Role of tocilizumab therapy in COVID-19 patients: a systematic review
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20221599Keywords:
Corona virus disease, IL-6 receptor antagonist, Pharmacotherapy, SARS CoV 2, TocilizumabAbstract
Coronavirus disease 2019 (COVID-19) caused by the Severe acute respiratory syndrome coronavirus-2 (SARS CoV 2) virus has created a global threat to the entire human population. The medical and scientific community are striving hard to find an effective therapeutic strategy to overcome this crisis. There are few studies showing the efficacy of tocilizumab against COVID-19, but they many of them lack reliability due to their small sample size or sample population not representative of the general population. This meta-analysis aims to elucidate the role of tocilizumab in the management of COVID-19, its efficacy and safety profile. A comprehensive search of databases including PubMed, Medline, Cochrane, Lancet, Google Scholar, WHO, Embase, Elsevier and other modalities of search like website searching and citation tracking was carried out through which 1061 articles were identified. Among them, 10 articles that fitted the inclusion criteria and qualitatively good were taken up for the meta-analysis. Out of the 10 studies selected, the results of 9 studies were in favour of the efficacy of tocilizumab therapy, while 1 study was against the efficacy of tocilizumab. The result of our statistical analysis was that OR=0.5569 (95% CI; 0.2289 to 0.9332) for the effect of tocilizumab on mortality reduction in COVID-19 patients. Among critically ill patients with COVID-19, the in-hospital mortality was significantly reduced in patients treated with tocilizumab during the first 2 days of ICU admission compared to patients those who were not administered with tocilizumab in the early phase. Treatment with tocilizumab significantly reduces the mortality rate, increases the survival rate and lowers the risk of requiring invasive mechanical ventilation.
References
Vabret N, Britton GJ, Gruber C, Hegde S, Kim J, Kuksin M, et al. Immunology of COVID-19: Current State of the Science. Immunity. 2020;52(6):910-41.
Zhou F, Yu T, Du R. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054-62.
Guan W-J, Ni Z-Y, Hu Y. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708-20.
Nicastri E, D’Abramo A, Faggioni G. Coronavirus disease (COVID-19) in a paucisymptomatic patient: epidemiological and clinical challenge in settings with limited community transmission, Italy, February 2020. Euro Surveill. 2020;25:2000230.
Srikumar S, Perumal S. A systematic review of immune pathogenesis of SARS-COV-2 infection. Int J Adv Med. 2021;8:978-83.
Hennigan S, Kavanaugh A. Interleukin-6 inhibitors in the treatment of rheumatoid arthritis. Ther Clin Risk Manag 2008;4: 767–75.
Gupta S, Wang W, Hayek SS. Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19 [published correction appears in JAMA Intern Med. 2021;181(4):570.
RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637-45.
Narain S. Comparative Survival Analysis of Immunomodulatory Therapy for COVID-19 'Cytokine Storm': A Retrospective Observational Cohort Study. Northwell COVID-19 Research Consortium.
Martínez-Sanz J, Muriel A, Ron R. Effects of tocilizumab on mortality in hospitalized patients with COVID-19: a multicentre cohort study. Clin Microbiol Infect. 2021;27(2):238-43.
Ip A, Berry DA, Hansen E. Hydroxychloroquine and tocilizumab therapy in COVID-19 patients-An observational study. PLoS One. 2020;15(8):e0237693.
Gordon AC, Mouncey PR. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. N Engl J Med. 2021;384(16):1491-502.
Guaraldi G, Meschiari M, Cozzi-Lepri A. Tocilizumab in patients with severe COVID-19: a retrospective cohort study [published correction appears in Lancet Rheumatol. 2020;2(10):e591.
Biran N, Ip A, Ahn J. Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study. Lancet Rheumatol. 2020;2(10):e603-12.
Rosas IO, Bräu N, Waters M. Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia. N Engl J Med. 2021;384(16):1503-16.
Salama C, Han J, Yau L. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med. 2021;384(1):20-30.
Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses—drug discovery and therapeutic options. Nature Rev Drug Disc. 2016;15(5):327-47.
Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Møller R, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020;181(5):1036-45.
Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39:529-39.
Huang C, Wang Y, Li X. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506.
Swerdlow DI, Holmes MV, Kuchenbaecker KB. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet. 2012;379:1214-24.
Toniati P, Piva S, Cattalini M. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure. Autoimmun Rev. 2020;19(7):102568.
Guaraldi G, Meschiari M, Cozzi-Lepri A. Tocilizumab in patients with severe COVID-19. Lancet Rheumatol. 2020;2(8):e474-84.
Xu X, Han M, Li T. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad SciUSA. 2020;117(20):10970-5.
Morena V, Milazzo L, Oreni L. Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy. Eur J Intern Med. 2020;76:36-42.
Capra R, De Rossi N, Mattioli F. Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. Eur J Intern Med. 2020;76:31-5.