Interleukin-6 Receptor Antagonists in Critically ill Patients with COVID-19

METHODS
We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial,
adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting
organ support in the intensive care unit (ICU), were randomly assigned to receive
tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard
care (control). The primary outcome was respiratory and cardiovascular organ support–
free days, on an ordinal scale combining in-hospital death (assigned a value
of −1) and days free of organ support to day 21. The trial uses a Bayesian statistical
model with predefined criteria for superiority, efficacy, equivalence, or futility. An
odds ratio greater than 1 represented improved survival, more organ support–free
days, or both.
RESULTS
Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that
time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to
control. The median number of organ support–free days was 10 (interquartile range,
−1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab
group, and 0 (interquartile range, −1 to 15) in the control group. The median
adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14)
for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as
compared with control, yielding posterior probabilities of superiority to control of
more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed
improved survival in the pooled interleukin-6 receptor antagonist groups, yielding
a hazard ratio for the comparison with the control group of 1.61 (95% credible
interval, 1.25 to 2.08) and a posterior probability of superiority of more than
99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor
antagonists.
CONCLUSIONS
In critically ill patients with Covid-19 receiving organ support in ICUs, treatment
with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved
outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.)