Tocilizumab for hospitalized patients with COVID-19
===================================================

* Kevin Afra
* Luke Y.C. Chen
* David Sweet

## Tocilizumab is an immunomodulatory drug that blocks the activity of interleukin-6 (IL-6)

Many patients with severe coronavirus disease 2019 (COVID-19) have immune misfiring characterized by a defective interferon response followed by elevated inflammatory cytokines, notably IL-6.1 Tocilizumab is a monoclonal IL-6 receptor antibody that is approved for use in inflammatory conditions.2

## Tocilizumab reduces mortality in patients with severe-tocritical COVID-19

Two large randomized controlled trials evaluating tocilizumab in patients with COVID-19 in hospital have been conducted. The Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) involving patients who were critically ill found that tocilizumab was superior to standard of care for 21-day mortality and organ support–free days.3 In-hospital mortality was 28.0% in the tocilizumab group versus 35.8% in the standard-of-care group (number needed to treat [NNT] = 12). The preprint publication of the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial showed that tocilizumab improved 28-day mortality: 29.5% of patients in the tocilizumab group died versus 33.1% in the standard-of-care group (NNT = 27).4 This benefit is additive to the benefit of corticosteroids.

## Hospitalized patients with COVID-19 who are not critically ill also benefit from tocilizumab

Patients in the RECOVERY trial were eligible for treatment with tocilizumab if they had hypoxia (oxygen saturation < 92% on room air or requiring supplemental oxygen) and systemic inflammation (C-reactive protein ≥ 75 mg/L). Benefits of tocilizumab appeared consistent in this trial across all levels of initial respiratory support.4

## Tocilizumab should be given early to eligible patients

Patients who are eligible for tocilizumab should not have treatment delayed. Both RECOVERY and REMAP-CAP, the only trials to show mortality benefit, administered tocilizumab in the early stages of hospital admission (median 1–2 d).3,4

## Tocilizumab appears to be safe for the treatment of COVID-19

Hypersensitivity, cytopenias, hepatic injury and gastrointestinal perforation are notable adverse effects of tocilizumab but have been uncommon in COVID-19 trials. However, patients with an aminotransferase level 5 times the upper limit of normal or a platelet count of less than 50 × 109/L were excluded from the REMAP-CAP trial.3

## Acknowledgement

The authors would like to acknowledge the dedication and hard work of the B.C. COVID-19 Therapeutics Committee throughout this pandemic.

## Footnotes

*   **Competing interests:** Kevin Afra and Luke Chen are members, and David Sweet is chair, of the B.C. COVID-19 Therapeutics Committee, which provides guidance on the most current research on use of therapies in management of COVID-19. Luke Chen has received support from GlaxoSmithKline for an ad board for mepolizumab. No other competing interests were declared.

*   This article has been peer reviewed.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: [https://creativecommons.org/licenses/by-nc-nd/4.0/](https://creativecommons.org/licenses/by-nc-nd/4.0/)

## References

1.  Chen LYC, Hoiland RL, Stukas S, et al. Confronting the controversy: interleukin-6 and the COVID-19 cytokine storm syndrome. Eur Respir J 2020;56:2003006.
    
    

2.  Product monograph: PrActemra (tocilizumab). Mississauga (ON): Hoffmann-La Roche; 2010 Apr. 30, revised 2021 Jan. 4. Available: [https://pdf.hres.ca/dpd_pm/00059560.PDF](https://pdf.hres.ca/dpd_pm/00059560.PDF) (2021 Feb. 12).
    
    

3.  1.  Gordon AC, 
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    REMAP-CAP Investigators, 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 Feb. 25 [Epub ahead of print]. doi: 10.1056/NEJMoa2100433.
    
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4.  1.  Horby PW, 
    2.  Pessoa-Amorim G, 
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    RECOVERY Collaborative Group; Horby PW, Pessoa-Amorim G, Peto L, et al. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial [preprint]. medRxiv 2021 Feb. 11. doi: 10.1101/2021.02.11.21249258.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1101/2021.02.11.21249258&link_type=DOI)