Interleukin-6 Antagonists Show Clear Benefits for Those with Severe or Critical COVID-19

In a meta-analysis of randomized trials, use of IL-6 antagonists in certain hospitalized patients reduced mortality.

Randomized trials of IL-6 antagonists in patients hospitalized with COVID-19 have yielded conflicting results, although recent studies such as RECOVERY (NEJM JW Infect Dis Jun 2021and Lancet 2021 May 1; 397:1637) and REMAP-CAP (NEJM JW Infect Dis Apr 2021 and N Engl J Med 2021 Feb 25; [e-pub]) support the use of these agents in patients with severe or critical COVID-19. Now, the WHO has published a meta-analysis encompassing 10,930 hospitalized patients in 27 randomized trials of tocilizumab or sarilumab compared with usual care or placebo.

Participants who received an IL-6 antagonist had lower risk for death than those who received usual care or placebo (odds ratio, 0.86). The benefit of IL-6 blockade was evident only in participants also receiving corticosteroids. The decrease in mortality with IL-6 antagonists was seen in participants who required supplemental oxygen, high-flow nasal oxygen, or noninvasive ventilation, but not in those requiring mechanical ventilation or ECMO at randomization. The benefit was clearer for tocilizumab than for sarilumab (perhaps because a greater proportion were receiving concomitant corticosteroids and a lower fraction were mechanically ventilated in the former group). Secondary infections occurred in 21.9% of those who received an IL-6 antagonist and in 17.6% of those who received usual care or placebo.

Comment

Based on this study, the WHO updated its treatment guidelines to recommend co-administration of IL-6 antagonists with corticosteroids in patients hospitalized with severe or critical COVID-19. These recommendations are largely in agreement with those from the NIH and the Infectious Diseases Society of America. Whether using an IL-6 antagonist is better than a Jak inhibitor (which benefits a similar patient population) remains to be determined. What's clear, however, is the need to expand global access to IL-6 antagonists or Jak inhibitors to use together with corticosteroids in select patients hospitalized with COVID-19.

Reviewing Author

Rajesh T. Gandhi, MD

Disclosures

Grant/Research SupportNIH

Editorial BoardsUpToDate; ID Images (idimages.org); Infectious Diseases Society of America COVID-19 Treatment Guidelines; International Antiviral Society–USA (Guidelines Committee)

Leadership Positions in Professional SocietiesHIV Medicine Association; Infectious Diseases Society of America (Board of Directors)