Experience with the use of glucocorticoids and netakimab in the treatment of patients with COVID-19 in outpatient settings

Goal. To study the efficacy and safety of therapy with netakimab (NTK) and the complex drug — betamethasone dipropionate + betamesone phosphate (B) in patients with COVID-19 in outpatient settings.

 Material and methods. A retrospective analysis of the treatment of 12 patients with severe new coronavirus infection who received therapy was performed simultaneously with netakimab (NTK) (the first administration at a dose of 60–120 mg, if indicated-the second administration at a dose of 60 mg) and a combined drug-betamethasone dipropionate + betamesone phosphate (B), at a dose of 2 ml official solution. Treatment was performed at 7th (95% CI [6; 10]) day from the beginning of the disease. Repeated administration of NTK was performed in older patients due to insufficient effect of stopping hyperthermia and/or hypoxemia. A comprehensive examination of patients before and after NTK + B therapy was performed, which included clinical (assessment of the severity and duration of fever, analysis of gas exchange indicators), instrumental (computed tomography of the lungs) and laboratory methods, including determination of ferritin, IL-6.

 Results. Simultaneous use of NTK + B therapy resulted in compensation of hyperthermia and/or SpO₂ > 93% 2.5 (95% CI [1; 3]) days after the first administration, a significant decrease in the level of inflammatory markers, and positive dynamics according to lung CT data. In all cases, increased respiratory support or additional antibiotic therapy, as well as hospitalization, were not required. The search for articles on the topic was carried out in the PubМed database in English and Russian, published in the period from 2001 to 2020.

1. 2019 novel coronavirus: Symptoms and treatment. The official website of the Government of Canada. [Electronic resource]. URL: https://www.canada.ca/en/public-health/services/diseases/2019-novelcoronavirus-infection/symptoms.html. Accessed June 03, 2020.

2. Centers for Disease Control and Prevention. 2019 Novel Coronavirus. [Electronic resource]. URL: https://www.cdc.gov/coronavirus/2019ncov/index.html. Accessed June 03, 2020.

3. Tkacheva O.N., Kotovskaya Yu.V., Aleksanyan L.A. et al. New coronavirus infection MERS-CoV-2 in elderly and senile patients: features of prevention, diagnosis and treatment. Agreed position of experts of the Russian Association of gerontologists and geriatricians. Cardiovascular therapy and prevention. 2020;19(3):127–150. (in Russian)

4. Order of the Ministry of health of Russia № 198н of 19.03.2020. [Electronic resource]. URL: http://publication.pravo.gov.ru/Document/View/0001202003190038. (In Russian).

5. Temporary guidelines “Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)”. Version 7 (03.06.2020). [Electronic resource]. URL: URL: http://www.consultant.ru/document/cons_doc_LAW_354163/. (in Russian)

6. Nardelli P., Londoni D. CОVID-19-associated thrombosis inflammatory status: the MicroCLOTS hypothesis and its prospects. General reanimatology. 2020;16(3):14–15. (in Russian)

7. Coronavirus: statistics by region and country. [Electronic resource]. URL: https://yandex.ru/covid19/stat. (in Russian)

8. Arutyunov G.P., Tarnovskaya E.I., Kosilov N. et al. Agreed position of experts of the Eurasian Association of therapists on the management of patients with comorbid pathology infected with SARSCov-2. Therapeutic archive. 2020;92(9):5–21. (in Russian) DOI: 10.26442/00403660.2020.09.000703.

9. Adler K.B., Fischer B.M., Wright D.T., Cohn L.A., Becker S. Interactions between respiratory epithelial cells and cytokines: relationships to lung inflammation. Ann. N. Y. Acad. Sci., 1994;725:128–145. DOI: 10.1111/j.1749-6632.1994.tb00275.x

10. D’Acquisto F., Maione F., Pederzoli-Ribeil M. From IL-15 to IL-33: the never-ending list of new players in inflammation. Is it time to forget the humble aspirin and move ahead? Biochem. Pharmacol. 2010;79:525–534. DOI: 10.1016/j.bcp.2009.09.015.

