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Another Drug Shows Mortality Benefit for Severe COVID-19

— Pragmatic RECOVERY trial validates drug with prior "mixed results"

MedpageToday
A box of Actemra (tocilizumab) for infusion over a computer rendering of a COVID-19 virus surrounded by antibodies.

Tocilizumab (Actemra) showed a slight but statistically significant mortality benefit in critically ill COVID-19 patients, according to a from the U.K.'s pragmatic RECOVERY trial.

Of patients treated with tocilizumab, an IL-6 inhibitor used for rheumatoid arthritis and related conditions, 29% died within 28 days versus 33% of patients treated with usual care (rate ratio 0.86, 95% CI 0.77-0.96, P=0.007), researchers stated. This amounted to a number needed to treat of 25 to save one additional life.

And tocilizumab improved the probability of "discharge alive" after 28 days, from 47% to 54% (RR 1.23, 95% CI 1.12-1.34, P<0.0001) among hospitalized patients of varying severity, from those needing supplemental oxygen to those requiring intubation.

RECOVERY co-chief investigator Peter Horby, MD, PhD, of the University of Oxford, noted that previous trials showed "mixed results" and it was "unclear which patients might benefit from the treatment."

"The results from the RECOVERY trial clearly show the benefits of tocilizumab and dexamethasone in tackling the worst consequences of COVID-19 -- improving survival, shortening hospital stay, and reducing the need for mechanical ventilators," said co-investigator Martin Landray, PhD, of the University of Oxford, in the group's statement.

Ryan Zarychanski, MD, of University of Manitoba, that "in addition to anticoagulation, I suspect this will become new standard as data emerges. This drug isn't quite as inexpensive as steroids or heparin."

Current NIH guidelines state there is to recommend for or against use of tocilizumab for severe COVID-19 patients, and recommend against its use for patients not requiring ICU level care.

For patients not requiring mechanical ventilation at the start of the trial, a significantly smaller percentage of patients treated with tocilizumab progressed to mechanical ventilation or death versus those receiving usual care (38% and 33%, respectively; RR 0.85, 95% CI 0.78-0.93, P=0.0005). However, there was no evidence the drug improved patients' chances of stopping mechanical ventilation.

(RECOVERY) trial is a pragmatic trial notable for finding a mortality benefit with the inexpensive steroid dexamethasone, as well as a lack of mortality benefit for the recently FDA-approved remdesivir, though its findings have been disputed by other trials.

Tocilizumab was added to the RECOVERY trial in April 2020 for patients requiring oxygen who had evidence of inflammation, with enrollment stopped in January 2021 due to sufficient evidence to establish meaningful benefit or not.

Overall, 2,022 patients were randomized to receive tocilizumab and 2,094 to usual care. Notably, 82% of patients in both groups were treated with a systemic steroid, such as dexamethasone.

These results have yet to be published in a peer-reviewed journal, or even as a preprint, though the authors promised they would be available via medRxiv shortly.

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    Molly Walker is deputy managing editor and covers infectious diseases for ľֱ. She is a 2020 J2 Achievement Award winner for her COVID-19 coverage.