The RECOVERY Trial, the world’s largest randomised trial of potential COVID-19 treatments, has found another drug that reduces the risk of death in hospitalised patients with the disease.
The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial showed that baricitinib, an anti-inflammatory drug normally used to treat rheumatoid arthritis, reduces the risk of death when given to hospitalised patients with severe COVID-19.
The benefit was in addition to those of dexamethasone and tocilizumab, two other anti-inflammatory treatments which have previously been shown to reduce the risk of death in these patients.
The trial, led by University of Oxford scientists and supported by the NIHR Oxford Biomedical Research Centre (BRC), has been testing a range of potential treatments for patients admitted to hospital for COVID-19 since March 2020.
Between February and December 2021, 4,008 patients randomly allocated to usual care alone were compared with 4,148 patients who were randomly allocated to usual care plus baricitinib. The dose of baricitinib tablets was 4mg once daily for 10 days (or until discharge from hospital if sooner). At randomisation, 95% of patients were receiving a corticosteroid such as dexamethasone, 23% were receiving tocilizumab, and 20% were receiving the anti-viral drug remdesivir. Two-thirds (68%) of patients were receiving oxygen and one quarter (27%) were receiving additional respiratory support.
Treatment with baricitinib significantly reduced deaths: 513 (12%) of the patients in the baricitinib group died within 28 days compared with 546 (14%) patients in the usual care group, a reduction of 13%. The benefit of baricitinib was consistent, regardless of which other COVID-19 treatments the patients were also receiving, including corticosteroids, tocilizumab, or remdesivir.
Patients receiving baricitinib were also more likely to be discharged alive within 28 days. Among patients not on invasive mechanical ventilation when entered into the trial, baricitinib reduced the chance of progressing to invasive mechanical ventilation or death from 17% to 16%.
RECOVERY considerably strengthens the evidence from earlier trials that baricitinib is beneficial in severe COVID-19, and provides new evidence of the additional benefit of baricitinib on top of other immunomodulatory treatments.
Sir Martin Landray, Professor of Medicine and Epidemiology at Oxford Population Health, and Joint Chief Investigator for RECOVERY, said: “It is now well-established that in people admitted to hospital because of severe COVID-19, an over-active immune response is a key driver of lung damage.
“Today’s results not only show that treatment with baricitinib improves the chances of survival for patients with severe COVID-19, but that this benefit is additional to that from other treatments that dampen down the over-active immune response, such as dexamethasone and tocilizumab. This opens up the possibility of using combinations of anti-inflammatory drugs to further drive down the risk of death for some of the sickest patients,” said Prof Landray, the Oxford BRC’s Theme Lead for Clinical Informatics and Big Data.
Sir Peter Horby, Professor of Emerging Infectious Diseases in the Nuffield Department of Medicine, University of Oxford, and Joint Chief Investigator for RECOVERY, said: “This result confirms and extends earlier findings, providing greater certainty that baricitinib is beneficial and new data to guide the treatment of COVID-19 patients with a combination of drugs to dampen the immune response. As always, the next challenge is ensuring this and other COVID-19 treatments are available and affordable for everyone who can benefit, regardless of where they live.”.
Baricitnib is the fourth treatment that the RECOVERY trial has shown to save lives, following the steroid dexamethasone (June 2020), the arthritis treatment tocilizumab (February 2021), and a combination of monoclonal antibodies (casirivimab plus imdevimab) targeting the viral spike protein, known as Ronapreve (June 2021). These discoveries have changed clinical practice worldwide and been credited with saving hundreds of thousands, if not millions, of lives.
Professor Nick Lemoine, Medical Director of the National Institute for Health Research (NIHR) Clinical Research Network, said: “The incredible contribution of all those involved in the NIHR-supported RECOVERY trial has led to the discovery of a further life-saving treatment against COVID-19. We’re particularly grateful to the 47,000 participants who have taken part in the study so far – without whom these game-changing discoveries would not be possible.”