A comparison of the effectiveness of different doses of tocilizumab and sarilumab in the treatment of severe COVID-19: a natural experiment due to drug shortages

Maaike C. Swets*, Rob J. Moss, Flip Kor, Doranne Hilarius, Dirk Jan A.R. Moes, Willemijn EM Berkhout, Leon M. van den Toorn, Niels C.Gritters van den Oever, Renee de Valk, Frits R. Rosendaal, Nicole Hunfeld, Geert H. Groeneveld, Mark G.J. de Boer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
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Abstract

Objectives: Interleukin (IL)-6 inhibitors are administered to treat patients hospitalized with COVID-19. In 2021, due to shortages, different dosing regimens of tocilizumab, and a switch to sarilumab, were consecutively implemented. Using real-world data, we compare the effectiveness of these IL-6 inhibitors. Methods: Hospitalized patients with COVID-19, treated with IL-6 inhibitors, were included in this natural experiment study. Sixty-day survival, hospital- and intensive care unit (ICU) length of stay, and progression to ICU or death were compared between 8 mg/kg tocilizumab, fixed-dose tocilizumab, low-dose tocilizumab, and fixed-dose sarilumab treatment groups. Results: A total of 5485 patients from 49 hospitals were included. After correction for confounding, increased hazard ratios (HRs) for 60-day mortality were observed for fixed-dose tocilizumab (HR 1.20, 95% confidence interval [CI] 1.04-1.39), low-dose tocilizumab (HR 1.12, 95% CI 0.97-1.31), and sarilumab (HR 1.24, 95% CI 1.08-1.42), all relative to 8 mg/kg. The 8 mg/kg dosing regimen had lower odds of progression to ICU or death. Both hospital- and ICU length of stay were shorter for low-dose tocilizumab than for the 8 mg/kg group. Conclusion: We found differences in the probability of 60-day survival and the incidence of the combined outcome of mortality or ICU admission, mostly favoring 8 mg/kg tocilizumab. Because of potential time-associated residual confounding, further clinical studies are warranted.

Original languageEnglish
Pages (from-to)57-62
Number of pages6
JournalInternational Journal of Infectious Diseases
Volume129
DOIs
Publication statusPublished - Apr 2023

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Publisher Copyright: © 2023 The Author(s)

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