COMPARATIVE EFFICACY OF METHYLPREDNISOLONE AND TOCILIZUMAB IN PATIENTS WITH A SEVERE FORM OF COVID-19
DOI:
https://doi.org/10.11603/1681-2727.2024.3.14652Keywords:
COVID-19, methylprednisolone, tocilizumabAbstract
Background. Recently, we have again noted an increase in the incidence of COVID-19. The treatment of patients with severe coronavirus infection poses a significant medical challenge.
Objectives. The purpose of this research was to compare the efficacy of standard therapy and pulses of methylprednisolone in combination with or without tocilizumab in patients with a severe form of COVID-19.
Patients and methods. In a retrospective study, the medical charts of 220 patients with a severe course of COVID-19 were reviewed. Patients were divided into four groups: those on daily methylprednisolone at a dose of 32 mg enterally; patients who received methylprednisolone pulses (500 mg daily intravenously for three consecutive days, with a subsequent change to the 32 mg of methylprednisolone daily); patients who received a single dose of 400 mg tocilizumab in combination with a 32 mg of methylprednisolone daily; patients who received a single dose of 400 mg tocilizumab in combination with methylprednisolone pulse therapy. At the end of therapy, 28-day mortality and the number of intubations in each group one week after the end of therapy were analyzed.
Results. Patients treated with a combination of tocilizumab and pulse methylprednisolone therapy had the lowest risk of death (p<0.001), OR=0.03 (95 % CI 0.01-0.16), compared to patients treated only with 32 mg of methylprednisolone.
Conclusions. Methylprednisolone pulses therapy is more effective than therapy with methylprednisolone at a daily dose of 32 mg. The combination of methylprednisolone and tocilizumab is more effective than the isolated administration of methylprednisolone. The combination of tocilizumab with methylprednisolone pulse therapy had the highest therapeutic effect.
References
Order of the Ministry of Health of Ukraine dated January 30, 2024 No. 154 “On Amendments to the Order of the Ministry of Health of Ukraine dated May 18, 2022 No. 831”. Official website of the Ministry of Health of Ukraine. https://moz.gov.ua/article/ministry-mandates/nakaz-moz-ukraini-vid-30012024--154-pro-vnesennja-zmin-do-nakazu-ministerstva-ohoroni-zdorovja-ukraini [in Ukrainian].
Quirch, M., Lee, J., & Rehman, S. (2020). Hazards of the cytokine storm and cytokine-targeted therapy in patients with COVID-19. Journal of medical Internet research, 22(8), e20193. DOI: https://doi.org/10.2196/20193
Michelozzi, P., de’Donato, F., Scortichini, M., De Sario, M., Noccioli, F., Rossi, P., & Davoli, M. (2020). Mortality impacts of the coronavirus disease (COVID-19) outbreak by sex and age: rapid mortality surveillance system, Italy, 1 February to 18 April 2020. Eurosurveillance, 25(19), 2000620. DOI: https://doi.org/10.2807/1560-7917.ES.2020.25.19.2000620
Klopfenstein, T., Gendrin, V., Kadiane-Oussou, N. D. J., Conrozier, T., Zayet, S., & HNF Hospital Tocilizumab Multidisciplinary Team. (2022). Tocilizumab in COVID-19 pneumonia: Practical proposals based on a narrative review of randomised trials. Reviews in medical virology, 32(1), e2239. DOI: https://doi.org/10.1002/rmv.2239
Li, G., Hilgenfeld, R., Whitley, R., & De Clercq, E. (2023). Therapeutic strategies for COVID-19: progress and lessons learned. Nature Reviews Drug Discovery, 22(6), 449-475. DOI: https://doi.org/10.1038/s41573-023-00672-y
Aletaha, D., Kerschbaumer, A., Kastrati, K., Dejaco, C., Dougados, M., McInnes, I. B., ... & Smolen, J. S. (2023). Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update. Annals of the rheumatic diseases, 82(6), 773-787. DOI: https://doi.org/10.1136/ard-2022-222784
Rosas, I. O., Bräu, N., Waters, M., Go, R. C., Hunter, B. D., Bhagani, S., ... & Malhotra, A. (2021). Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. New England Journal of Medicine, 384(16), 1503-1516.
