medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-16-186-196medsovet-6477Research ArticleРациональная фармакотерапияRational pharmacotherapyДупилумаб: основные аспекты применения при T2-опосредованных заболеванияхDupilumab: basic aspects and applications to T2-mediated diseaseshttps://orcid.org/0000-0003-3250-0694КурбачеваО. М.Kurbacheva3O. M.

Курбачева Оксана Михайловна, д.м.н., профессор, заведующая отделением «Бронхиальная астма»

115522, Россия, Москва, Каширское шоссе, д. 24

Oksana M. Kurbacheva, Dr. Sci. (Med.), Professor, Head of the Asthma Department

24, Kashirskoe Shosse, Moscow, 115522, Russia

kurbacheva@gmail.comhttps://orcid.org/0000-0003-1965-8446ДыневаМ. Е.DynevaM. E.

Дынева Мирамгуль Есенгельдыевна, к.м.н., младший научный сотрудник

115522, Россия, Москва, Каширское шоссе, д. 24

Miramgul E. Dyneva, Cand. Sci. (Med.), Junior Researcher

24, Kashirskoe Shosse, Moscow, 115522, Russia

amanturliva.miramgul@mail.ruhttps://orcid.org/0000-0002-3556-969XИльинаН. И.IlinaN. I.

Ильина Наталья Ивановна, д.м.н., профессор, главный врач

115522, Россия, Москва, Каширское шоссе, д. 24

Natalia I. Ilina, Dr. Sci. (Med.), Professor, Head Physician

24, Kashirskoe Shosse, Moscow, 115522, Russia

instimmun@yandex.ruГосударственный научный центр «Институт иммунологии»РоссияNational Research Center – Institute of ImmunologyRussian Federation202130102021016186196Copyright © Курбачева О.М., Дынева М.Е., Ильина Н.И., 20212021Курбачева О.М., Дынева М.Е., Ильина Н.И.Kurbacheva3 O.M., Dyneva M.E., Ilina N.I.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/6477

Высокий темп роста заболеваемости бронхиальной астмой (БА), полипозным риносинуситом (ПРС), атопическим дерматитом (АтД), эозинофильным эзофагитом и другими заболеваниями, в основе которых лежит Т2-воспаление, привел к разработке генно-инженерных препаратов, нацеленных на отдельные и специфические компоненты воспаления. Одни из ведущих позиций в патогенезе T2-опосредованных заболеваний занимают интерлейкины – ИЛ-4 и ИЛ-13, что объясняет перспективность изучения данных цитокинов для создания анти-ИЛ-4/ИЛ-13-моноклональных антител. Первым зарегистрированным иммунобиологическим препаратом, направленным против α-субъединицы рецептора ИЛ-4 (ИЛ-4Rα), общей для рецепторных комплексов ИЛ-4 и ИЛ-13, является дупилумаб – полностью человеческое моноклональное антитело. Дупилумаб блокирует передачу сигналов ИЛ-4 через рецепторы I типа (ИЛ-4Rα/γc) и общую передачу сигналов ИЛ-4 и ИЛ-13 через рецепторы II типа (ИЛ-4Rα/ИЛ-13Rα), т. к. сигнальный путь ИЛ-4/ИЛ-13/STAT6 играет решающую роль при T2-воспалении. Кроме того, ИЛ-4 и ИЛ-13 секретируются несколькими клетками и, наряду с другими Т2-цитокинами, а также при участии ИЛ-33, ИЛ-25 и TSLP (тимический стромальный лимфопоэтин) могут стимулировать клетки к их дальнейшей секреции провоспалительных цитокинов, способствуя поддержанию воспалительного процесса. В настоящее время дупилумаб изучен по меньшей мере у 3 000 пациентов при БА, АтД, ПРС и эозинофильном эзофагите, показав приемлемый профиль безопасности в плацебо-контролируемых исследованиях во всем 3В данной статье мы осветили результаты многочисленных клинических исследований и наблюдений, которые доказали эффективность и безопасность применения дупилумаба при БА, АтД, ПРС, пруриго, эозинофильном эзофагите и эозинофильной пневмонии.

The asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis (AD), eosinophilic esophagitis and other diseases based on T2-inflammation are a widespread in the world. It has led to the development of genetically engineered drugs aimed at individual and specific components of inflammation. One of the leading positions in the pathogenesis of T2-mediated diseases is occupied by interleukin (IL)-4 and IL-13, which explains the prospects of studying these cytokines for the creation of anti-IL-4/IL-13 monoclonal antibodies. The first immunobiological drug was registered to directe against the α subunit of the IL-4 receptor (IL-4Ra), common to both IL-4 and IL-4/IL-13 receptor complexes is dupilumab which is a fully human monoclonal antibody. Dupilumab targets the IL-4 receptor alpha chain (IL-4Rα), common to both IL-4R complexes: type 1 (IL-4Rα/γc; IL-4 specific) and type 2 (IL-4Rα/IL-13Rα1; IL-4 and IL-13 specific). Because the IL-4/IL-13/STAT6 signaling pathway plays a significant role in T2 inflammation. IL-4 and IL-13 are secreted by several cells and, along with other T2 cytokines, as well as with the participation of IL-33, IL-25 and TSLP can stimulate cells to further secrete pro-inflammatory cytokines, contributing to the maintenance of the inflammatory process. Currently, dupilumab has been studied in at least 3,000 patients with asthma, AD, CRSwNP and eosinophilic esophagitis. The results of investigation show an acceptable safety profile in placebo-controlled studies worldwide. In this article, we have highlighted the results of numerous clinical studies and observations that have proven the effectiveness and safety of the use of dupilumab in asthma, AD, CRSwNP, prurigo, eosinophilic esophagitis and eosinophilic pneumonia.

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