Safety and Efficacy of Tocilizumab 4 or 8 mg/kg in Hospitalized Patients With Moderate to Severe COVID-19 Pneumonia: A Randomized Clinical Trial

Abstract

Background

Tocilizumab, an interleukin 6 receptor (IL-6R) antagonist monoclonal antibody, has shown efficacy in patients with COVID-19 pneumonia, but the optimal dose is unknown.

Methods

Patients hospitalized for moderate-to-severe COVID-19 pneumonia were randomized 1:1 to receive standard care treatment and 1 to 2 doses of intravenous tocilizumab 4 or 8 mg/kg (open-label). Primary pharmacokinetic and pharmacodynamic end points were serum concentrations of tocilizumab and soluble IL-6R (sIL-6R), IL-6, ferritin, and C-reactive protein (CRP), from baseline to day 60. The secondary end point was safety. Key exploratory efficacy end points included clinical status, time to discharge, mortality rate, and incidence of mechanical ventilation.

Results

Of 100 patients randomized, 49 received tocilizumab 4 mg/kg and 48 received 8 mg/kg. In pharmacokinetic and sIL-6R assessments, dose-dependent differences were seen in patients who received 1 or 2 doses of 4 or 8 mg/kg. Serum concentrations of IL-6, ferritin, and CRP and safety outcomes were comparable between groups. Through day 60, serious adverse events were reported in 30.6% and 25.0% of patients in the 4- and 8-mg/kg group, respectively. Eight patients (16.3%) in the 4-mg/kg group and 6 (12.5%) in the 8-mg/kg group died. Exploratory time-to-event outcomes favored 8-mg/kg within the first 2 weeks.

Conclusions

In patients with moderate-to-severe COVID-19 pneumonia who received tocilizumab 4 or 8 mg/kg, pharmacokinetic and sIL-6R assessments showed expected dose-dependent effects; pharmacodynamic assessments and safety were comparable, with no new safety signals. Further study is required before a lower dose of tocilizumab can be recommended in patients with COVID pneumonia.