https://doi.org/10.4081/monaldi.2022.2136
Tocilizumab for COVID-19: A systematic review and meta-analysis of randomized controlled trials
Submitted: October 24, 2021
Accepted: January 17, 2022
Published: February 4, 2022
Accepted: January 17, 2022
Abstract Views: 2108
PDF: 985
Supplementary: 207
Supplementary: 207
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
The effective treatment modalities for severe coronavirus disease 2019 (COVID-19) are needed. As the primary cause of mortality is a hyperinflammatory state, the interleukin-6 antagonist tocilizumab has been used in multiple clinical studies. We conducted this systematic review and meta-analysis to estimate the effectiveness of tocilizumab in reduction of mortality due to COVID-19. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of tocilizumab therapy for COVID-19. An overall pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Nine RCTs, including 6489 patients, were selected for meta-analysis. Seven trials reported 28-day mortality, and one trial each reported 21-day and 30-day mortality. There were 846 deaths among 3358 participants in the steroid group while 943 deaths among 3131 patients randomized to the control group (random-effects odds ratio 0.87, 95% confidence interval 0.73-1.03, p=0.11). There was some heterogeneity among the trials as the I2 value was 15%, with a p-value of 0.31. There was a reduction in the need for ICU admission in the tocilizumab group. A higher risk of secondary infections was noted in the tocilizumab group (fixed-effects odds ratio 0.72, 95% confidence interval 0.55-0.95, p=0.02). This meta-analysis of RCTs demonstrated that the use of tocilizumab was not associated with a reduction in all-cause mortality in patients with COVID-19 and had higher odds of secondary infections.
Aggarwal N, Boppana TK, Mittal S. COVID-19 pandemic: The testing times for healthcare workers. Monaldi Arch Chest Dis 2021;91:1515.
DOI: https://doi.org/10.4081/monaldi.2021.1515
Sehgal IS, Guleria R, Singh S, et al. A randomised trial of Mycobacterium w in critically ill patients with COVID-19: ARMY-1. ERJ Open Research 2021;7:00059-2021.
DOI: https://doi.org/10.1183/23120541.00059-2021
Boppana TK, Mohan A, Madan K, et al. Candidate immunomodulators for COVID-19: Heat-killed Mycobacterium w and BCG vaccine. Adv Respir Med 2021;89:350–1.
DOI: https://doi.org/10.5603/ARM.a2021.0043
Sryma PB, Mittal S, Madan K, et al. Reinventing the wheel in ARDS: Awake proning in COVID-19. Arch Bronconeumol 2020;56:747–9.
DOI: https://doi.org/10.1016/j.arbres.2020.06.002
Sryma P, Mittal S, Madan K, et al. Awake prone positioning in non-intubated patients for the management of hypoxemia in COVID-19: A systematic review and meta-analysis. Monaldi Arch Chest Dis 2021;91:1623.
DOI: https://doi.org/10.4081/monaldi.2021.1623
Li P, Lu Z, Li Q, et al. Administration timing and efficacy of tocilizumab in patients With COVID-19 and elevated IL-6. Front Mol Biosci 2021;8:651662.
DOI: https://doi.org/10.3389/fmolb.2021.651662
Gritti G, Raimondi F, Bottazzi B, et al. Siltuximab downregulates interleukin-8 and pentraxin 3 to improve ventilatory status and survival in severe COVID-19. Leukemia 2021;2710-4
DOI: https://doi.org/10.1038/s41375-021-01299-x
Corominas H, Castellví I, Diaz-Torné C, et al. Sarilumab (IL-6R antagonist) in critically ill patients with cytokine release syndrome by SARS-CoV2. Medicine (Baltimore) 2021;100:e25923.
DOI: https://doi.org/10.1097/MD.0000000000025923
RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021;397:1637–45.
DOI: https://doi.org/10.1016/S0140-6736(21)00676-0
Hermine O, Mariette X, Tharaux P-L, et al. Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: A randomized clinical trial. JAMA Intern Med 2021;181:32–40.
Salama C, Han J, Yau L, et al. Tocilizumab in patients hospitalized with Covid-19 pneumonia. N Engl J Med 2021;384:20–30.
DOI: https://doi.org/10.1056/NEJMoa2030340
Salvarani C, Dolci G, Massari M, et al. Effect of tocilizumab vs standard care on clinical worsening in patients hospitalized with COVID-19 pneumonia: A randomized clinical trial. JAMA Intern Med 2021;181:24–31.
DOI: https://doi.org/10.1001/jamainternmed.2020.6615
Elavarasi A, Sahoo RK, Seth T, et al. Anti-interleukin-6 therapies for Covid-19: A systematic review, critical appraisal and meta-analysis. Natl Med J India 2020;33:152–7.
DOI: https://doi.org/10.4103/0970-258X.288119
Cortegiani A, Ippolito M, Einav S. Rationale and evidence on the use of tocilizumab in COVID-19: A systematic review. Pulmonology 2021;27:52-66.
DOI: https://doi.org/10.1016/j.pulmoe.2020.07.003
Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009;339:b2700–b2700.
DOI: https://doi.org/10.1136/bmj.b2700
Mariette X, Hermine O, Tharaux P-L, et al. Effectiveness of tocilizumab in patients hospitalized with COVID-19: A follow-up of the CORIMUNO-TOCI-1 randomized clinical trial. JAMA Intern Med 2021;181:1241–3.
DOI: https://doi.org/10.1001/jamainternmed.2021.2209
Zhao H, Zhu Q, Zhang C, et al. Tocilizumab combined with favipiravir in the treatment of COVID-19: A multicenter trial in a small sample size. Biomed Pharmacother 2021;133:110825.
