DOI: 10.1136/annrheumdis-2015-208339Ferri C, Giuggioli D, Cazzato M et al. HCV-related cryoglobulinemic vasculitis: an update on its etiopathogenesis and therapeutic strategies. Clin Exp Rheum 2003; 21 (6; Suppl. 32): 78-84.De Vita S, Quartuccio L, Isola M et al. A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis. Arthritis Rheum 2012; 64 (3): 843-53. DOI: 10.1002/art.34331Saadoun D, Resche Rigon M, Pol S et al. PegIFNalpha/ribavirin/protease inhibitor combination in severe hepatitis C virus-associated mixed cryoglobulinemia vasculitis. J Hepatol 2015; 62 (1): 24-30. DOI: 10.1016/j.jhep.2014.08.015Saadoun D, Thibault V, Si Ahmed S et al. Sofosbuvir plus ribavirin for hepatitis C virus-associated cryoglobulinaemia vasculitis: VASCUVALDIC study. Ann Rheum Dis 2016; 75 (10): 1777-82. DOI: 10.1136/annrheumdis-2015-208339Bonacci M, Lens S, Londoño M et al. Virologic, Clinical, and Immune Response Outcomes of Patients With Hepatitis C Virus Associated Cryoglobulinemia Treated With Direct-Acting Antivirals. Clin Gastroenterol Hepatol 2017; 15 (4): 575-83. DOI: 10.1016/j.cgh.2016.09.158Saadoun D, Pol S, Ferfar Y et al. Sofosbuvir plus daclatasvir for hepatitis C virus-cryoglobulinemia vasculitis (HCV-CryoVas): VASCUVALDIC 2 Study. J Hepatol 2017; 66 (1): 56. doi.org/10.1016/S0168-8278(17)30375-6Mukhtyar C, Flossmann O, Hellmich B et al. Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force. Ann Rheum Dis 2008; 67 (7): 1004-10. DOI: 10.1136/ard.2007.071936Flossmann O, Berden A, de Groot K et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis 2011; 70 (3): 488-94. DOI: 10.1136/ard.2010.137778Novikov P, Moiseev S, Kuznetsova E et al. Changing patterns of clinical severity and risk of mortality in granulomatosis with polyangiitis over four decades: the Russian experience. Rheumatol Int 2015; 35 (5): 891-8. DOI: 10.1007/s00296-014-3154-4Hoffman G, Kerr G, Leavitt R et al. Wegener granulomatosis: an analysis of 158 patients. Ann Int Med 1992; 116 (6): 488-98. DOI: 10.7326/0003-4819-116-6-488Faurschou M, Sorensen I, Mellemkjaer L et al. Malignancies in Wegener's granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J Rheumatol 2008; 35 (1): 100-5.de Groot K, Harper L, Jayne D et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med 2009; 150 (10): 670-80. DOI: 10.7326/0003-4819-150-10-200905190-00004Harper L, Morgan M, Walsh M et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann Rheum Dis 2012; 71 (6): 955-60. DOI: 10.1136/annrheumdis-2011-200477Jayne D, Rasmussen N, Andrassy K et al. A Randomized Trial of Maintenance Therapy for Vasculitis Associated with Antineutrophil Cytoplasmic Autoantibodies. N Engl J Med 2003; 349 (1): 36-44. DOI: 10.1056/NEJMoa020286Stone J, Merkel P.A, Spiera R et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010; 363 (3): 221-32. DOI: 10.1056/NEJMoa0909905Jones R, Tervaert J, Hauser T et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 2010; 363 (3): 211-20. DOI: 10.1056/NEJMoa0909169Yates M, Watts R, Bajema I et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 2016; 75 (9): 1583-94. DOI: 10.1136/annrheumdis-2016-209133Новиков П.И., Зыкова А.С., Смитиенко И.О., Моисеев С.В. Лечение АНЦА-ассоциированных васкулитов: рекомендации EULAR\ERA-EDTA 2016 года. Клин. фармакология и терапия. 2017; 26 (1): 80-7.Guillevin L, Pagnoux C, Karras A et al. Rituximab versus Azathioprine for Maintenance in ANCA-Associated Vasculitis. N Engl J Med 2014; 371 (19): 1771-80. DOI: 10.1056/NEJMoa1404231Бекетова Т.В., Александрова Е.Н., Новоселова Т.М. и др. Российский опыт применения моноклональных антител к В-лимфоцитам (Ритуксимаб) при системных васкулитах, ассоциированных с антинейтрофильными цитоплазматическими антителами (предварительные результаты российского регистра НОРМА). Научно-практическая ревматология. 