Рецепт. 2021; 24: 434-444
Цитокиновый шторм при коронавирусной инфекции COVID-19: опыт использования препарата тоцилизумаб
https://doi.org/10.34883/PI.2021.24.4.001Аннотация
При коронавирусной инфекции COVID-19 у части пациентов, преимущественно требующих вентиляционной поддержки, развивается цитокиновый шторм, который приводит к системному воспалительному ответу и полиорганной недостаточности. Одной из стратегий терапии цитокинового шторма является использование гуманизированных моноклональных антител к рецептору интерлейкина-6 (ИЛ-6), в частности препарата тоцилизумаб.
В исследование включен 131 госпитализированный пациент с инфекцией COVID-19, получивший препарат тоцилизумаб в дозе 8 мг/кг через 10 [9; 12] суток после начала заболевания. Пациенты были разделены на 2 группы в зависимости от достижения конечной точки: выписка пациента из стационара (95 пациентов, группа 1) или смерть (36 пациентов, группа 2).
Неблагоприятные клинические исходы при использовании препарата тоцилизумаб для лечения инфекции COVID-19 связаны с более старшим возрастом пациентов (57 [48; 62] лет в группе 1 против 63 [52; 69] лет в группе 2 (p<0,011); тяжестью поражения легких (тяжелое поражение по данным компьютерной томографии было у 37 (38,9%) пациентов группы 1 и 28 (77,8%) пациентов группы 2 (р<0,001); большей потребностью в О2 при спонтанном дыхании (7 [5,0; 10,0] л/мин в группе 1 против 12 [9,0; 15,0] л/мин в группе 2 (р<0,001); необходимостью проведения искусственной вентиляции легких (ИВЛ), более высоким уровнем ИЛ-6 (в группе 1 уровень ИЛ-6 составил 67,4 [36,4; 90,3] пг/мл против 127,0 [81,7; 339,1] пг/мл в группе 2 (р=0,002)). Через 6 суток после введения препарата тоцилизумаб по результатам рутинных лабораторных тестов (уровень лейкоцитов, лимфоцитов, соотношение нейтрофилы/лимфоциты, С-реактивный белок, креатинфосфокиназа, лактатдегидрогеназа) можно прогнозировать исход заболевания.
Список литературы
1. Tjuljandina E.V., Piskov D.A. (2019) Citokinovyj shtorm: osobennosti patogeneza, rol' v razvitii virusnoj infekcii. Literaturnyj obzor [Cytokine storm: features of pathogenesis, role in the development of viral infection. Literature review]. Sustainable development of science and education, no 1. pp. 256-260.
2. Shipilov M.V. (2013) Molekuljarnye mehanizmy “citokinovogo shtorma” pri ostryh infekcionnyh zabolevanijah [Molecular mechanisms of the "cytokine storm" in acute infectious diseases] Lechebnoe delo, no 1, pp.81-85.
3. Shimabukuro-Vornhagen A., Gödel P., Subklewe M., et al. (2018) Cytokine release syndrome. J Immunother Cancer, vol. 6, no 1, pp.56.
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7. Fajgenbaum D.C., June C.H. (2020) Cytokine Storm N Engl J Med, vol 383, pp.2255-2273
8. Tanaka T., Narazaki M., Kishimoto T. (2016). Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy, vol. 8, no 8, pp. 959–970.
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Recipe. 2021; 24: 434-444
Cytokine Storm in Coronavirus Infection COVID-19: Experience of Tocilizumab Use
https://doi.org/10.34883/PI.2021.24.4.001Abstract
A certain number of COVID-19 patients develops cytokine storm, which leads to the systemic inflammatory response and multiple organ failure. One of the strategies for this cytokine storm management is using of humanized monoclonal antibodies to interleukin-6 (IL-6) receptor, tocilizumab.
The study included 131 hospitalized patients with COVID-19 infection, who received tocilizumab (8 mg/kg) 10 [9; 12] days after the onset of disease. Patients were divided into 2 groups, depending on the outcome: discharge from the hospital (95 patients, group 1) or death (36 patients, group 2). Adverse clinical outcomes when using Tocilizumab for the COVID-19 infection are associated with older age of patient (57 [48; 62] years in the group 1 versus 63 [52; 69] years in group 2 (p<0.011). 37 (38.9%) patients in the group 1 had severe lung damage according to computer tomography versus 28 (77.8%) patients in the group 2 (p<0.001). In the 1st group, the need for O2 was lower: the flow during spontaneous breathing was 7 [5.0; 10.0] l/min versus 12 [9.0; 15.0] l/min in the 2nd group (p<0,001); and the need for mechanical ventilation was lower too. Patients in the 1st group had lower level of IL-6 – 67.4 [36.4; 90.3] pg/ml versus 127.0 [81.7; 339.1] pg/ml in the 2nd group (p=0.002).
In 6 days after tocilizumab administration, according to the results of routine laboratory tests (leukocyte, lymphocyte count, neutrophil/lymphocyte ratio, C-reactive protein, creatine kinase, lactate dehydrogenase), the outcome of the disease can be predicted.
References
1. Tjuljandina E.V., Piskov D.A. (2019) Citokinovyj shtorm: osobennosti patogeneza, rol' v razvitii virusnoj infekcii. Literaturnyj obzor [Cytokine storm: features of pathogenesis, role in the development of viral infection. Literature review]. Sustainable development of science and education, no 1. pp. 256-260.
2. Shipilov M.V. (2013) Molekuljarnye mehanizmy “citokinovogo shtorma” pri ostryh infekcionnyh zabolevanijah [Molecular mechanisms of the "cytokine storm" in acute infectious diseases] Lechebnoe delo, no 1, pp.81-85.
3. Shimabukuro-Vornhagen A., Gödel P., Subklewe M., et al. (2018) Cytokine release syndrome. J Immunother Cancer, vol. 6, no 1, pp.56.
4. Tisoncik J.R., Korth M.J., Simmons C.P., et al. (2012) Into the eye of the cytokine storm. Microbiol Mol Biol Rev., vol 76, pp. 16–32.
5. Siddall E., Khatri M., Radhakrishnan J. (2017) Capillary leak syndrome: etiologies, pathophysiology, and management. Kidney Int., vol. 92, no 1, pp. 37-46.
6. Lee D.W., Gardner R., Porter D.L., et al. (2014) Current concepts in the diagnosis and management of cytokine release syndrome Blood, vol. 124, no 2, pp. 188–195.
7. Fajgenbaum D.C., June C.H. (2020) Cytokine Storm N Engl J Med, vol 383, pp.2255-2273
8. Tanaka T., Narazaki M., Kishimoto T. (2016). Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy, vol. 8, no 8, pp. 959–970.
9. Karateev D.E., Luchihina E.L. (2019) Novye vozmozhnosti medikamentoznoj terapii revmatoidnogo artrita: fokus na sarilumab [New possibilities of drug therapy for rheumatoid arthritis: focus on sarilumab] Al'manah klinicheskoj mediciny. vol. 47, no 5, 461–469.
10. Antonov V.N., Ignatova G.L., Pribytkova O.V., et al. (2020) Opyt primenenija olokizumaba u bol'nyh COVID-19 [Experience of using olokizumab in patients with COVID-19]// Terapevticheskij arhiv, vol. 92, no 12, pp. 47-53.
11. Hermine O., Mariette X., Tharaux P.-L., et al. (2021) Effectiveness of Tocilizumab in Patients Hospitalized With COVID-19. A Follow-up of the CORIMUNO-TOCI-1 Randomized Clinical Trial. JAMA Intern Med, vol. 181, no 1, pp. 32-40.
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