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15-07-2021 | Rheumatology | News | Article

Meta-analysis supports COVID-19 mortality benefit with IL-6 inhibitors

Claire Barnard

medwireNews: Treatment with interleukin (IL)-6 receptor antagonists is associated with a reduction in 28-day mortality risk among hospitalized patients with COVID-19, suggest findings from a meta-analysis published in JAMA.

The World Health Organization REACT working group analyzed data from 10,930 patients who participated in one of 27 randomized controlled trials comparing tocilizumab (n=19 trials), sarilumab (n=9), or siltuximab (n=1) with placebo or usual care.

Manu Shankar-Hari (Guy’s and St Thomas’ NHS Foundation Trust London, UK) and colleagues report that 21.8% of 6449 patients treated with an IL-6 inhibitor died during 28 days of follow-up, compared with 25.8% of the 4481 participants in the control group. In a fixed-effects meta-analysis, these results translated into a summary odds ratio (OR) of 0.86 significantly favoring IL-6 inhibitor use.

When participants were categorized according to corticosteroid use, this risk reduction was only seen among patients receiving concomitant corticosteroids (OR=0.78), but not in those receiving an IL-6 inhibitor without corticosteroids.

Subgroup analyses also demonstrated that the association between IL-6 inhibitor treatment and reduced mortality risk was “more marked” among participants who did not require invasive mechanical ventilation at baseline, as well as among patients treated with tocilizumab rather than sarilumab. The researchers note, however, that “comparisons between tocilizumab and sarilumab were indirect,” and “trials of sarilumab were generally done earlier in the pandemic than those of tocilizumab and before corticosteroids became the standard of care.”

Commenting on these findings in an accompanying editorial, Michael Matthay and Anne Luetkemeyer, both from the University of California, San Francisco in the USA, ask “how should IL-6 [receptor antagonists] best be used to benefit patients hospitalized for COVID-19?”

They say that the agents “should be reserved for patients who already have started taking glucocorticoids,” and suggest that “IL-6 [receptor antagonists] for critically ill patients may be most effective when given early in the disease course, whereas benefit may be unlikely when patients have received ventilatory support for several days or more.”

The editorialists note that “appropriate use of IL-6 inhibition in patients with low oxygen requirements is not clear.”

They conclude that these drugs “hold promise for patients hospitalized for COVID-19 with progressive disease and substantial oxygen requirements but are not yet merited for widespread use among patients with mild disease nor with prolonged invasive mechanical ventilation.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

15 July 2021: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.

JAMA 2021; doi:10.1001/jama.2021.11330
JAMA 2021; doi:10.1001/jama.2021.11121

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