U.K.’s RECOVERY trial finds baricitinib cut risk of death when added to usual care

Adding the Janus kinase (JAK) inhibitor baricitinib (Olumiant) to usual care was shown to significantly reduce COVID deaths in hospitalized patients, the U.K.’s RECOVERY trial found.

The drug, which is normally used to treat rheumatoid arthritis, was associated with a 13% lower 28-day mortality rate compared to usual care alone (age-adjusted rate ratio [RR] 0.87, 95% CI 0.77-0.98, P=0.026).

Baricitinib was also linked with a higher rate of being discharged alive within 28 days (80% vs 78%, age-adjusted RR 1.10, 95% CI 1.04-1.15, P<0.01), and a lower risk of progressing to invasive mechanical ventilation or death among patients who were not initially on mechanical ventilation (RR 0.90, 95% CI 0.89-0.99, P=0.026).

In a press release, the RECOVERY investigators noted that over all of the nine trials, comprising about 12,000 patients, use of baricitinib or another JAK inhibitor was associated with a one-fifth reduction in death among patients hospitalized with COVID (RR 0.80, 95% CI 0.71-0.89, P<0.01).

This is now the fourth treatment to show a mortality benefit in the pragmatic RECOVERY trial, following dexamethasone, IL-6 blocker tocilizumab and the monoclonal antibody combination of casirivimab plus imdevimab.

The FDA authorized baricitinib, co-administered with remdesivir (Veklury), for severe COVID patients in November 2020.

“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,” said Martin Landray, PhD, of Oxford Population Health, in a statement.

“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,” added Landray, who is also joint chief investigator on the RECOVERY trial.

This phase of the RECOVERY trial randomized 4,008 hospitalized COVID patients to usual care and 4,148 to usual care plus a 4 mg tablet of baricitinib daily for 10 days or until discharge from the hospital. Nearly all (95%) of patients received a corticosteroid, like dexamethasone, while a little less than a quarter received tocilizumab (Actemra) and 20% received remdesivir. A little under 70% were receiving oxygen, while 27% received additional respiratory support.

Overall, 12% of patients receiving baricitinib died versus 14% of those receiving usual care alone. This was consistent, regardless if patients were on corticosteroids, tocilizumab, or remdesivir.

They also noted that a short course of baricitinib did not raise the risk of thrombosis or infections.

These results have been submitted to the pre-print server medRxiv for publication and will soon be submitted to a peer-reviewed journal.