A Randomized Placebo-Controlled Trial of Sarilumab in Hospitalized Patients with Covid-19

Sivapalasingam, S.; Lederer, D.; Bhore, R.; Hajizadeh, N.; Criner, G.; Hossain, R.; Mahmood, A.; Giannelou, A.; Somersan-Karakaya, S.; O'Brien, M.; Boyapati, A.; Parrino, J.; Musser, B.; Labriola-Tompkins, E.; Ramesh, D.; Purcell, L.; Gulabani, D.; Kampman, W.; Waldron, A.; Ng Gong, M.; Saggar, S.; Sperber, S.; Menon, V.; Stein, D.; Sobieszczyk, M.; Park, W.; Aberg, J.; Brown, S.; Kosmicki, J.; Horowitz, J.; Ferreira, M.; Baras, A.; Kowal, B.; DiCioccio, A. T.; Akinlade, B.; Nivens, M.; Braunstein, N.; Herman, G.; Yancopoulos, G.; Weinreich, D.; Team, Sarilumab-COVID-19 Study

BACKGROUND Sarilumab (anti-interleukin-6 receptor-alpha; 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.