11. Marie Robert, Pierre Miossec Effects of interleukin 17 on the cardiovascular system. Autoimmun. Rev. 2017;16(9):984–991. DOI: 10.1016/j.autrev.2017.07.009.

12. Bakulev A.L., Samtsov A.V., Kubanov A.A., Khairutdinov V.R., Kohan M.M., Artemyeva A.V., Derbin S.I., Chernyaeva E.V., Ivanov R.A. Long-term efficacy and safety of netakimab in patients with moderate to severe vulgar psoriasis. Results of an open extended phase II clinical trial BCD-085-2-ext. Bulletin of dermatology and venereology. 2019;95(3):54–64. (in Russian). DOI: 10.25208/00424609-2019-95-3-54-64.

13. Gisondi P., Geat D., Pizzolato M., Girolomoni G. State of the art and pharmacological pipeline of biologics for chronic plaque psoriasis. Curr. Opin. Pharmacol. 2019;46:90–99. DOI: 10.1016/j.coph.2019.05.007.

14. Erdes Sh., Nasonov E., Kunder E., Pristrom A., Soroka N., Shesternya P., Dubinina T., Smakotina S., Raskina T., Krechikova D., Povarova T., Plaksina T., Gordeev I., Mazurov V., Reshetko O., Zonova E., Eremeeva A., Chernyaeva E., Makulova T., Ivanov R. Primary efficacy of netakimab, a novel interleukin-17 inhibitor, in the treatment of active ankylosing spondylitis in adults. Clinical Trial. Clin. Exp. Rheumatol. 2020;38(1):27–34. https://pubmed.ncbi.nlm. nih.gov/31025924/

15. Zaitsev A.A., Golukhova E.Z., Mamalyga M.L., Chernov S.A., Rybka M.M., Kryukov E.V., Klyuchnikov I.V., Semenov V.Yu., Orlov I.N. effectiveness of pulse therapy with methylprednisolone in patients with COVID-19. Clinical Microbiology and antimicrobial chemotherapy. 2020;2(22):88–91 (in Russian)

16. Rheumatology. National leadership. 2008, GEOTAR-Media. Moscow. (In Russian).

17. Huscher D, Thiele K, Gromnica-Ihle E, Hein G, Demary W, Dreher R, Zink A, Buttgereit F. Dose-related patterns of glucocorticoid-induced side effects. Ann. Rheum. Dis. 2009;68:1119–1124. DOI: 10.1136/ard.2008.092163.

18. Garcia Rodriguez LA, Hernandez-Diaz S. The risk of upper gastrointestinal complications associated with nonsteroidal anti-inflammatory drugs, glucocorticoids, acetaminophen, and combinations of these agents. Arthritis Res. 2001;3:98–101. DOI: 10.1186/ar146.

19. Zhang Y.-K., Yang H., Zhang J.-Y., Song L.-J., Fan Y.-C. Comparison of intramuscular compound betamethasone and oral diclofenac sodium in the treatment of acute attacks of gout. Int. J. Clin. Pract. 2014;68(5):633–8. DOI: 10.1111/ijcp.12359. Epub 2014 Jan 29.)

20. Snyman J.R., De Sommers K., van Wyk M., Blom M.W., Martini N.D., Steinmann M.A. Short-course, low-dose betamethasone therapy causes only marginal and transient hypothalamic-pituitary-adrenal-axis suppression. Clinical. Drug. Investigation. 2001;21:499–504.

21. Wenquan Niu, Yan Liu, Yue Qi, Zhijun Wu, Dingliang Zhu, Wei Jin. Association of interleukin-6 circulating levels with coronary artery disease: a meta-analysis implementing mendelian randomization approach. Int. J. Cardiol. 2012;157(2):243–52. DOI: 10.1016/j.ijcard.2011.12.098.