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

• Published in: International journal of infectious diseases 2023-04, Vol.129, p.57-62
• Main Authors: Swets, Maaike C., Moss, Rob J., Kor, Flip, Hilarius, Doranne, Moes, Dirk Jan A.R., Berkhout, Willemijn EM, van den Toorn, Leon M., van den Oever, Niels C. Gritters, de Valk, Renee, Rosendaal, Frits R., Hunfeld, Nicole, Groeneveld, Geert H., de Boer, Mark G.J.
• Format: Article
• Language: English
• Subjects: COVID-19; COVID-19 Drug Treatment; Humans; IL-6 inhibitor; Sarilumab; SARS-CoV-2; Tocilizumab; Treatment Outcome
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2023.01.041

•Interleukin-6 inhibitors are used to treat patients hospitalized with COVID-19.•Due to drug shortages, different dosing regimens were used.•60-day mortality was the lowest for patients treated with 8 mg/kg tocilizumab.•The 8 mg/kg dosing regimen had the lowest odds of progression to the intensive care unit or death. 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.