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.
According to the researchers, “although this study alone does not provide sufficient evidence of clinical utility of sarilumab to treat COVID-19 [infection], data are consistent with a mortality benefit observed with IL-6R inhibitors in other large studies, when used in conjunction with corticosteroids [in] patients receiving [IMV].”
Disclosure: Some authors declared affiliations with pharmaceutical, biotech, and/or device companies. Please see the original reference for a full list of disclosures.
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