Actemra Reduces Deaths, Mechanical Ventilation for COVID-19 in Early Data
Early results from the University of Oxford’s RECOVERY trial showed Roche’s immunosuppressant Actemra reduced deaths and the need for mechanical ventilation in severe COVID patients. Genentech’s Actemra is approved to treat rheumatoid arthritis and cytokine release syndrome resulting from chimeric antigen receptor-T cell therapy. The data was posted online before peer-reviewed publication in the preprint archive medRxiv.
According to the findings, about half of the 4,116 adults in the trial added Actemra to the standard of care while the other half received the standard of care alone. Mortality improved from 33% in the 2,094 patients who did not receive Actemra to 39% in the 2,022 patients who did. Mortality dropped from 22% to 19% in patients that did not require a ventilator, and from 48% to 47% in patients who required mechanical ventilation.
The largest benefits were seen in patients receiving corticosteroids as part of the standard of care. Across both groups, 82% of enrolled patients received a corticosteroid, primarily dexamethasone. The mortality rate of patients who received a corticosteroid was 33%, which dropped to 27% for patients who added Actemra. In patients who did not receive a corticosteroid, Actemra increased mortality from 35% to 39%.
The study’s findings help detail a confusing picture based on earlier results. In January, results from a small study in Brazil suggested Actemra did not help patients with severe COVID-19. But larger, earlier trials suggested that Actemra decreased mortality and shortened recovery times in intensive care. In a Roche-sponsored study last September, Actemra decreased by 44% the likelihood patients would progress to mechanical ventilation or death compared to those receiving placebo plus standard of care.
Martin Landray, an author on the paper and a professor of medicine and epidemiology at the University of Oxford, previously said he expected the results of this trial to help make “definitive decisions about exactly what the role of this drug is.” Earlier data from the RECOVERY trial last June showed dexamethasone alone decreased mortality among patients receiving either invasive mechanical ventilation or oxygen. That data contributed to the inclusion of dexamethasone in recommendations from the National Institutes of Health as part of the standard of care treatment for COVID-19 patients requiring oxygen.
In the new preprint, the authors recommended updating clinical guidelines for COVID-19 patients with hypoxia and evidence of systematic inflammation. The data suggests treatment with a combination of a systemic corticosteroid and Actemra could reduce mortality by a third for patients on oxygen, and nearly a half for patients on more invasive mechanical ventilation, and the effects are additive, they said.
The authors also combined data from this trial with seven smaller, earlier ones that tested Actemra. Those trials did not show significant mortality benefit on their own, but “when all 8 trials are considered together, allocation to [Actemra] is associated with a 13% proportional reduction in 28-day mortality.”