DOI: https://doi.org/10.1016/j.biopha.2020.110825
Gordon AC, Mouncey PR, Al-Beidh F et al. Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N Engl J Med 2021;384:1491–502.
DOI: https://doi.org/10.1056/NEJMoa2100433
Soin AS, Kumar K, Choudhary NS, et al. Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): an open-label, multicentre, randomised, controlled, phase 3 trial. Lancet Respir Med 2021;9:511–21.
DOI: https://doi.org/10.1016/S2213-2600(21)00081-3
Rosas IO, Bräu N, Waters M, et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med 2021;384:1503–16.
DOI: https://doi.org/10.1056/NEJMoa2028700
Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med 2020;383:2333–44.
DOI: https://doi.org/10.1056/NEJMoa2028836
Veiga VC, Prats JAGG, Farias DLC, et al. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. BMJ 2021;372:n84.
DOI: https://doi.org/10.1136/bmj.n84
WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: A meta-analysis. JAMA 2020;324:1330-41.
DOI: https://doi.org/10.1001/jama.2020.17023
Mittal S, Madan K, Mohan A, et al. Diabetes in COVID-19: Steroid effect. J Med Virol 2021;93:4166.
DOI: https://doi.org/10.1002/jmv.26457
Oliynyk O, Barg W, Slifirczyk A, et al. Efficacy of tocilizumab therapy in different subtypes of COVID-19 cytokine storm syndrome. Viruses 2021;13:1067.
DOI: https://doi.org/10.3390/v13061067
Rosas IO, Diaz G, Gottlieb RL, et al. Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial. Intensive Care Med 2021;47:1258-70.
DOI: https://doi.org/10.1007/s00134-021-06507-x
Hamed DM, Belhoul KM, Al Maazmi NA, et al. Intravenous methylprednisolone with or without tocilizumab in patients with severe COVID-19 pneumonia requiring oxygen support: A prospective comparison. J Infect Public Health 2021;14:985-9.
DOI: https://doi.org/10.1016/j.jiph.2021.06.003
Declercq J, Van Damme KFA, De Leeuw E, et al. Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial. Lancet Respir Med 2021;9:1427-38.
DOI: https://doi.org/10.1016/S2213-2600(21)00377-5
How to Cite
Boppana, Tarun Krishna, Saurabh Mittal, Karan Madan, Anant Mohan, Vijay Hadda, and Randeep Guleria. 2022. “Tocilizumab for COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials”. Monaldi Archives for Chest Disease 92 (4). https://doi.org/10.4081/monaldi.2022.2136.
Copyright (c) 2022 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Danilo Buonsenso, Davide Pata, Chiara Rocchetti, Giampietro Marchetti, Stefano Elia, Camillo Il Grande, Piero Valentini, Guido Levi, Research data communication strategy at the time of pandemics: a retrospective analysis of the Italian experience , Monaldi Archives for Chest Disease: Vol. 92 No. 1 (2022)
- Taymmia Ejaz, Mahmood Iqbal Malik, Jamal Ahmed, Rizwan Azam, Yousaf Jamal, Sheema Saadia, Clinico-radiological and bronchoscopic predictors of microbiological yield in sputum negative tuberculosis in Pakistan , Monaldi Archives for Chest Disease: Vol. 92 No. 3 (2022)
- Manu Dogra, Surabhi Jaggi, Deepak Aggarwal, Seema Gupta, Varinder Saini, Jasbinder Kaur, Role of interleukin-6 and insulin resistance as screening markers for metabolic syndrome in patients of chronic obstructive pulmonary disease. A hospital-based cross-sectional study , Monaldi Archives for Chest Disease: Vol. 92 No. 3 (2022)
- Omid Rismantab, Seyed Aili Javad Moosavi, Mohammad Reza Farahnak, Maryam Dastoorpoor, Hanieh Raji, Role of CRP as a marker for discrimination of exudative and transudative pleural effusion , Monaldi Archives for Chest Disease: Vol. 92 No. 4 (2022)
- Mehul Agarwal, Madhur Joshi, Manohar Gupta, Neha Bharti, Amartya Chakraborti, Maldev Sonigra, Role of blood urea nitrogen and serum albumin ratio in predicting severity of community acquired pneumonia (CAP) , Monaldi Archives for Chest Disease: Vol. 92 No. 3 (2022)
- Josuel Ora, Emanuela Prendi, Maria Laura Attinà, Mario Cazzola, Luigino Calzetta, Paola Rogliani, Efficacy of respiratory tele-rehabilitation in COPD patients: Systematic review and meta-analysis , Monaldi Archives for Chest Disease: Vol. 92 No. 4 (2022)
- Ugo Corrà, Andrea Giordano, Marco Gnemmi, Fabiana Isabella Gambarin, Claudio Marcassa, Massimo Pistono, Cardiovascular disease patients and predictors of length of stay of residential of cardiac rehabilitation. A specific rehabilitation is mandatory in very old patients? , Monaldi Archives for Chest Disease: Vol. 92 No. 4 (2022)
- Andrea Segreti, Francesco Piccirillo, Simone Pasquale Crispino, Francesca Cocchia, Arianna Martucciello, Vito Calabrese, Fiorella Gurrieri, Francesco Grigioni, Simultaneous presence of Brugada and overgrowth syndromes , Monaldi Archives for Chest Disease: Vol. 94 No. 1 (2024)
You may also start an advanced similarity search for this article.
