Covid-19: Anti-inflammatory treatment baricitinib reduces deaths in patients admitted to hospital, finds trial

Anti-inflammatory treatment baricitinib, which is normally used to treat rheumatoid arthritis, reduces the risk of death in patients admitted to hospital with severe covid-19 by around one fifth, the Randomised Evaluation of Covid-19 Therapy (Recovery) trial has reported.1

Researchers leading the trial from the University of Oxford said that the benefit of baricitinib was on top of those seen for dexamethasone2 and tocilizumab,3 the two other anti-inflammatory treatments that the trial previously found to reduce the risk of death in these patients.

The trial’s joint chief investigator Martin Landray, professor of medicine and epidemiology at Oxford Population Health, said, “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.”

Speaking at a Science Media Centre briefing on 3 March, Landray added that “collectively these treatments are reducing the risk of death to these patients by well over a half, although the exact number will vary depending on the patient.” The team has estimated that a course of baricitinib treatment would cost around £250.

The results have so far only been released through a preprint, although the researchers have said they will be submitting to a peer reviewed journal shortly.

In the study, which ran from February to December 2021, 4148 patients were randomly allocated to receive usual care plus baricitinib (4 mg once daily for 10 days or until discharge from hospital, if sooner) and were compared with 4008 patients randomly allocated to receive usual care alone.

At randomisation, 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 were receiving oxygen and one quarter (27%) were receiving additional respiratory support.

Treatment with baricitinib was found to reduce deaths significantly, with 513 (12%) of the patients in the baricitinib group dying within 28 days compared with 546 (14%) in the usual care group, a reduction of 13% (age adjusted rate ratio 0.87, 95% confidence interval 0.77 to 0.98; P=0.026).

The researchers noted that “the size of benefit was somewhat smaller than that suggested by previous trials.” Other smaller studies had estimated that allocation to a Janus kinase (JAK) inhibitor such as baricitinib reduced 28 day mortality by about two fifths. Recovery alone reported this reduction as closer to one eighth, but when the research team combined all nine studies in an updated meta-analysis, they found that allocation to baricitinib or another JAK inhibitor was associated with a reduction in 28 day mortality of one fifth.

The trial also reported that patients receiving baricitinib were more likely to be discharged alive within 28 days (80% v 78%, age adjusted rate ratio 1.10, 95% CI 1.04 to 1.15; P<0.001). Baricitinib also reduced the chance of progressing to invasive mechanical ventilation or death from 17% to 16% (risk ratio 0.90, 95% CI 0.81 to 0.99, P=0.026).

The benefit of baricitinib remained regardless of which other covid-19 treatments (corticosteroids, tocilizumab, remdesivir) the patients were receiving, and whether they were vaccinated or not, the team said.

Joint chief investigator Peter Horby, professor of emerging infectious diseases at the University of Oxford, 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.”

Baricitinib was granted emergency use authorisation in the US in November 2020 and was recommended for use in combination with remdesivir. In February 2022, the US National Institutes of Health guidelines then advised it should be used for patients on dexamethasone who have rapidly increasing oxygen needs and systemic inflammation. In January 2022 the World Health Organisation gave a strong recommendation for the use of baricitinib in combination with corticosteroids in patients with severe or critical covid-19.