rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2017-536-548rsp-2437Research ArticleПРОГРЕСС В РЕВМАТОЛОГИИ В XXI ВЕКЕPROGRESS IN RHEUMATOLOGY IN THE XXI CENTURYИнновационные методы лечения артериита Такаясу: в фокусе ингибиторы интерлейкина 6. Собственный опыт применения тоцилизумаба и обзор литературыINNOVATIVE TREATMENTS FOR TAKAYASU’S ARTERITIS: A FOCUS ON INTERLEUKIN-6 INHIBITORS. THE AUTHORS’ EXPERIENCE WITH TOCILIZUMAB AND A REVIEW OF LITERATUREБекетоваТ. В.BeketovaT. V.

ведущий научный сотрудник лаборатории стандартизации терапии  ревматических заболеваний ФГБНУ НИИР им. В.А. Насоновой, канд. мед. наук

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

tvbek@rambler.ruНасоновЕ. Л.NasonovE. L.

научный руководитель ФГБНУ НИИР им. В.А. Насоновой, заведующий  кафедрой ревматологии ИПО ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М.  Сеченова» Минздрава России, академик РАН, профессор, докт. мед. наук

115522 Москва, Каширское шоссе, 34А

кафедра ревматологии Института профессионального образования

119991 Москва, ул. Трубецкая, 8, стр. 2

34A, Kashirskoe Shosse, Moscow 115522

Department of Rheumatology, Institute of Professional Education

8, Trubetskaya St., Build. 2, Moscow 119991

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой» ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава РоссииРоссияV.A. Nasonova Research Institute of Rheumatology I.M. Sechenov First Moscow State Medical University, Ministry of Health of RussiaRussian Federation201727102017555536548Copyright © Бекетова Т.В., Насонов Е.Л., 20172017Бекетова Т.В., Насонов Е.Л.Beketova T.V., Nasonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2437

Необходимость дальнейшего совершенствования методов лечения артериита Такаясу (АТ), прогресс в представлениях о механизмах заболевания и внедрение генно-инженерных биологических препаратов (ГИБП) в ревматологическую практику создали предпосылки для разработки нового направления фармакотерапии АТ с использованием ГИБП, связанных с ингибированием интерлейкина 6 (ИЛ6). Представлены два собственных наблюдения применения тоцилизумаба (ТЦЗ) при АТ осложненного течения. Проанализированы результаты лечения ТЦЗ по данным предварительных исследований у 115 больных АТ, опубликованных в 30 источниках литературы, а также результаты двойного слепого рандомизированного плацебоконтролируемого исследования (РПКИ) III фазы по изучению безопасности и эффективности ТЦЗ у 18 больных рефрактерным АТ. В одном собственном наблюдении с длительным анамнезом АТ осложненного течения контроль активности АТ и снижение дозы глюкокортикоидов в результате применения ТЦЗ способствовали благополучному течению беременности и родов. Во втором случае, с дебютом АТ и очаговым туберкулезом легких, назначение на фоне противотуберкулезных препаратов монотерапии ТЦЗ в течение 6 мес позволило контролировать АТ и добиться излечения туберкулеза. Согласно данным предварительных исследований, в результате лечения ТЦЗ ремиссия или улучшение наблюдаются у 85% больных АТ, в том числе при рефрактерном течении. В соответствии с РПКИ безрецидивная выживаемость через 6 мес поддерживающего лечения ТЦЗ выше, чем в группе плацебо (51 и 23% соответственно), но различия не достигли статистической значимости (р=0,0596). В связи с возможностью рецидива АТ у пациентов, получающих лечение ТЦЗ, целесообразно сочетать его с назначением цитостатиков, прежде всего метотрексата. Применение ингибиторов ИЛ6  следует рассматривать как потенциально эффективный и относительно безопасный  инновационный (off-label) метод лечения АТ при рефрактерном течении, непереносимости  или наличии противопоказаний к стандартной терапии, что требует дальнейшего изучения с проведением более масштабных рандомизированных клинических испытаний. Поскольку  в настоящее время не существует универсального способа визуализации, который мог бы  предоставить исчерпывающую информацию о состоянии сосудов при АТ, для  стандартизации последующих клинических исследований ГИБП требуется совершенствование методов оценки эффективности лечения АТ, при этом мониторинг активности АТ должен включать комплексную оценку клинических данных, современных лабораторных биомаркеров и инструментальных методов визуализации, в первую очередь неинвазивных.

The need for further improvement of treatments for Takayasu’s arteritis (TA), the progress in understanding the mechanisms of the disease, and the introduction of biological agents (BA) in rheumatology practice have created preconditions for developing a new TA pharmacotherapy using BA associated with interleukin 6 (IL-6) inhibition. The authors describe their two own cases of tocilizumab (TCZ) use for complicated TA. They analyze the results of TCZ treatment by the data of preliminary trials in 115 patients with TA, which have been published in 30 literature sources, as well as the results of Phase III double-blind, randomized placebo-controlled trials (RPCTs) of the safety and efficacy of TCZ in 18 patients with refractory TA. In one case with a long history of complicated TA, the control of TA activity and the reduction in the dose of glucocorticoids due to TCZ use contributed to the favorable course of pregnancy and labor. In the other case with the onset of TA and focal pulmonary tuberculosis (TB) treated with anti-TB drugs during TCZ monotherapy for 6 months could control TA and achieve TB cure. Preliminary trials showed that TCZ treatment-induced remission or improvement was observed in 85% of patients with TA, including that with a refractory course. RPCTs indicated that the relapse-free survival after 6-month maintenance treatment with TCZ was higher than that in the placebo group (51 and 23%, respectively); but the differences failed to reach statistical significance (p = 0.0596). Due to the fact that a recurrence of TA can occur in patients treated with TCZ, it is appropriate to combine this drug with cytostatic drugs, methotrexate in particular. The use of IL-6 inhibitors should be considered as a potentially effective and relatively safe innovative (off-label) treatment for refractory TA in patients with intolerance or contraindications to standard therapy, which requires further larger randomized clinical trials. Since now there is no universal imaging method that could provide comprehensive information on the status of vessels in TA; the standardization of future clinical trials of BAs requires the improvement of methods for evaluating the efficiency of treatment for TA; moreover, monitoring of disease activity should include a comprehensive assessment of clinical data, current laboratory biomarkers, and instrumental imaging techniques, primarily non-invasive ones.

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The authors declare that there are no conflicts of interest present.