Severe COVID-19 is characterised by lung damage, which can be associated with high concentrations of cytokines. Baricitinib, already available for the treatment of rheumatoid arthritis and moderate to severe eczema, is a JAK inhibitor that modulates the production of cytokines involved in inflammation. It was therefore investigated by the Oxford University-based RECOVERY trial as a possible treatment for COVID-19.
Following positive results from the RECOVERY trial, baricitinib is now recommended as an additional treatment option for patients admitted to hospital to manage the symptoms of COVID-19 pneumonia in the UK. The recommendation is outside of the current marketing authorisation and is based on data from the RECOVERY trial.
It is the third treatment from the trial to be made available on the NHS, following dexamethasone and tocilizumab. A fourth treatment, a combination of monoclonal antibodies casirivimab and imdevimab (Ronapreve) was approved but was withdrwan due to its ineffectiveness against the dominant Omicron variant.
Sir Martin Landray, professor of medicine and epidemiology at the University of Oxford, and joint chief investigator for the RECOVERY trial, said: ‘Baricitinib works in addition to other proven therapies (such as dexamethasone). Although we have effective vaccines and treatments, hospitalisation with COVID-19 is still associated with poor outcomes so it’s vital that we continue to use randomised trials to identify new therapies that can reduce risk further.'
Significant reduction in deaths
In the RECOVERY trial, baricitinib reduced 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 treatments which have previously been shown to reduce the risk of death in these patients.
Between February and December 2021, 8156 patients hospitalised with COVID-19 were randomised to receive usual care plus baricitinib tablets (4mg once daily for 10 days, or until discharge if sooner) or usual care alone. The patients also received dexamethasone, tocilizumab or remdesivir. Around two thirds of patients were receiving oxygen and around a quarter were receiving additional respiratory support.
Results showed a significant reduction in deaths. Among those patients treated with baricitinib, 12% of the patients died within 28 days compared to 14% of patients in the usual care group, a reduction of 13% (age-adjusted rate ratio 0.87 [95% CI 0.77–0.98, p=0.026). The benefit of baricitinib was consistent regardless of which other COVID-19 treatments the patients were also receiving.
The proportion of patients discharged alive by day 28 was also greater for the baricitinib arm (80% vs 78%). Among patients not on invasive mechanical ventilation at baseline, baricitinib reduced the chance of progressing to invasive mechanical ventilation or death from 17% to 16%.
NHS Medical Director Professor Steve Powis said: 'The more effective Covid treatments within the NHS arsenal, the more options doctors have to help patients who become seriously ill with Covid, preventing hospital admissions and saving lives.'
'Finding ways to beat Covid has showcased the very best of the NHS’s power to find creative and innovative ways to care for patients and implement new treatments, which includes in this case successfully repurposing an existing drug to treat a deadly virus,' he concluded.
Health and Social Care Secretary Sajid Javid said: 'It is fantastic that NHS patients are now able to access this highly effective treatment for COVID. Our world-leading national effort to identify new drugs to treat this virus continues as we add this game-changing medicine, baricitinib, to our arsenal.'
'As we live with the virus, having access to a growing number of treatments – alongside our lifesaving vaccination programme – is absolutely vital,' he added.