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

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.(<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</jats:ext-link> number, <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04315298">NCT04315298</jats:ext-link>).

Medienart:

Preprint

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

bioRxiv.org - (2021) vom: 30. Okt. Zur Gesamtaufnahme - year:2021

Sprache:

Englisch

Beteiligte Personen:

Sivapalasingam, Sumathi [VerfasserIn]
Lederer, David J. [VerfasserIn]
Bhore, Rafia [VerfasserIn]
Hajizadeh, Negin [VerfasserIn]
Criner, Gerard [VerfasserIn]
Hosain, Romana [VerfasserIn]
Mahmood, Adnan [VerfasserIn]
Giannelou, Angeliki [VerfasserIn]
Somersan-Karakaya, Selin [VerfasserIn]
O’Brien, Meagan [VerfasserIn]
Boyapati, Anita [VerfasserIn]
Parrino, Janie [VerfasserIn]
Musser, Bret [VerfasserIn]
Labriola-Tompkins, Emily [VerfasserIn]
Ramesh, Divya [VerfasserIn]
Purcell, Lisa A. [VerfasserIn]
Gulabani, Daya [VerfasserIn]
Kampman, Wendy [VerfasserIn]
Waldron, Alpana [VerfasserIn]
Gong, Michelle Ng [VerfasserIn]
Saggar, Suraj [VerfasserIn]
Sperber, Steven J. [VerfasserIn]
Menon, Vidya [VerfasserIn]
Stein, David K. [VerfasserIn]
Sobieszczyk, Magdalena E. [VerfasserIn]
Park, William [VerfasserIn]
Aberg, Judith A. [VerfasserIn]
Brown, Samuel M. [VerfasserIn]
Kosmicki, Jack A. [VerfasserIn]
Horowitz, Julie E. [VerfasserIn]
Ferreira, Manuel A. [VerfasserIn]
Baras, Aris [VerfasserIn]
Kowal, Bari [VerfasserIn]
DiCioccio, A. Thomas [VerfasserIn]
Akinlade, Bolanle [VerfasserIn]
Nivens, Michael C. [VerfasserIn]
Braunstein, Ned [VerfasserIn]
Herman, Gary [VerfasserIn]
Yancopoulos, George D. [VerfasserIn]
Weinreich, David M. [VerfasserIn]

Links:

Volltext [kostenfrei]

doi:

10.1101/2021.05.13.21256973

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XBI020560206