safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2022-10-1-34-47safetyrisk-253Research ArticleБЕЗОПАСНОСТЬ ФАРМАКОТЕРАПИИ ПРИ COVID-19SAFETY OF COVID-19 PHARMACOTHERAPYВопросы безопасности терапии тоцилизумабом и другими ингибиторами интерлейкиновSafety of Therapy with Tocilizumab and Other Interleukin Inhibitorshttps://orcid.org/0000-0001-5177-846XПетровВ. И.PetrovV. I.

Петров Владимир Иванович, академик РАН, д-р мед. наук, профессор. Scopus 7402843021, Web of science D-9412-2016, SPIN-код: 2224-5311, AuthorID: 148296 РИНЦ

пл. Павших Борцов, д. 1, Волгоград, 400131

Vladimir I. Petrov, Academician of RAS, Dr. Sci. (Med.), Professor. Scopus 7402843021, Web of science D-9412-2016, SPIN: 2224-5311, AuthorID: 148296

1 Pavshikh Bortsov Sq., Volgograd 400131

brain@sprintnet.ruhttps://orcid.org/0000-0002-4778-5015РязановаА. Ю.RyazanovaA. Y.

Рязанова Анастасия Юрьевна, канд. мед. наук, доцент. SPIN-код: 5255-0704, AuthorID: 632151 РИНЦ

пл. Павших Борцов, д. 1, Волгоград, 400131

Anastasia Yu. Ryazanova, Cand. Sci. (Med.), Associate Professor. SPIN: 5255-0704, AuthorID: 632151

1 Pavshikh Bortsov Sq., Volgograd 400131

nastasyakus@mail.ruhttps://orcid.org/0000-0002-1722-011XНекрасовД. А.NekrasovD. A.

Некрасов Дмитрий Александрович

пл. Павших Борцов, д. 1, Волгоград, 400131

Dmitry A. Nekrasov

1 Pavshikh Bortsov Sq., Volgograd 400131

dmitiynekrasov@mail.ruhttps://orcid.org/0000-0001-7862-3361СвинуховВ. И.SvinukhovV. I.

Свинухов Вадим Игоревич. SPIN-код: 9235-7172, AuthorID: 1050689

пл. Павших Борцов, д. 1, Волгоград, 400131

Vadim I. Svinukhov. SPIN: 9235-7172, AuthorID: 1050689

1 Pavshikh Bortsov Sq., Volgograd 400131

Sveklend@gmail.comhttps://orcid.org/0000-0002-2578-6228ПривальцеваН. С.PrivaltsevaN. S.

Привальцева Наталья Сергеевна. SPIN-код: 3615-3650

пл. Павших Борцов, д. 1, Волгоград, 400131

Natalia S. Privaltseva. SPIN: 3615-3650

1 Pavshikh Bortsov Sq., Volgograd 400131

nata.privalceva@yandex.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияVolgograd State Medical UniversityRussian Federation2022310120221013447Copyright © Петров В.И., Рязанова А.Ю., Некрасов Д.А., Свинухов В.И., Привальцева Н.С., 20222022Петров В.И., Рязанова А.Ю., Некрасов Д.А., Свинухов В.И., Привальцева Н.С.Petrov V.I., Ryazanova A.Y., Nekrasov D.A., Svinukhov V.I., Privaltseva N.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/253

Моноклональные антитела к интерлейкинам и их рецепторам с 2001 г. успешно применяют для лечения ревматологических заболеваний, а с 2020 г. используют в составе комплексной терапии пациентов с тяжелым течением COVID-19. В связи с этим представляют интерес вопросы безопасности терапии препаратами данной группы, в том числе по показаниям, по которым они ранее не применялись. Цель работы: анализ информации о возможных нежелательных реакциях при применении тоцилизумаба и других ингибиторов интерлейкинов для повышения безопасности фармакотерапии пациентов с системными заболеваниями соединительной ткани, а также пациентов с тяжелым течением COVID-19. По данным литературы наиболее частыми нежелательными реакциями при применении тоцилизумаба и других ингибиторов интерлейкинов являются инфекционные осложнения, гиперхолестеринемия, лейкопения, нейтропения, тромбоцитопения и повышение активности печеночных ферментов. Серьезную угрозу для жизни представляют также реакции гиперчувствительности и острые инфузионные реакции, протекающие по типу псевдоаллергических реакций. Однако выявление нежелательных реакций ингибиторов интерлейкинов затруднено, поскольку препараты этой группы применяют длительно с большими интервалами между введениями. Кроме того, их часто используют в комбинации с другими лекарственными средствами (например, метотрексатом, глюкокортикостероидами), что не всегда позволяет достоверно соотнести развитие нежелательной реакции с применением конкретного препарата. Безопасность применения тоцилизумаба и других ингибиторов интерлейкинов в комплексной терапии пациентов с тяжелым течением COVID-19 в настоящее время изучена недостаточно, поэтому необходимо продолжение ее исследования с увеличением числа участников и взвешенным анализом отношения ожидаемой пользы к возможному риску применения этих препаратов при данном заболевании.

Monoclonal antibodies directed against interleukin and interleukin receptors have been successfully used for the treatment of rheumatic diseases since 2001, and since 2020 they have been used as part of complex therapy for patients with severe COVID-19. This raises the question of safety of these products, especially when used for new indications. The aim of the study was to analyse data on potential adverse reactions to tocilizumab and other interleukin inhibitors in order to increase the safety of pharmacotherapy of systemic connective tissue diseases, as well as of severe COVID-19. Literature data suggest that the most frequent adverse reactions to tocilizumab and other interleukin inhibitors are infections, hypercholesterolemia, leukopenia, neutropenia, thrombocytopenia, and increased liver enzyme activity. Hypersensitivity and acute infusion reactions, manifested as pseudoallergic reactions, also pose serious health risks and can even be fatal. However, the identification of undesirable reactions to interleukin inhibitors is challenging, due to their prolonged intake and long intervals between injections. Besides, they are often used in combination with other medicines, such as methotrexate or glucocorticosteroids, which complicates establishment of a reliable correlation between an adverse reaction and a particular medicine. At present, the safety of tocilizumab and other interleukin inhibitors for the treatment of severe COVID-19 has not been studied properly and needs further research with an increased number of participants and a careful analysis of the risk/benefit ratio of these medicines when used for COVID-19 treatment.

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