Russian Journal of AllergyRussian Journal of AllergyРоссийский Аллергологический Журнал1810-88302686-682XPublishing House ABV Press139010.36691/RJA1390ReviewsНаучные обзорыResearch ArticleT2 asthma and T2-associated diseases: a consolidated approach to biological therapyТ2 астма и Т2-ассоциированные заболевания: единый подход к биологической терапииhttps://orcid.org/0000-0002-3162-2510NenashevaNatalya M.НенашеваНаталья Михайловна
Russian Federation

Head of Allergology and Immunology Department of Russian Medical Academy of Continuing Professional Education of the Ministry of Health of the Russian Federation, PhD, professor

зав. кафедрой аллергологии и иммунологии Федерального государственного бюджетного образовательного учреждения дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации, д.м.н., профессор

1444031@gmail.comFederal State Budgetary Educational Institution of Additional Professional Education Russian Medical Academy of Continuous Professional EducationРоссийская медицинская академия непрерывного профессионального образования Министерства здравоохранения Российской Федерации2910202017334492508202002092020Copyright ©; 2020, Pharmarus Print MediaCopyright ©; 2020, Фармарус Принт Медиа2020Pharmarus Print MediaФармарус Принт Медиаhttps://rusalljournal.ru/raj/article/view/1390

This article is dedicated to the main characteristics of severe bronchial asthma (SBA) and its heterogeneity. In particular, it describes T2 asthma and the role of the main cytokines involved in T2 inflammation. It focuses on the role of IL-4 and IL-13 in the pathogenesis of asthma and other T2-associated diseases, as key cytokines in the initiation and maintenance of T2 inflammation. The article presents the results of experimental studies proving that the activation of IL-4/IL-13 can cause significant hyperresponsiveness of the human airway smooth muscles and the combined blockade of the activity of these cytokines using a human monoclonal antibody against the common IL-4/13 receptor á-subunit-dupilumab-determines the clinical efficacy not only in relation to exacerbations and control of asthma symptoms, but also an improvement of the lung function and a reduction in bronchial hyperresponsiveness. When type 2 helper cells (Th2) interact with antigen-presenting cells, IL-4 and IL-13 are simultaneously released, therefore, blocking IL-4Rá is more effective than blocking each of the ligands separately, which explains the high efficacy of dupilumab not only in T2 asthma, but also other T2-associated diseases: atopic dermatitis and chronic rhinosinusitis with nasal polyps. In addition to asthma and atopic dermatitis, a new indication for dupilumab, chronic rhinosinusitis with nasal polyps, has recently been approved.

According to the recommendations of the European Academy of Allergy and Clinical Immunology (EAACI) for the biological therapy of SBA 2020, dupilumab is recommended as an add-on maintenance therapy in adults and children aged 12–17 years old with uncontrolled severe T2 asthma, including asthma with the allergic and eosinophilic phenotype, as well as mixed (when there are signs of both phenotypes) and steroid-dependent asthma. At the same time, dupilumab is well tolerated.

Настоящая статья посвящена основным характеристикам тяжелой бронхиальной астмы (ТБА) и ее гетерогенности, в частности охарактеризована Т2 астма и представлена роль основных цитокинов, формирующих Т2-воспаление. Основной акцент сделан на роли интерлейкина (ИЛ)-4 и ИЛ-13 в патогенезе БА и других Т2-ассоциированных заболеваний как ключевых цитокинов в запуске и поддержании Т2-воспаления. Представлены результаты экспериментальных исследований, доказывающих, что активация ИЛ-4/ИЛ-13 может вызывать выраженную гиперреактивность гладких мышц дыхательных путей человека, и сочетанная блокада активности этих цитокинов человеческим моноклональным антителом, нацеленным на общую á-субъединицу рецептора ИЛ-4/ИЛ-13 дупилумаба обусловливает клиническую эффективность не только в отношении обострений и контроля симптомов БА, но и улучшения функции легких и уменьшения бронхиальной гиперреактивности. При взаимодействии T-лимфоцитов хелперов 2-го типа (Th2) и антиген-презентирующих клеток высвобождаются одновременно ИЛ-4 и ИЛ-13, поэтому блокирование ИЛ-4Rá более эффективно, чем блокада каждого из лигандов по отдельности, что объясняет высокую эффективность дупилумаба не только при Т2 астме, но и других Т2-ассоциированных заболеваниях: атопическом дерматите и хроническом полипозном риносинусите. Помимо астмы и атопического дерматита недавно зарегистрировано новое показание для дупилумаба – хронический полипозный риносинусит.

Согласно рекомендациям Европейской Академии Аллергологии и Клинической Иммунологии (EAACI) по биологической терапии ТБА 2020, дупилумаб рекомендуется в качестве дополнительной поддерживающей терапии у взрослых и детей 12–17 лет с неконтролируемой тяжелой Т2 астмой, включая астму аллергического и эозинофильного фенотипа, а также сочетанную (когда присутствуют признаки того и другого фенотипа) и гормонозависимую. При этом отмечена хорошая переносимость препарата.

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