For patients hospitalized with severe COVID-19 Baricitinib (an anti-inflammatory drug) reduces mortality. Benefits found: - In addition to steroids (e.g. dexamethasone) - With or without tocilizumab - In a wide range of patients |
The Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial has shown that baricitinib, an anti-inflammatory drug typically used to treat rheumatoid arthritis, reduces the risk of death when given to hospitalized patients with severe COVID-19. The benefit was added to those of dexamethasone and tocilizumab, two other anti-inflammatory treatments that had previously been shown to reduce the risk of death in these patients.
The University of Oxford-led RECOVERY trial has been testing a range of potential treatments for patients admitted to hospital with COVID-19 since March 2020. Between February and December 2021, 4,008 patients randomized to care alone were compared with 4,148 patients who were randomly assigned to usual care plus baricitinib. The dose of baricitinib tablets was 4 mg once daily for 10 days (or until discharge from the hospital if earlier).
At the time of randomization, 95% of patients were receiving a corticosteroid such as dexamethasone, 23% were receiving tocilizumab, and 20% were receiving the antiviral drug remdesivir. Two-thirds (68%) of patients received oxygen and a quarter (27%) received additional respiratory support.
Treatment with baricitinib significantly reduced deaths: 513 (12%) of patients in the baricitinib group died within 28 days compared with 546 (14%) patients in the usual care group, a 13% reduction ( age-adjusted rate ratio 0.87, 95% Confidence Interval [CI] 0.77 to 0.98; p= 0.026).
The benefit of baricitinib was consistent regardless of what other COVID-19 treatments patients were also receiving, including corticosteroids, tocilizumab, or remdesivir.
Patients receiving baricitinib were also more likely to be discharged alive within 28 days (80% vs 78%, age-adjusted rate ratio 1.10, 95% CI 1.04-1.15 ; p<0.001).
Among patients who were not on invasive mechanical ventilation when they entered the trial, baricitinib reduced the chance of progressing to invasive mechanical ventilation or death from 17% to 16% (hazard ratio 0.90, [95% CI: 0.81 a 0.99], p = 0.026).
There was no evidence that the short course of baricitinib used in RECOVERY increased the risk of other infections or thrombosis (blood clotting complications).
RECOVERY significantly strengthens evidence from previous trials that baricitinib is beneficial in severe cases of COVID-19 and provides new evidence of the additional benefit of baricitinib on top of other immunomodulatory treatments. RECOVERY is twice as large as the eight previous trials of baricitinib and similar drugs (known as JAK inhibitors) for the combination treatment of COVID-19.
Overall, the nine trials, involving about 12,000 patients, found that use of baricitinib (or another JAK inhibitor) reduced deaths in patients hospitalized with COVID-19 by about a fifth (rate ratio 0.80 , 95% CI: 0.71 to 0.89, p < 0.001).
Sir Martin Landray, Professor of Medicine and Epidemiology at Oxford Population Health and joint principal investigator of RECOVERY, said: "It is now well established that in people admitted to hospital due to severe COVID-19, an overactive immune response is a driver. key to lung damage.
Today’s results not only show that baricitinib treatment improves the chances of survival for patients with severe COVID-19, but that this benefit is additional to other treatments that reduce the overactive immune response, such as dexamethasone and tocilizumab. "This opens up the possibility of using combinations of anti-inflammatory drugs to further reduce the risk of death for some of the sickest patients."
Sir Peter Horby, Professor of Emerging Infectious Diseases at the Nuffield Department of Medicine, University of Oxford, and Joint Chief Investigator of RECOVERY, said: "This result confirms and extends previous findings, providing greater certainty that baricitinib is beneficial and new data to guide treatment of COVID-19 patients with a combination of drugs to dampen the immune response As always, the next challenge is to ensure that this and other treatments for COVID-19 are available and affordable for everyone can benefit, regardless of where they live.”
Mark Rivvers (51), deputy porter at Fitzwilliam College, University of Cambridge, was involved in the baricitinib study in the RECOVERY trial when he was admitted to Addenbrooke’s Hospital with severe COVID-19 in September 2021. He said: "I was in hospital for almost a month, mostly in an intensive care unit. Everything in my body seemed to be fighting against everything else: I was on almost constant respiratory support, I developed sepsis and had pneumonia throughout my lungs. But I saw that it was my duty to participate in the RECOVERY trial, because I knew that no matter what happened to me, I was doing something positive to help others. I am very pleased with the result with baricitinib and I hope that it can now be used to benefit many others. I would like to thank the leaders of the RECOVERY trial, and also to all the staff at Addenbrooke’s Hospital,
Health and Social Care Secretary Sajid Javid said: “As we learn to live with COVID, it will be absolutely vital to have access to a growing number of safe and effective treatments for the virus, such as our revolutionary dexamethasone.”
’This is promising news from the government-funded RECOVERY trial and shows, once again, how the UK is leading the world in identifying life-saving treatments for NHS patients.
’Many thanks to all the researchers, doctors and volunteers involved in this work. “Our medical and scientific experts will now consider the results before making any decisions about next steps.”
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 monoclonal antibody combination (casirivimab plus imdevimab) targeting viral spike protein, known as Ronapreve (June 2021).
These discoveries have changed clinical practice around the world and are 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 everyone involved in the NIHR-supported RECOVERY trial has led to the discovery of another "life-saving treatment against COVID-19. We are particularly grateful to the 47,000 participants who have participated in the study so far, without whom these revolutionary discoveries would not be possible."
Professor Patrick Chinnery, clinical director at the Medical Research Council, said: "These new results from RECOVERY show that even more patient lives can be saved by targeting the immune system in a targeted way, adding to the benefits already shown. with dexamethasone.
A manuscript providing more details on these results has been submitted to medRxiv and will be submitted to a peer-reviewed medical journal shortly.
