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A Randomized Placebo-Controlled Trial of Sarilumab in Hospitalized Patients with Covid-19
Sivapalasingam, Sumathi Lederer, David J. Bhore, Rafia Hajizadeh, Negin Criner, Gerard Hosain, Romana Mahmood, Adnan Giannelou, Angeliki Somersan-Karakaya, Selin O’Brien, Meagan
Sivapalasingam, Sumathi
Lederer, David J.
Bhore, Rafia
Hajizadeh, Negin
Criner, Gerard
Hosain, Romana
Mahmood, Adnan
Giannelou, Angeliki
Somersan-Karakaya, Selin
O’Brien, Meagan
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Pre-print
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2021-06-19
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Thoracic Medicine and Surgery
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https://doi.org/10.1101/2021.05.13.21256973
Abstract
BACKGROUND: Sarilumab (anti-interleukin-6 receptor-α monoclonal antibody) may attenuate the inflammatory response in Covid-19. METHODS: We performed an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial of intravenous sarilumab 200 mg or 400 mg in adults hospitalized with Covid-19. The phase 3 primary analysis population (cohort 1) was patients with critical Covid-19 receiving mechanical ventilation (MV) randomized to sarilumab 400 mg or placebo. The primary end point for phase 3 was the proportion of patients with ≥1-point improvement in clinical status from baseline to day 22. RESULTS: Four-hundred fifty-seven (457) and 1365 patients were randomized and treated in phases 2 and 3, respectively. Among phase 3 critical patients receiving MV (n=289; 34.3% on corticosteroids), the proportion with ≥1-point improvement in clinical status (alive not receiving MV) at day 22 was 43.2% in sarilumab 400 mg and 35.5% in placebo (risk difference [RD] +7.5%; 95% confidence interval [CI], –7.4 to 21.3; P=0.3261), representing a relative risk improvement of 21.7%. Day 29 all-cause mortality was 36.4% in sarilumab 400 mg versus 41.9% in placebo (RD –5.5%; 95% CI, –20.2 to 8.7; relative risk reduction 13.3%). In post hoc analyses pooling phase 2 and 3 critical patients receiving MV, the hazard ratio (HR) for death in sarilumab 400 mg compared with placebo was 0.76 (95% CI, 0.51 to 1.13) overall, improving to 0.49 (95% CI, 0.25 to 0.94) in patients receiving corticosteroids at baseline. CONCLUSION: In hospitalized patients with Covid-19 receiving MV, numerical benefits with sarilumab did not achieve statistical significance, but benefit may be greater in patients receiving corticosteroids. A larger study is required to confirm this observed numerical benefit.
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