Cortegiani, A., Ippolito, M., Greco, M., Granone, V., Protti, A., Gregoretti, C., ... & Cecconi, M. (2021). Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review. Pulmonology, 27(1), 52-66. DOI: https://doi.org/10.1016/j.pulmoe.2020.07.003
National Institutes of Health. (2023). COVID-19 treatment guidelines panel: Coronavirus diseases 2019 (COVID-19) treatment guidelines.
RECOVERY Collaborative Group. (2021). Dexamethasone in hospitalized patients with Covid-19. New England Journal of Medicine, 384(8), 693-704. DOI: https://doi.org/10.1056/NEJMoa2021436
Okano, H., Sakurai, R., & Yamazaki, T. (2023). Steroid Pulse Therapy as a Treatment for Patients With COVID-19 Pneumonia at an Intensive Care Unit: A Single-Center Retrospective Observational Study. Cureus, 15(3). DOI: https://doi.org/10.7759/cureus.36386
Channappanavar, R., & Perlman, S. (2017, July). Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. In Seminars in immunopathology (Vol. 39, pp. 529-539). Springer Berlin Heidelberg. DOI: https://doi.org/10.1007/s00281-017-0629-x
Chen, G., Wu, D. I., Guo, W., Cao, Y., Huang, D., Wang, H., ... & Ning, Q. (2020). Clinical and immunological features of severe and moderate coronavirus disease 2019. The Journal of clinical investigation, 130(5), 2620-2629. DOI: https://doi.org/10.1172/JCI137244
Bhimraj, A., Morgan, R. L., Shumaker, A. H., Lavergne, V., Baden, L., Cheng, V. C. C., ... & Falck-Ytter, Y. (2020). Infectious Diseases Society of America Guidelines on the treatment and management of patients with coronavirus disease 2019 (COVID-19). Clinical Infectious Diseases, ciaa478. DOI: https://doi.org/10.1093/cid/ciaa478
Shi, Y., Wang, Y., Shao, C., Huang, J., Gan, J., Huang, X., ... & Melino, G. (2020). COVID-19 infection: the perspectives on immune responses. Cell Death & Differentiation, 27(5), 1451-1454. DOI: https://doi.org/10.1038/s41418-020-0530-3
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., ... & Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet, 395(10223), 497-506. DOI: https://doi.org/10.1016/S0140-6736(20)30183-5
Yuan, M., Xu, X., Xia, D., Tao, Z., Yin, W., Tan, W., ... & Song, C. (2020). Effects of corticosteroid treatment for non-severe COVID-19 pneumonia: a propensity score-based analysis. Shock, 54(5), 638-643. DOI: https://doi.org/10.1097/SHK.0000000000001574
Fadel, R., Morrison, A. R., Vahia, A., Smith, Z. R., Chaudhry, Z., Bhargava, P., ... & Ramesh, M. S. (2020). Early short-course corticosteroids in hospitalized patients with COVID-19. Clinical Infectious Diseases, 71(16), 2114-2120. DOI: https://doi.org/10.1093/cid/ciaa601
Almeida, M. Q., & Mendonca, B. B. (2020). Adrenal insufficiency and glucocorticoid use during the COVID-19 pandemic. Clinics, 75, e2022. DOI: https://doi.org/10.6061/clinics/2020/e2022
Arlt, W., Baldeweg, S. E., Pearce, S. H., & Simpson, H. L. (2020). Endocrinology in the time of COVID-19: Management of adrenal insufficiency. European Journal of Endocrinology, 183(1), G25-G32. DOI: https://doi.org/10.1530/EJE-20-0361
Edalatifard, M., Akhtari, M., Salehi, M., Naderi, Z., Jamshidi, A., Mostafaei, S., ... & Rostamian, A. (2020). Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial. European Respiratory Journal, 56(6). DOI: https://doi.org/10.1183/13993003.02808-2020
Luo, P., Liu, Y., Qiu, L., Liu, X., Liu, D., & Li, J. (2020). Tocilizumab treatment in COVID-19: a single center experience. Journal of medical virology, 92(7), 814-818. DOI: https://doi.org/10.1002/jmv.25801
Canziani, L. M., Trovati, S., Brunetta, E., Testa, A., De Santis, M., Bombardieri, E., ... & Selmi, C. (2020). Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients. Journal of autoimmunity, 114, 102511.
