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Drugs for COVID-19: tocilizumab

Published studies into the effects of tocilizumab in the treatment of patients with COVID-19 differ greatly in the way they have been designed and conducted. Comparisons are hampered by differences in aspects like the severity of the COVID pneumonia and the concomitant use of other anti-inflammatory and immunosuppressive drugs like corticosteroids. Two large randomised studies found a significant reduction of mortality after 28 days among patients treated with tocilizumab compared to those given a placebo. A recent Cochrane systematic review and meta-analysis confirmed this result and found a number-needed-to-treat of 31. Based on this, the preliminary advice is to give COVID patients with respiratory failure and deteriorating pneumonia a single dose of tocilizumab, in combination with dexamethasone, within 24 hours after the start of oxygen therapy with more than 6 L of oxygen a minute.

What is Ge-Bu’s opinion?
  • A systematic review and meta-analysis of eight randomised studies into tocilizumab showed a small but significant reduction of mortality on day 28 in patients with moderate or severe COVID-19 (NNT: 31).
  • For the time being, tocilizumab can be used, in combination with dexamethasone, for moderately or severely ill COVID patients within 24 hours after respiratory deterioration.
  • Questions remain about the category of patients who would benefit most from treatment with tocilizumab, the possible use of biomarkers to identify this category, the optimum timing of administration and the precise mechanism of action of this drug.

This article refers as much as possible to the current situation regarding drugs for COVID-19 and has been updated until just before publication. Studies and reports published after 5 June 2021 could not, however, be reviewed here.

  1. European Centre for Disease Prevention and Control. COVID-19 situation update worldwide. Available from: Accessed 3 juni 2021.
  2. van Stiphout F, Krens LL, Butalovic-Calasan M, Bosch TM. Geneesmiddelen bij COVID-19. Gebu. 2020;54(6-7):67-78.
  3. Kaye AG, Siegel R. The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review. PeerJ. 2020 Nov 2;8:e10322. doi: 10.7717/peerj.10322.
  4. 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. 2021 Mar;77(3):311-319. doi: 10.1007/s00228-020-03017-5. 
  5. Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS, et al. BACC Bay Tocilizumab Trial Investigators. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. N Engl J Med. 2020 Dec 10;383(24):2333-2344. doi: 10.1056/NEJMoa2028836. 
  6. Hermine O, Mariette X, Tharaux PL, Resche-Rigon M, Porcher R, Ravaud P; CORIMUNO-19 Collaborative Group. 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 Jan 1;181(1):32-40. doi: 10.1001/jamainternmed.2020.6820. Erratum in: JAMA Intern Med. 2021 Jan 1;181(1):144.
  7. Salvarani C, Dolci G, Massari M, Merlo DF, Cavuto S, Savoldi L, et al. RCT-TCZ-COVID-19 Study Group. Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial. JAMA Intern Med. 2021 Jan 1;181(1):24-31. doi: 10.1001/jamainternmed.2020.6615. 
  8. 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 Jan 7;384(1):20-30. doi: 10.1056/NEJMoa2030340. 
  9. Veiga VC, Prats JAGG, Farias DLC, Rosa RG, Dourado LK, Zampieri FG, et al. Coalition covid-19 Brazil VI Investigators. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. BMJ. 2021 Jan 20;372:n84. doi: 10.1136/bmj.n84. 
  10. 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 Apr 22;384(16):1503-1516. doi: 10.1056/NEJMoa2028700. 
  11. REMAP-CAP Investigators, 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 Apr 22;384(16):1491-1502. doi: 10.1056/NEJMoa2100433. 
  12. RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021 May 1;397(10285):1637-1645. doi: 10.1016/S0140-6736(21)00676-0.
  13. Ghosn L, Chaimani A, Evrenoglou T, Davidson M, Graña C, Schmucker C, et al. Interleukin-6 blocking agents for treating COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 Mar 18;3:CD013881. doi: 10.1002/14651858.CD013881.
  14. Furlow B. COVACTA trial raises questions about tocilizumab's benefit in COVID-19. Lancet Rheumatol. 2020 Oct;2(10):e592. doi: 10.1016/S2665-9913(20)30313-1.
  15. Mahase E. Covid-19: Arthritis drug trial for severe illness is stopped early after increase in deaths. BMJ. 2021 Jan 20;372:n186. doi: 10.1136/bmj.n186.
  16. McCreary EK, Meyer NJ. Covid-19 controversies: the tocilizumab chapter. BMJ. 2021 Jan 27;372:n244. doi: 10.1136/bmj.n244.
  17. Campochiaro C, Dagna L. The conundrum of interleukin-6 blockade in COVID-19. Lancet Rheumatol. 2020 Oct;2(10):e579-e580. doi: 10.1016/S2665-9913(20)30287-3. 
  18. Dodd LE, Freidlin B, Korn EL. Platform Trials - Beware the Noncomparable Control Group. N Engl J Med. 2021 Apr 22;384(16):1572-1573. doi: 10.1056/NEJMc2102446. 
  19. ECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. 
  20. College ter Beoordeling van Geneesmiddelen. CBG-MEB Geneesmiddeleninformatiebank. Samenvatting van de productkenmerken. Available from: 
  21. Leisman DE, Ronner L, Pinotti R, Taylor MD, Sinha P, Calfee CS, et al. Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes. Lancet Respir Med. 2020 Dec;8(12):1233-1244. doi: 10.1016/S2213-2600(20)30404-5. 
  22. Chen LYC, Hoiland RL, Stukas S, Wellington CL, Sekhon MS. Confronting the controversy: interleukin-6 and the COVID-19 cytokine storm syndrome. Eur Respir J. 2020 Oct 1;56(4):2003006. doi: 10.1183/13993003.03006-2020. 
  23. Fajgenbaum DC, Wu D, Goodman A, Wong R, Chadburn A, Nasta S, et al. Castleman Disease Collaborative Network Scientific Advisory Board diagnostic criteria international working group and treatment guidelines international working group. Insufficient evidence exists to use histopathologic subtype to guide treatment of idiopathic multicentric Castleman disease. Am J Hematol. 2020 Dec;95(12):1553-1561. doi: 10.1002/ajh.25992. 
  24. Stichting Werkgroep Antibioticabeleid. Medicamenteuze behandeling voor patiënten met COVID-19 (infectie met SARS-CoV-2). IL-6-remmers. Versie 9 maart 2021. Available from:
  25. National Institutes of Health. The COVID-19 treatment guidelines panel’s statement on the use of tocilizumab (and other interleukin-6-inhibitors) for the treatment of COVID-19. Versie 21 april 2021. Available from:
  26. Infectious Diseases Society of America. Guidelines on the treatment and management of patients with COVID-19. Tocilizumab. Versie 14 april 2021. Available from:
  27. National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. Versie 6 maart 2021. Available from:
  28. WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020 Aug;20(8):e192-e197. doi: 10.1016/S1473-3099(20)30483-7. Erratum in: Lancet Infect Dis. 2020 Oct;20(10):e250. 

*The literature refers to the Dutch text.


  • Erik P. Schwarz
  • Lisanne L. Krens, dr, pharmacist
  • Maja Bulatović-Ćalasan