Hospitalized COVID-19 patients who received the monoclonal anti-inflammatory antibody tocilizumab were less likely to die or require invasive mechanical ventilation, according to preliminary results from the UK RECOVERY study published today on the medRxiv prepress server.
Led by researchers at the University of Oxford, the ongoing study of the Randomized Assessment of COVID-19 Therapy (RECOVERY) involved assigning 4,116 severely ill coronavirus patients to receive intravenous tocilizumab, a rheumatoid arthritis drug or usual treatment. The majority (82%) of the participants also received a systemic corticosteroid, such as dexamethasone.
Greater chances of leaving the hospital alive
Of the 2,022 patients who received tocilizumab from April 23, 2020 to January 25, 2021, 596 (29%) died within 28 days of hospitalization, against 694 of 2,094 (33%) of patients who received usual care (reason for fees [RR], 0.86), for an absolute difference of 4%. The drug also increased the chances of discharge from the hospital with life in 28 days from 47% to 54% (RR, 1.22).
Patients in the tocilizumab group who did not receive invasive mechanical ventilation when included in the study were also less likely to progress to the need for this treatment (from 38% to 33%; RR, 0.85), and less started to need dialysis (5 % vs 7%).
But the drug did not affect rates of successful weaning from mechanical ventilation or the subsequent need for non-invasive or invasive respiratory support among those who did not need such support at the start of the study. The authors said the benefits of tocilizumab seemed particularly apparent to those who also received a systemic corticosteroid, but added that it may have been due to chance.
All subgroups of patients saw benefits, including those who needed supplemental oxygen with a face mask and those who needed mechanical ventilation in an intensive care unit. The average age of the participants was 63.6 years.
Among the 4,116 participants, 562 (14%) received invasive mechanical ventilation, 1,686 (41%) received non-invasive respiratory support and 1,868 (45%) did not receive respiratory support, except for supplemental oxygen. All patients had low oxygen levels and signs of inflammation.
Three serious adverse effects have been attributed to tocilizumab, including ear infection, Staphylococcus aureus bloodstream infection and lung abscess. All conditions were resolved after treatment.
One third to half less deaths
RECOVERY researchers have been testing different possible treatments for coronavirus since March 2020, with tocilizumab added to the study in April. Recently, on February 3, the US National Institutes of Health said data to recommend for or against the use of tocilizumab in patients requiring invasive or non-invasive mechanical ventilation or oxygen is insufficient, but the researchers said their findings require an update to those guidelines, as well as actions to increase the global availability and accessibility of tocilizumab.
“Our data suggest that in patients with COVID-19 who are hypoxic and have evidence of systematic inflammation, treatment with a combination of systemic corticosteroids plus tocilizumab should reduce mortality by about a third for patients receiving simple oxygen and almost one-half for those receiving invasive mechanical ventilation, “wrote the researchers.
The authors noted that seven previous randomized studies of tocilizumab in patients with COVID-19 produced mixed results that, taken together, did not suggest a significant reduction in mortality rates.
They said, however, that the RECOVERY study has more than three times as many deaths to study as in previous combined studies. Thus, they added, all eight studies together showed that the drug is associated with a 13% drop in mortality within 28 days (RR, 0.87).
The lead author, Peter Horby, PhD, at the University of Oxford, called the findings of the benefits of tocilizumab plus dexamethasone “impressive and most welcome” in an article on the RECOVERY website. “Previous tests with tocilizumab showed mixed results and it was not clear which patients could benefit from the treatment,” he said. “We now know that the benefits of tocilizumab extend to all COVID patients with low oxygen levels and significant inflammation.”
The authors state that the results will be submitted to a peer-reviewed medical journal.