Drug Shortage Helps Identify Optimal Tocilizumab Dosing for Severe COVID-19

Results of a study comparing different dosing regimens of interleukin-6 (IL-6) inhibitors suggest tocilizumab 8 mg/kg is associated with the lowest risk of mortality or intensive care unit (ICU) admission among adults hospitalized with COVID-19 infection. These study findings were published in the International Journal of Infectious Diseases.

Owing to drug shortages in 2021, researchers conducted a natural-experiment study to compare outcomes of different dosing regimens among adult patients hospitalized with COVID-19 receiving IL-6 inhibitors. Patients (N=5485) who received intravenous tocilizumab or sarilumab between March and December 2021 were included in the analysis. Patients were divided into 4 treatment groups on the basis of guideline recommendations at the time of hospitalization. The treatment options were as follows:

• tocilizumab 8 mg/kg (group 1; n=2212);
• fixed-dose (600 mg) tocilizumab (group 2; n=1196);
• low-dose (400 mg) tocilizumab (group 3; n=843); or
• sarilumab 400 mg (group 4; n=1234).

The primary outcome was survival time; secondary outcomes included survival time in the ICU, the occurrence of ICU admission or mortality, and the duration ICU and hospital admission. Differences in survival time and mortality risk were evaluated via multivariable Cox proportional hazards regression, with adjustments for age, sex, immunocompromised status, and Charlson comorbidity index score.

Among patients in all 4 groups, the majority were men (range, 62.0%-65.8%), most were aged 50 years and older, and 2.7% to 3.8% were immunocompromised. The overall rate of in-hospital mortality was 26.7%. Stratified by treatment group, the lowest rate of mortality was noted among patients in group 1 (22.9%), followed by those in groups 2 (25.9%), 3 (30.3%), and 4 (31.7%).

Treatment with tocilizumab 8 mg/kg was found to be associated with the greatest survival benefit. Compared with patients in group 1, the risk of 60-day mortality was highest among those in group 4 (hazard ratio [HR], 1.24; 95% CI, 1.08-1.42), followed those in groups 2 (HR, 1.20; 95% CI, 1.04-1.39) and 3 (HR, 1.12; 95% CI, 0.97-1.31).

Receipt of tocilizumab 8 mg/kg also was associated with the lowest risk of mortality in a subgroup analysis among only patients who required ICU admission. Compared with patients in group 1, the risk for progression to ICU admission or mortality was highest among patients in group 4 (HR, 1.43; 95% CI, 1.26-1.63), followed by those in group 3 (HR, 1.41; 95% CI, 1.22-1.63) and group 2 (HR, 1.24; 95% CI, 1.09-1.42).

Limitations of this study include the use of real-world data, potential confounding, and the lack of data on COVID-19 vaccination status.

“We found that in the complete hospital population, sarilumab, low dose tocilizumab and fixed dose tocilizumab led to worse survival compared to the 8 mg/kg group. The 8 mg/kg would therefore be the first-choice treatment option,” the researchers concluded. They added that using fixed-dose or low-dose tocilizumab in response to drug shortages, as a way to treat more patients, “should be considered with caution.”

This article originally appeared on Infectious Disease Advisor