medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2020-2-83-94medsovet-5525Research ArticleРЕВМАТОЛОГИЯRHEUMATOLOGYМесто таргетных синтетических препаратов в лечении ревматических заболеваний: фокус на тофацитинибThe role of targeted synthetic drugs in the treatment of rheumatic diseases: focus on tofacitinibhttps://orcid.org/0000-0002-2352-4080КаратеевД. Е.KarateevD. E.

Каратеев Дмитрий Евгеньевич, доктор медицинских наук, заведующий отделением ревматологии, профессор кафедры терапии

129110, Москва, ул. Щепкина, д. 61/2

Dmitriy E. Karateev, Dr. of Sci. (Med.), Head of Department of Rheumatology, Professor of Chair for Therapy

61/2, Schepkina St., 129110, Moscow, Russia

dekar@inbox.ruhttps://orcid.org/0000-0002-6519-1106ЛучихинаЕ. Л.LuchikhinaE. L.

Лучихина Елена Львовна, кандидат медицинских наук, ведущий научный сотрудник отделения ревматологии, доцент кафедры терапии

129110, Москва, ул. Щепкина, д. 61/2

Elena L. Luchikhina, Cand. of Sci. (Med.), Leading Researcher, Department of Rheumatology, Associate Professor of Chair for Therapy

61/2, Schepkina St., 129110, Moscow, Russia

 

eleluch@yandex.ruМосковский областной научно-исследовательский клинический институт им. М.Ф. ВладимирскогоРоссияMoscow Regional Research and Clinical InstituteRussian Federation202003032020028394Copyright © Каратеев Д.Е., Лучихина Е.Л., 20202020Каратеев Д.Е., Лучихина Е.Л.Karateev D.E., Luchikhina 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://www.med-sovet.pro/jour/article/view/5525

Лечение иммуновоспалительных ревматических заболеваний значительно продвинулось за последние десятилетия в связи с разработкой биологических препаратов, которые, однако, не лишены недостатков. К ним относится иммуногенность, парентеральный путь введения, потенциально недостаточная стабильность состава препарата. Большие надежды возлагаются на относительно новый класс таргетных синтетических иммуномодулирующих препаратов, в настоящее время в ревматологии представленный ингибиторами JAK-киназ (тофацитиниб, барицитиниб, упадацитиниб) и ингибитором фосфодиэстеразы-4 (апремиласт). Наиболее активно развивается группа ингибиторов JAK-киназ, влияющих на один из важнейших сигнальных путей иммунной системы. В это семейство входит 4 субтипа: JAK1, JAK2, JAK3 и тирозин-киназа2 (TYK2). JAK-киназы селективно связаны с цитоплазматическими доменами различных цитокиновых рецепторов, активация которых включает внутриклеточный сигнальный путь JAK-STAT (Signal Transducer and Activator of Transcription). Белки STAT отвечают за передачу сигнала более чем 50 цитокинов, гормонов и факторов роста, регулирующих ключевые процессы, такие как выживание, пролиферация и дифференцировка иммунных клеток. Наибольший опыт практического применения накоплен в отношении тофацитиниба. Этот препарат зарегистрирован в России по нескольким показаниям: ревматоидный артрит, псориатический артрит, псориаз, неспецифический язвенный колит. Исследования III фазы из серии ORAL при ревматоидном артрите и OPAL при псориатическом артрите продемонстрировали высокую эффективность тофацитиниба в различных клинических ситуациях. В рамках Российского стратегического исследования РЕМАРКА на фоне лечения тофацитинибом наблюдалась очень быстрая положительная динамика показателей активности, 68,8% больных достигли состояния низкой активности или ремиссии к 6-му месяцу наблюдения. Российское открытое многоцентровое наблюдательное исследование тофацитиниба у 101 больного ревматоидным артритом с недостаточной эффективностью базисных и биологических препаратов продемонстрировало достижение низкой активности или ремиссии у 60% больных, а также достоверное улучшение качества жизни при очень низкой частоте отмен из-за нежелательных явлений (менее 2%).

The treatment of immuno-inflammatory rheumatic diseases has advanced significantly in recent decades due to development of biological medications, which, however, are not without some weak points. They include immunogenicity, parenteral administration, and potentially insufficient stability of the composition of the drug. Great hopes are related to a relatively new class of targeted synthetic immunomodulatory drugs, currently represented in rheumatology by JAK kinase inhibitors (tofacitinib, baricitinib, upadacitinib) and phosphodiesterase 4 inhibitor (apremilast). The most actively developed group is JAK inhibitors that influence one of the most important signal pathway of immune system. This family includes 4 subtypes: JAK1, JAK2, JAK3 и tyrosine-kinase2 (TYK2). JAK-kinases selectively aggregate with cytoplasmic domains of different cytokine receptors, activation of which includes intracellular signal pathway JAK-STAT (Signal Transducer and Activator of Transcription). STAT proteins are responsible for transduction of the signals from more than 50 cytokines, hormones and growth factors that regulate key processes of survival, proliferation and differentiation of immune cells. The greatest practical experience achieved on tofacitinib. This medication approved inRussiafor several indications: rheumatoid arthritis, psoriatic arthritis, psoriasis, ulcerative colitis. Clinical trials of III phase of ORAL series in rheumatoid arthritis and OPAL series in psoriatic arthritis showed high efficacy of Tofacitinib in different clinical situations. In Russian strategic trial REMARKA after treatment with Tofacitinib very fast improvement of the signs of activity was observed, 68,8% patients achieved low disease activity or remission at 6th month of follow-up. Russian open multi-center observational study of Tofacitinib in 101 patients with rheumatoid arthritis and insufficient efficacy of basic and biologic drugs showed achievement of low disease activity or remission in 60% patients, as well as significant improvement of quality of life with a very low frequency of withdrawals due to adverse events (less than 2%).

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