Journal Information
Vol. 27. Issue 1.
Pages 86-87 (January - February 2021)
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Vol. 27. Issue 1.
Pages 86-87 (January - February 2021)
Letter to the Editor
DOI: 10.1016/j.pulmoe.2020.10.004
Open Access
Interleukin-6 blockade with tocilizumab in COVID-19: Does it live up to its hype?
C.S. Kowa,
Corresponding author

Corresponding author.
, S.S. Hasanb,c
a School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia
b Department of Pharmacy, University of Huddersfield, Huddersfield, United Kingdom
c School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, Australia
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A recent systematic review by Cortegiani et al.1 reviewed the evidence and appraised the quality of evidence concerning the use of tocilizumab in patients with coronavirus disease 2019 (COVID-19). Despite a thorough appraisal of a large number of clinical studies (n = 28) on tocilizumab in patients with COVID-19, Cortegiani et al.1 concluded that there is still insufficient evidence on its clinical efficacy in patients with COVID-19 because these studies are associated with a high risk of bias and poor quality. We would like to complement the discussion on the evidence of tocilizumab use in patients with COVID-19.

Interleukin (IL)-6 blocking agents such as tocilizumab have been touted as the potential treatment for COVID-19 since the recognition of the cytokine storm associated with a severe course of COVID-19, which involves increased levels of several cytokines where one of them is IL-6. However, a more pressing question is “Do increased concentrations of an IL-6 imply that its neutralisation will be effective in COVID-19?” While a recent observational study2, not included in the systematic review, demonstrated mortality benefits associated with the use of COVID-19, the two recent randomized controlled trials3,4 did not replicate the findings. The randomized, double-blinded, placebo-controlled COVACTA trial3 among hospitalized patients with COVID-19 reported no difference in 28-day mortality between the tocilizumab arm and placebo arm (19.7% and 19.4%, respectively). Furthermore, based on the results released on September 18, 2020, from the randomized, double-blind, placebo-controlled EMPACTA trial4, there was no statistical difference in 28-day mortality between patients who received tocilizumab and patients who received a placebo (10.4% and 8.6%, respectively).

The findings from randomized controlled trials have proved that the use of tocilizumab in COVID-19 did not live up to the hype, where the increased concentration of IL-6 does not imply that its neutralization will be effective in COVID-19. There is a possibility that the wrong cytokine was targeted to dampen the cytokine storm in COVID-19. A recent prospective study by Blot et al.5 compared the concentrations of IL-6 between 27 patients with COVID-19 pneumonia and 36 patients with non-COVID-19 pneumonia. It was reported that the plasma concentrations of IL-6 were significantly lower in the patients with COVID-19 pneumonia compared to the patients with pneumonia other than COVID-19 (121.0 pg/mL versus 460.4 pg/mL).

The findings of this prospective study, coupled with the findings from two randomized controlled trials that failed to detect mortality benefits with tocilizumab, suggest that IL-6 may not be the cytokine that drives the progression of COVID-19. The use of tocilizumab is not harmless since it may predispose patients to the development of secondary infections. We suggest a shift in focus and to target other mediators of hyperinflammatory state in patients with COVID-19.

Conflicts of interest

The authors have no conflicts of interest.

A. Cortegiani, M. Ippolito, M. Greco, V. Granone, A. Protti, C. Gregoretti, et al.
Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review.
N. Biran, A. Ip, J. Ahn, R.C. Go, S. Wang, S. Mathura, et al.
Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study.
Lancet Rheumatol, 2 (2020), pp. e603-12
I. Rosas, N. Bräu, M. Waters, R.C. Go, B.D. Hunter, S. Bhagani, et al.
Tocilizumab in hospitalized patients with COVID-19 pneumonia. Preprint.
medRxiv, (2020),
Roche. Roche’s phase III EMPACTA study showed Actemra/RoActemra reduced the likelihood of needing mechanical ventilation in hospitalised patients with COVID-19 associated pneumonia. [Accessed 24 September 2020].
M. Blot, A. Bourredjem, C. Binquet, L. Piroth, LYMPHONIE Study Group.
Is interleukin 6 the right target in COVID-19 severe pneumonia?.
Am J Respir Crit Care Med, (2020),
Copyright © 2020. Sociedade Portuguesa de Pneumologia

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