A Randomized Placebo-Controlled Trial of Sarilumab in Hospitalized Patients with Covid-19
Lederer, David J.
Purcell, Lisa A.
Ng Gong, Michelle
Sperber, Steven J.
Stein, David K.
Sobieszczyk, Magdalena E.
Aberg, Judith A.
Brown, Samuel M.
Kosmicki, Jack A.
Horowitz, Julie E.
Ferreira, Manuel A.
DiCioccio, A. Thomas
Nivens, Michael C.
Yancopoulos, George D.
Weinreich, David M.
GroupSarilumab-COVID-19 Study Team
DepartmentThoracic Medicine and Surgery
Permanent link to this recordhttp://hdl.handle.net/20.500.12613/7017
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AbstractBACKGROUND: 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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