Second JAK inhibitor has mortality advantage in severe COVID cases

Adding the Janus kinase (JAK) inhibitor baricitinib (Olumiant) to usual care has been shown to significantly reduce COVID deaths in hospitalized patients, according to the UK RECOVERY trial.

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 associated with a higher rate of live discharge within 28 days (80% versus 78%, age-adjusted RR 1.10, 95% CI 1.04-1.15, PP=0.026).

In a press release, RECOVERY researchers noted that across nine trials, including approximately 12,000 patients, use of baricitinib or another JAK inhibitor was associated with a one-fifth reduction in deaths in patients hospitalized with COVID (RR 0.80, 95% CI 0.71-0.89, P

It is now the fourth treatment to show a benefit in terms of mortality in the pragmatic RECOVERY trial, after dexamethasone, tocilizumab, another JAK inhibitor, and the monoclonal antibody combination casirivimab plus imdevimab.

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

“It is now well established that in people admitted to hospital with severe COVID-19, an overactive immune response is a key factor in lung damage,” said Martin Landray, PhD, of Oxford Population Health. , in a press release.

“This opens up the possibility of using combinations of anti-inflammatories to further reduce the risk of death in some of the sickest patients,” added Landray, who is also co-chief investigator of 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 one baricitinib 4 mg tablet daily for 10 days or until hospital discharge. Almost all (95%) of patients received a corticosteroid, such as dexamethasone, while just under a quarter received tocilizumab (Actemra) and 20% received remdesivir. Just under 70% received oxygen, while 27% received additional respiratory support.

Overall, 12% of patients receiving baricitinib died compared with 14% of those receiving usual care alone. This was consistent whether patients were taking corticosteroids, tocilizumab, or remdesivir.

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

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

  • Molly Walker is associate editor and covers infectious diseases for MedPage Today. She is the winner of the J2 Achievement Award 2020 for her COVID-19 coverage. To follow

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