Tocilizumab may lower risk for COVID-19 progression, but not mortality

Tocilizumab may lower the odds of needing mechanical ventilation among patients hospitalized with COVID-19 pneumonia, but not the risk for death, according to research published in the New England Journal of Medicine.

“Tocilizumab, an anti–interleukin-6 receptor monoclonal antibody, has been approved for the treatment of multiple inflammatory diseases, and appeared to improve outcomes in patients with COVID-19 pneumonia in observational studies in the United States and globally,” Carlos Salama, MD, associate professor of medicine at Icahn School of Medicine and Mount Sinai Hospital, and colleagues wrote. “However, randomized trials of tocilizumab have shown mixed results in patients with varying degrees of COVID-19 disease severity as well as in populations with various background standards of care.”

Salama and colleagues conducted a phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of tocilizumab (Actemra, Genentech) in patients hospitalized with COVID-19 pneumonia who were not on mechanical ventilation.

The researchers enrolled patients from the United States, Mexico, Kenya, South Africa, Peru and Brazil. Study sites were selected based on their enrollment of high-risk or minority populations.

Participants were randomly assigned 2:1 to receive intravenous tocilizumab in addition to standard care or placebo with standard care. The researchers evaluated outcomes at day 28 and continued to follow patients until day 60.

A total of 389 patients were randomized, of whom 56% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native and 12.7% were white.

Among participants, 225 of those in the tocilizumab group and 115 in the placebo group completed the trial and were included in the analyses.

Salama and colleagues found that the cumulative percentage of participants who were placed on mechanical ventilation or died at day 28 was 12% (95% CI, 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3-27.4) in the placebo group (HR = 0.56; 95% CI, 0.33 to 0.97).

By day 28, death from any cause occurred in 10.4% of patients who received tocilizumab compared with 8.6% of patients who received placebo (weighted difference = 2 percentage points; 95% CI, –5.2 to 7.8).

According to Salama and colleagues, serious adverse events were observed in 15.2% of patients who were given tocilizumab and 19.7% of patients who were given placebo.

“Our trial showed that tocilizumab plus standard care was more efficacious than placebo plus standard care in reducing the likelihood of the composite outcome of progression to mechanical ventilation or death among hospitalized patients with COVID-19 pneumonia who were not receiving mechanical ventilation; however, there was no difference in the incidence of death from any cause,” Salama and colleagues wrote, adding that the reduced risk for mechanical ventilation was observed in patients who are typically underrepresented in clinical trials.