Early use of corticosteroids and sarilumab in SARS-Cov-2 pneumonia.

Abstract

The cytokine storm underlying the inflammatory phase of COVID19 has been suggested since the beginning of the pandemic as a target for treatment of the disease. The identification of the presence of elevated IL6 levels in patients with severe SARS-CoV-2 infection led to the hypothesis that the use of already marketed drugs whose mechanism of action is the inhibition of IL6 could result in clinical benefit for these patients. We hypothesised that the use of glucocorticoid-associated sarilumab in early stages of the proinflammatory phase of COVID19 could prevent progression to respiratory distress syndrome and death. Hospitalised patients with SARS-CoV2 pneumonia, treated with nasal cannula and with analytical parameters of inflammation, were randomised (1:1 ratio) to receive sarilumab + standard therapy (sarilumab group) or standard therapy (control group). In all cases, standard therapy included glucocorticoid treatment for at least 3 days at a dose equivalent to methylprednisolone mg/kg/day. The primary endpoint was the percentage of patients who progressed to severe respiratory failure (defined as a BRESCIA-COVID score ≥3), intensive care unit (ICU) admission or death at any time up to day 15. A total of 201 patients were included, of whom 99 were randomised to the sarilumab group and 102 to the control group. The percentage of patients who progressed to severe respiratory failure (BRESCIA≥3), ICU admission or death at any time up to day 15 was 16.6% in the sarilumab group and 15.69% in the control group (RR 1.03; 95% CI, 0.48 to 2.20). No differences in the safety profile between the two groups were detected. Mortality at day 28 was 2.02% in the sarilumab group vs. 1.96% in the control group (RR 1.03; 95% CI 0.14 - 7.46). In conclusion, an early intervention with sarilumab and glucocorticoids did not demonstrate clinical benefit in our study population compared to standard therapy.