Somers, E. C., Eschenauer, G. A., Troost, J. P., Golob, J. L., Gandhi, T. N., Wang, L., ... & Pogue, J. M. (2021). Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clinical Infectious Diseases, 73(2), e445-e454. DOI: https://doi.org/10.1093/cid/ciaa954
Toniati, P., Piva, S., Cattalini, M., Garrafa, E., Regola, F., Castelli, F., ... & Latronico, N. (2020). Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in Brescia, Italy. Autoimmunity reviews, 19(7), 102568. DOI: https://doi.org/10.1016/j.autrev.2020.102568
Guaraldi, G., Meschiari, M., Cozzi-Lepri, A., Milic, J., Tonelli, R., Menozzi, M., ... & Mussini, C. (2020). Tocilizumab in patients with severe COVID-19: a retrospective cohort study. The Lancet Rheumatology, 2(8), e474-e484. DOI: https://doi.org/10.1016/S2665-9913(20)30173-9
Capra, R., De Rossi, N., Mattioli, F., Romanelli, G., Scarpazza, C., Sormani, M. P., & Cossi, S. (2020). Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. European journal of internal medicine, 76, 31-35. DOI: https://doi.org/10.1016/j.ejim.2020.05.009
Richier, Q., Plaçais, L., Lacombe, K., & Hermine, O. (2021). COVID-19: encore une place pour le tocilizumab? La Revue de médecine interne, 42(2), 73-78. DOI: https://doi.org/10.1016/j.revmed.2020.11.016
Canziani, L. M., Trovati, S., Brunetta, E., Testa, A., De Santis, M., Bombardieri, E., ... & Selmi, C. (2020). Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients. Journal of autoimmunity, 114, 102511. DOI: https://doi.org/10.1016/j.jaut.2020.102511
Rosas, I. O., Bräu, N., Waters, M., Go, R. C., Hunter, B. D., Bhagani, S., ... & Malhotra, A. (2021). Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. New England Journal of Medicine, 384(16), 1503-1516. DOI: https://doi.org/10.1056/NEJMoa2028700
Flisiak, R., Flisiak-Jackiewicz, M., Rzymski, P., & Zarębska-Michaluk, D. (2023). Tocilizumab for the Treatment of COVID-19. Expert Review of Anti-infective Therapy, 21(8), 791-797. DOI: https://doi.org/10.1080/14787210.2023.2226867
Herrero, F. S., Gimeno, F. P., García, P. O., Gómez, C. F., Mochón, M. O., & Deltoro, M. G. (2021). Methylprednisolone added to tocilizumab reduces mortality in SARS-CoV-2 pneumonia: an observational study. Journal of internal medicine, 289(2), 259. DOI: https://doi.org/10.1111/joim.13145
Ramiro, S., Mostard, R. L., Magro-Checa, C., van Dongen, C. M., Dormans, T., Buijs, J., ... & Landewé, R. B. (2020). Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study. Annals of the rheumatic diseases, 79(9), 1143-1151. DOI: https://doi.org/10.1136/annrheumdis-2020-218479
Winthrop, K. L., & Mariette, X. (2020). To immunosuppress: whom, when and how? That is the question with COVID-19. Annals of the rheumatic diseases, 79(9), 1129-1131. DOI: https://doi.org/10.1136/annrheumdis-2020-218694
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 О. В. Олійник
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Journal Infectious Disease (Infektsiini Khvoroby) allows the author(s) to hold the copyright without registration
Users can use, reuse and build upon the material published in the journal but only for non-commercial purposes
This journal is available through Creative Commons (CC) License BY-NC "Attribution-NonCommercial" 4.0
