IL-6 Receptor Antagonists Improved Outcomes in Critically Ill COVID-19 Patients

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Investigators assessed how critically ill adult patients with COVID-19 and respiratory or cardiovascular organ support responded to tocilizumab or sarilumab treatments.

Critically ill COVID-19 patients receiving organ support benefited from therapy sarilumab or tocilizumab, which are interleukin (IL)-6 receptor antagonists, according to the results of a study published in The New England Journal of Medicine.

The Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community Acquired Pneumonia (REMAP-CAP; NCT02735707) trial investigators recruited critically ill adult patients (N=865) with COVID-19 who were being treated in intensive care units (ICU) with respiratory or cardiovascular organ support. Patients were randomly selected to receive tocilizumab (8 mg/kg of body weight infusion once or twice daily; n=366), sarilumab (400 mg infusion once daily; n=48), standard care (n=412), or another intervention (n=69). Clinical outcomes were assessed.

The mean patient age was 61.4 years (SD, 12.7), 73% were men, 72% were White, and median BMI was 30.5 kg/m2 (interquartile range [IQR], 26.8-34.9).

The median number of days free from organ support was 10 (IQR, -1 to 16), 11 (IQR, 0-16), and 0 (IQR, -1 to15) for the tocilizumab, sarilumab, and control cohorts, respectively. Compared with controls, the adjusted odds ratio (aOR) of organ support-free days was 1.64 (95% credible interval [CrI], 1.25-2.14) for tocilizumab recipients and 1.76 (95% CrI, 1.17-2.91) for sarilumab recipients. These values corresponded with superiority over control of 99.9% for tocilizumab and 99.5% for sarilumab.

In-hospital mortality was 27% (n=108) in the pooled IL-6 receptor antagonist groups, compared with 36% (n=142) in the control group. Survival was associated with both tocilizumab (aOR, 1.64; 95% CrI, 1.14-2.35) and sarilumab (aOR, 2.01; 95% CrI, 1.18-4.71), corresponding with 99.6% and 99.5% superiority over control, respectively.

The treatment groups were associated with discharge from ICU (tocilizumab: hazard ratio [HR], 1.42; 95% CrI, 1.18-1.70; sarilumab: HR, 1.64; 95% CI, 1.21%-2.45%) and discharge from hospital (tocilizumab: HR, 1.41; 95% CrI, 1.18-1.70; sarilumab: HR, 1.51; 95% CI, 1.17%-2.40%).

Investigators did not observe any serious adverse events among sarilumab recipients. There were a total of 9 adverse events reported in the tocilizumab group (bleeding events [n=5], cardiac events [n=2], bacterial infection [n=1], deterioration of vision [n=1]) and 11 adverse events reported in the control group (thromboses [n=7], bleeding events [n=4]).

This study may have been limited by its short duration. At the time data publication, some patients remained hospitalized. It is unclear what the long-term outcomes of either treatment will be.

These data indicated that treating patients with IL-6 receptor antagonist therapies decreased the days they were on organ support and mortality rates, and increased likelihood of discharge from ICU and hospital among those who were critically with a SARS-CoV-2 infection.

Disclosure: Several study authors declared affiliations with industry. Please refer to the original article for a full list of authors’ disclosures.


Gordon AC, Mouncey PR, Al-Beidh F, et al; The REMAP-CAP Investigators. Interleukin-6 receptor antagonists in critically ill patients with covid-19. N Engl J Med. Published online February 25, 2021. doi:10.1056/NEJMoa2100433