Tocilizumab in addition to standard of care in the management of COVID-19: a meta-analysis of RCTs

Main Article Content

victor Mutua https://orcid.org/0000-0001-5748-8332
Brandon Michael Henry
Chris von Csefalvay
Isaac Cheruiyot https://orcid.org/0000-0002-1211-8247
Jens Vikse
Giuseppe Lippi
Brian Bundi https://orcid.org/0000-0003-1170-2641
Newnex Mong'are https://orcid.org/0000-0003-4526-4096

Keywords

Covid-19, SARS-COV-2, Tocilizumab, IL-6 inhibitor, Mortality

Abstract

Objective: We performed a systematic review and meta-analysis for exploring clinical benefits and safety of tocilizumab in addition to standard of care (SOC) in treating patients with coronavirus disease 2019 (COVID-19).


Methods: An electronic search was carried out in PubMed, EMBASE, Cochrane Library, and Science Direct, as well as in medRxiv preprint server, to identify eligible studies. Only randomized Controlled Trials (RCTs) that compared mortality events and/or adverse events between a tocilizumab + SOC group and a SOC-only control group were included. The primary outcome was 28-day mortality. Secondary outcomes include progression to severe disease, defined as need for mechanical ventilation (MV) or intensive care unit (ICU) admission, and adverse events (AE).


Results: A total of nine studies (6,490 participants) could be included in this meta-analysis, with 3,358 participants in the tocilizumab + SOC group and 3,132 participants in the SOC-only group. The overall mortality rate was lower in the tocilizumab group compared to the SOC-only group, though the difference was not statistically significant (odds ratio [OR], 0.87; 95% CI, 0.73-1.04; I2, 15%). This finding was unaffected by subgroup analyses based on initial use of steroids or mechanical ventilation at baseline. Patients receiving tocilizumab were 26% less likely to progress to MV, and this difference was statistically significant (OR, 0.74; 95% CI, 0.64-0.86; I2, 0%). Among patients who were not in ICU at randomization, the tocilizumab group had 34 % lower rate of ICU admission compared to the SOC-only group (OR, 0.66; 95% CI, 0.40-2.14; I2, 29%). The occurrence of serious infections was lower in the tocilizumab group (OR, 0.57; 95% CI, 0.36-0.89; I2, 21%).


Conclusion: Tocilizumab is generally well-tolerated in COVID-19. Although this drug does not appear to have a significant benefits on survival, it may have a role in preventing progression to intensive care and MV.

Downloads

Download data is not yet available.
Abstract 72 |

References

1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020;395(10223):497–506.
2. Surveillances V. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19)—China, 2020. China CDC Wkly. 2020;2(8):113–22.
3. Lippi G, Plebani M. Cytokine “storm”, cytokine “breeze”, or both in COVID-19? Clin Chem Lab Med CCLM. 2021;59(4):637–9.
4. Aziz M, Haghbin H, Abu Sitta E, Nawras Y, Fatima R, Sharma S, et al. Efficacy of tocilizumab in COVID‐19: a systematic review and meta‐analysis. J Med Virol. 2021;93(3):1620–30.
5. Lan S-H, Lai C-C, Huang H-T, Chang S-P, Lu L-C, Hsueh P-R. Tocilizumab for severe COVID-19: a systematic review and meta-analysis. Int J Antimicrob Agents. 2020;56(3):106103.
6. Lin W-T, Hung S-H, Lai C-C, Wang C-Y, Chen C-H. The effect of tocilizumab on COVID-19 patient mortality: A systematic review and meta-analysis of randomized controlled trials. Int Immunopharmacol. 2021;107602.
7. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009 Aug 18;151(4):264–9, W64.
8. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.
9. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Bmj. 2003;327(7414):557–60.
10. Gordon AC, Mouncey PR, Al-Beidh F, Rowan KM, Nichol AD, Arabi YM, et al. Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N Engl J Med. 2021;
11. Horby PW, Pessoa-Amorim G, Peto L, Brightling CE, Sarkar R, Thomas K, et al. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial. Medrxiv. 2021;
12. Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med. 2021;384(16):1503–16.
13. Veiga VC, Prats JA, Farias DL, Rosa RG, Dourado LK, Zampieri FG, 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.
14. Hermine O, Mariette X, Tharaux P-L, Resche-Rigon M, Porcher R, Ravaud P, 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(1):32–40.
15. Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, et al. Tocilizumab in patients hospitalized with Covid-19 pneumonia. N Engl J Med. 2021;384(1):20–30.
16. Salvarani C, Dolci G, Massari M, Merlo DF, Cavuto S, Savoldi L, 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(1):24–31.
17. Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS, et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med. 2020;383(24):2333–44.
18. Soin AS, Kumar K, Choudhary NS, Sharma P, Mehta Y, Kataria S, 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;
19. Tleyjeh IM, Kashour Z, Damlaj M, Riaz M, Tlayjeh H, Altannir M, et al. Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis. Clin Microbiol Infect. 2020;
20. Kow CS, Hasan SS. The effect of tocilizumab on mortality in hospitalized patients with COVID-19: a meta-analysis of randomized controlled trials. Eur J Clin Pharmacol. 2021;1–6.
21. Kotak S, Khatri M, Malik M, Malik M, Hassan W, Amjad A, et al. Use of tocilizumab in COVID-19: a systematic review and meta-analysis of current evidence. Cureus. 2020;12(10).
22. Zhao M, Lu J, Tang Y, Dai Y, Zhou J, Wu Y. Tocilizumab for treating COVID-19: a systemic review and meta-analysis of retrospective studies. Eur J Clin Pharmacol. 2020;1–9.
23. Cavalcanti AB, Zampieri FG, Rosa RG, Azevedo LC, Veiga VC, Avezum A, et al. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19. N Engl J Med. 2020;383(21):2041–52.
24. Furtado RH, Berwanger O, Fonseca HA, Corrêa TD, Ferraz LR, Lapa MG, et al. Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial. The Lancet. 2020;396(10256):959–67.
25. Horby PW, Roddick A, Spata E, Staplin N, Emberson JR, Pessoa-Amorim G, et al. Azithromycin in hospitalised patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. medRxiv. 2020;
26. Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020;27(6):992-1000. e3.
27. Henry BM, Benoit SW, Vikse J, Berger BA, Pulvino C, Hoehn J, et al. The anti-inflammatory cytokine response characterized by elevated interleukin-10 is a stronger predictor of severe disease and poor outcomes than the pro-inflammatory cytokine response in coronavirus disease 2019 (COVID-19). Clin Chem Lab Med CCLM. 2021;59(3):599–607.
28. Lippi G, Sanchis-Gomar F, Favaloro EJ, Lavie CJ, Henry BM. Coronavirus disease 2019–associated coagulopathy. In: Mayo Clinic Proceedings. Elsevier; 2021. p. 203.

Most read articles by the same author(s)

1 2 3 > >>