Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19
Results from the REMAP-CAP trial show in adults commencing organ support in ICU, tocilizumab (n=353) and sarilumab (n=48) improved days free of organ support (median 10 and 11 vs 0 with control [n=402]) and 90-day survival (pooled HR 1.61; 95% credible interval 1.25 to 2.08).
Source:
New England Journal of Medicine
SPS commentary:
A related editorial discusses the results of this study, and those of the COVACTA trial, with apparently contradictory results. Whilst REMAP-CAP found a single injection of tocilizumab or sarilumab reduced in-hospital mortality and increased organ support-free days, COVACTA found no difference between tocilizumab and placebo in mortality, and tocilizumab did not improve clinical status at day 28 (median of 1 [discharged or ready for discharge] for tocilizumab and 2 [out of intensive care and not receiving supplemental oxygen] for placebo).
The editorial discusses the differences among the trials, the greatest of which likely relates to the periods of time over which they were conducted. In COVACTA, only a minority were treated with glucocorticoids, which are now universally used in patients with severe disease, and use was higher in the placebo group (28.5% v 19.4% in the tocilizumab group). In contrast, use of glucocorticoids was high in the REMAP-CAP study, and also in the RECOVERY trial, the preliminary results of which also show a reduction in mortality with tocilizumab. Indeed, preliminary results of a subgroup analysis in the RECOVERY trial indicated those receiving glucocorticoids had a survival advantage, suggesting a treatment interaction with interleukin inhibition.
Another difference between the studies was the timing of initiation of anti-interleukin-6 therapy. It is possible that the value of this treatment is dependent on this timing, only being beneficial if proximate to an acute late inflammatory decompensation event. The article concludes that “we are left with evidence of benefit from interleukin-6 inhibitors, at least under some circumstances, but how to best use them remains unclear”.
An interim Clinical Commissioning Policy recommends that NHS trusts/ health boards consider prescribing a single dose of tocilizumab to eligible hospitalised patients with COVID-19 pneumonia, typically as adjuvant treatment to dexamethasone as standard of care, following the announcement of the findings of the RECOVERY trial. Sarilumab continues to be recommended for critically ill patients being treated with non-invasive ventilation or invasive mechanical ventilation, who have not already received tocilizumab.