2014; 52 (2): 147-58. DOI: 10.14412/1995-4484-2014-147-158Ананьева Л.П., Соловьев С.К., Бекетова Т.В. и др. Анти-В-клеточная терапия при иммуновоспалительных ревматических заболеваниях: эффективность и переносимость у 229 больных. Научно-практическая ревматология. 2014; 52 (5): 495-506. DOI: 10.14412/1995-4484-2014-495-506Novikov P, Moiseev S, Shevtsova T, Smitienko I. Short-term Efficacy and Safety of Biosimilar Rituximab in Patients with Systemic Vasculitides. Paper presented at: The 18th Inernational Vasculitis and ANCA Workshop. March 25-28, 2017. Available at: http://www.anca2017.tokyo/abstracts.html. Accessed March 27, 2017Walsh M, Merkel P, Peh C et al. Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial. Trials 2013; 14: 3. DOI: 10.1186/1745-6215-14-73Charles P, Terrier B, Perrodeau E et al. Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2). Ann Rheum Dis 2018; 77 (8): 1143-9. DOI: 10.1136/annrheumdis-2017-212878Lenert A, Lenert P. Current and emerging treatment options for ANCA-associated vasculitis: potential role of belimumab and other BAFF/APRIL targeting agents. Drug Design Development Ther 2015; 9: 333-47. DOI: 10.2147/DDDT.S67264Mackay F, Schneider P, Rennert P, Browning J. BAFF and APRIL: a tutorial on B cell survival. Ann Rev Immunol 2003; 21: 231-64. DOI: 10.1146/annurev.immunol.21.120601.141152Schiemann B, Gommerman J, Vora K et al. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science 2001; 293 (5537): 2111-4. DOI: 10.1126/science.1061964Bamberg C, Mackay C, Lee H et al. The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction. J Biol Chem 2010; 285 (10): 7633-44. DOI: 10.1074/jbc.M109.092106Jayne D, Bruchfeld A, Harper L et al. MO039Successful steroid replacement in ANCA-associated vasculitis with C5A receptor inhibitor CCX168 in phase 2 randomised (CLEAR). Nephrol Dial Transplant 2016; 31 (Suppl. 1): 45. DOI: 10.1093/ndt/gfw137.01Merkel P.A, Niles J, Jimenez R et al. A Randomized Clinical Trial of CCX168, an Orally Administered C5aR Inhibitor for Treatment of Patients with ANCA-Associated Vasculitis [abstract]. Arthritis Rheumatol 2016; 68 (Suppl. 10). Paper presented at: 2016 ACR/ARHR Annual Meeting. November 13, 2016. Available at: http://acrabstracts.org/abstract/a-randomized-clinical-trial-of-ccx168-an-orally-administered-c5ar-i.. March 27, 2017.Puéchal X, Pagnoux C, Baron G et al. Prevent relapses in patients with systemic necrotizing vasulitides without poor-prognosis factors? A multicenter, double-blind randomized controlled trial. Ann Rheum Dis 2016; 75 (Suppl. 2): 77. DOI: 10.1136/annrheumdis-2016-eular.6204Moiseev S, Novikov P. Five Factor Score in patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss; EGPA): to use or not to use? Ann Rheum Dis 2014; 73 (3)e. 12. DOI: 10.1136/annrheumdis-2013-204809Mohammad A, Hot A, Arndt F et al. Rituximab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Ann Rheum Dis 2016; 75: 396-401. DOI: 10.1136/annrheumdis-2014-206095Novikov P, Moiseev S, Smitienko I, Zagvozdkina E. Rituximab as induction therapy in relapsing eosinophilic granulomatosis with polyangiitis: A report of 6 cases. Joint, bone, spine 2016; 83 (1): 81-4. DOI: 10.1016/j.jbspin.2015.04.016Novikov P, Moiseev S. Biologic therapy for eosinophilic granulomatosis with polyangiitis: comment on the article by Jachiet et al. Arthritis Rheumatol 2016. DOI: 10.1002/art.40015Jachiet M, Samson M, Cottin V et al. Anti-IgE Monoclonal Antibody (Omalizumab) in Refractory and Relapsing Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss): Data on Seventeen Patients. Arthritis Rheumatol 2016; 68 (9): 2274-82. DOI: 10.1002/art.39663