Although treatment with sarilumab, an anti-interluekin 6 receptor (IL-6R) monoclonal antibody, was not associated with clinical improvement nor a decreased mortality risk in patients hospitalized with severe COVID-19 infection, it may be efficacious among those receiving corticosteroids. These findings were published in Clinical Infectious Diseases.

Researchers conducted an adaptive phase randomized, double-blind, placebo-controlled phase 2/3 study to determine the effect of sarilumab in adult patients hospitalized with severe and critical COVID-19 infection. Eligible patients were aged 18 years and older, had laboratory-confirmed SARS-CoV-2 infection, and were receiving supplemental oxygen. In phase 2, patients (N=457) were randomly assigned in a 2:2:1 fashion to receive either intravenous (IV) sarilumab 400 mg (n=180), IV sarilumab 200 mg (n=187), or placebo (n=90), with subsequent stratification by corticosteroid use and disease severity. The researchers considered patients receiving low-flow supplemental oxygen as severely ill. Patients who required either transfer to an intensive care unit or supplemental oxygen via nonrebreather mask, high-flow nasal cannula, and noninvasive or invasive mechanical ventilation (IMV) were considered critically ill. Phase 3 included patients (N=1365) with critical and severe COVID-19 infection who were randomly assigned to receive IV sarilumab at a dose of 400 mg (n=582,), 200 mg (n=489), or placebo (n=294). The primary endpoint of the phase 3 study was clinical improvement of 1-point or more on a 7-point scale between baseline and day 22, with a 1-point improvement indicating that IMV was no longer required.

Among patients included in phase 3, 750 (54.9%) were critically ill and 347 (25.4%) were severely ill. Of these patients, 21.8% were on IMV at baseline, 33.0% were not on IMV, and 0.3% were receiving extracorporeal membrane oxygenation. The median patient age was 61 years, 68% were men, the median duration of illness was 9 days, and 34.3% received systemic corticosteroids. Among patients in the 400-mg sarilumab and placebo groups who were on IMV at baseline, 43.2% and 35.5% had clinical improvement of 1-point or more at day 22 (risk difference [RD], 7.5%; 95% CI, -7.4 to 21.3; P =.3261), respectively. Of patients in the 400-mg sarilumab and placebo groups who were not on IMV at baseline, 57.4% and 64.8% had clinical improvement of 1-point or more at day 22 (RD, -7.5%; 95% CI, -18.3 to 3.9), respectively. Of note, sarilumab was not efficacious vs placebo among patients with severe illness and those with multisystem organ dysfunction.

Among patients in the 400-mg salirumab and placebo groups who were receiving IMV and corticosteroids at baseline (n=50), 44.0% and 68.2% died (hazard ratio [HR], 0.49; 95% CI, 0.25-0.94), respectively. Of patients who were receiving IMV without corticosteroids at baseline (n=129), 37.2% of those in the 400-mg sarilumab group and 39.7% of those in the placebo group died (HR, 0.92; 95% CI, 0.56-1.52).

This study was limited by heterogeneity among patients who were critically ill, potential underpowering due to the use phase 2 data to estimate the sample size of those included in phase 3, and that adequate dose response and multiple dosing were not evaluated.

Reference

Sivapalasingam S, J Lederer D, Bhore R, Hajizadeh N, Criner G et al. Efficacy and safety of sarilumab in hospitalized patients with COVID-19: a randomized clinical trial. Clin Infect Dis. Published online February 26, 2022. doi.10.1093/cid/ciac153

Safety, Efficacy of Sarilumab in Patients Hospitalized With Severe COVID-19

Reference

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