Current best evidence for clinical care (more info)
BACKGROUND: Coronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti-interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear.
METHODS: We randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28.
RESULTS: A total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P = 0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, -?5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group.
CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.).
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This is a really important question. Tocilizumab use has been widespread for COVID under the assumption that improved IL-6 levels must be better for patients. This well designed study helps answer that question.
Well done study assessing the use of an IL6 inhibitor in mild-to-moderate Covid disease that reveals a benefit in a combined primary outcome of mechanical ventilation and death.
Based on hyperinflammation in Covid-19, this RCT assessed efficacy and safety of the anti–IL6 receptor antibody tocilizumab in hospital-admitted COVID-19 pneumonia patients not requiring ventilatory support. The population was enriched for highest risk patients from racial and ethnic minority populations (56% Hispanic/Latino, 15% Black, 13% American / Alaskan Native). In patients already treated with steroids (80-90%) and anti-virals (80%), addition of 1 or 2 doses of IV tocilizumab (8 mg/kg) over 8-24hrs reduced risk of mechanical ventilation or death (hazard ratio 0.56; 95% CI, 0.33 - 0.97). Death was not statistically different between treatment groups, and there were no evidence of any increase in serious adverse events with tocilizumab.