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

• DOI: 10.1016/j.ijid.2023.01.041
• Publication Date: 2023-02-02T19:07:51Z
• Authors: Maaike C. Swets; Rob J. Moss; Flip Kor; Doranne Hilarius; Dirk Jan A.R. Moes; Willemijn EM Berk...; Leon M. van den T...; Niels C. Gritters...; Renee de Valk; Frits R. Rosendaal; Nicole Hunfeld; Geert H. Groeneveld; Mark G.J. de Boer
• Keywords: SARS-CoV-2; IL-6 inhibitor; Sarilumab; COVID-19; Infectious and parasitic diseases; RC109-216; Tocilizumab; Article; 3. Good health; COVID-19 Drug Treatment; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; SDG 3 - Good Health and Well-being; Humans

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.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.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.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.