To the Editor:
We read with great interest the article by Price and colleagues1 in CHEST (October 2020) reporting tocilizumab use in coronavirus disease 2019 (COVID-19) patients with suspected cytokine release syndrome (CRS). Despite the large number of patients and the results reported, we would like to raise some concerns about their conclusions.
First, the definition of CRS in their study is unclear. A classification of CRS’ severity according to Lee and colleagues2 would have made it possible to classify subjects by severity more finely, thus identifying subgroups more likely to benefit from treatment. Indeed, the presence of other organ failure in patients was not detailed except for mechanical ventilation, suggesting low-grade CRS.
Second, two findings highlighted by the authors are the decrease in C-reactive protein (CRP) and the disappearance of fever, features also reported in another study of tocilizumab in COVID-19 by Hermine and colleagues.3 Tocilizumab use is associated with an expected decrease in CRP because of its pharmacological effect. Hence the biological results suggest only tocilizumab usage, and considering the decrease of CRP as efficiency in COVID-19 treatment could be an overstatement.
Third, supplementary material shows that the standard-of-care consisted of atazanavir and hydroxychloroquine, two off-label treatments for COVID-19, further reducing the external validity of the study. In addition, up to 38% of patients in the severe group received corticosteroids, a treatment now recommended by the World Health Organization for severe COVID-19.4 Overall, isolating the individual effect of tocilizumab among these therapies is difficult, particularly in an observational study, because we do not have the results of the control group.
These limitations call into question the authors’ conclusion that tocilizumab may reduce mortality in COVID-19, especially since the publication of randomized clinical trials with negative results on mortality (Hermine and colleagues3 and Stone and colleagues5). Further prospective studies are mandatory to define tocilizumab’s place in the therapeutic arsenal for COVID-19.
Footnotes
FINANCIAL/NONFINANCIAL DISCLOSURES: None declared.
References
- 1.Price C.C., Altice F.L., Shyr Y. Tocilizumab treatment for cytokine release syndrome in hospitalized patients with coronavirus disease 2019: survival and clinical outcomes. Chest. 2020;158(4):1397–1408. doi: 10.1016/j.chest.2020.06.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
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