january 2021 • medRxiv

Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19 – Preliminary report

The REMAP-CAP investigators

DOI: 10.1101/2021.01.07.21249390

Content curated by:David Rodrigues

Key message

Em pacientes gravemente doentes com Covid-19 admitidos em UCI a recever suporte respiratório ou cardiovascular, o tratamento com antagonistas do receptor de IL-6, tocilizumab e sarilumab associa-se a melhores resultados, incluindo menor mortalidade.

Analysis

Population

Doentes com COVID-19 admitidos em UCI por disfunção de orgão a receber suporte respiratório ou cardiovascular.

Method

Ensaio clinico aleatorizado (parte do ensaio REMAP) que testa a utilização de antagonistas IL-6 nas primeiras 24h de entrada na UCI. Doentes aleatorizados para receber tocilizumab (8 mg / kg) ou sarilumab (400 mg) ou tratamento padrão (controlo). O outcome primário foi uma escala ordinal que combina mortalidade hospitalar ( -1) e dias sem suporte de órgãos até o dia 21.

Results

Tocilizumab e sarilumab atingiram os pontos predefinidos para eficácia. 353 pacientes foram atribuídos ao tocilizumab, 48 ao sarilumab e 402 ao controlo. A mediana de dias sem suporte de órgão foi de 10 (intervalo interquartil [IQR] -1,16), 11 (IQR 0, 16) e 0 (IQR -1,15) para tocilizumab, sarilumab e controlo, respectivamente. A mortalidade hospitalar foi de 28,0% (98/350) para tocilizumab, 22,2% (10/45) para sarilumab e 35,8% (142/397) para o controlo. NNT =13

Abstract

Background The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. Methods We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours of commencing organ support in an intensive care unit, were randomized to receive either tocilizumab (8mg/kg) or sarilumab (400mg) or standard care (control). The primary outcome was an ordinal scale combining in-hospital mortality (assigned −1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with pre-defined triggers to declare superiority, efficacy, equivalence or futility. Results Tocilizumab and sarilumab both met the pre-defined triggers for efficacy. At the time of full analysis 353 patients had been assigned to tocilizumab, 48 to sarilumab and 402 to control. Median organ support-free days were 10 (interquartile range [IQR] −1, 16), 11 (IQR 0, 16) and 0 (IQR −1, 15) for tocilizumab, sarilumab and control, respectively. Relative to control, median adjusted odds ratios were 1.64 (95% credible intervals [CrI] 1.25, 2.14) for tocilizumab and 1.76 (95%CrI 1.17, 2.91) for sarilumab, yielding >99.9% and 99.5% posterior probabilities of superiority compared with control. Hospital mortality was 28.0% (98/350) for tocilizumab, 22.2% (10/45) for sarilumab and 35.8% (142/397) for control. All secondary outcomes and analyses supported efficacy of these IL-6 receptor antagonists. Conclusions In critically ill patients with Covid-19 receiving organ support in intensive care, treatment with the IL-6 receptor antagonists, tocilizumab and sarilumab, improved outcome, including survival. (ClinicalTrials.gov number: NCT02735707)