Arthritis drug may reduce mortality in hospitalized COVID-19 patients

Adding the rheumatoid arthritis drug baricitinib to another immune-modulating treatment reduces the risk of death in hospitalized patients with severe COVID-19, the results of a major study suggest.

Data from the “Randomized evaluation of COVID-19 therapy” (RECOVERY) trialwhich have not yet been peer-reviewed, have shown that adding the janus kinase (JAK) inhibitor baricitinib to usual care reduces the risk of progression to invasive mechanical ventilation or death of the patient by 17% to 16% (relative risk 0.90, [95% CI 0.81 to 0.99], P=0.026).

Patients who received baricitinib were also more likely than patients receiving usual care alone to be discharged within 28 days (80% versus 78%, age-adjusted rate ratio 1.10, 95% CI 1 .04-1.15; P

The University of Oxford-led study randomized 4,008 patients to usual care and 4,148 patients to usual care plus a dose of 4 mg baricitinib once daily for 10 days, or until discharge .

When randomized, usual care for 95% of all patients was on a corticosteroid such as dexamethasone; 23% were receiving the rheumatoid arthritis drug, tocilizumab, and 20% were receiving the antiviral, remdesivir.

More than two-thirds (68%) of patients were receiving oxygen and 27% were receiving respiratory support, such as noninvasive mechanical ventilation.

Martin Landray, Professor of Medicine and Epidemiology at Oxford Population Health and Joint Chief Investigator for RECOVERY, said: “It is now well established that in people admitted to hospital with severe COVID-19, an overactive immune response is a key driver of lung damage.

“Today [3 March 2022] the results show not only that treatment with baricitinib improves the chances of survival for patients with severe COVID-19, but that this benefit is in addition to that of other treatments that attenuate the overactive immune response, such as dexamethasone and tocilizumab.

“This opens up the possibility of using combinations of anti-inflammatories to further reduce the risk of death in some of the sickest patients.”

Overall, 513 (12%) patients in the baricitinib group died within 28 days compared to 546 (14%) patients in the usual care group, a reduction of 13% (rate ratio adjusted by age: 0.87, 95% confidence interval [CI] 0.77 to 0.98; p = 0.026).

The researchers concluded in the paper that the benefit of baricitinib was consistent regardless of other COVID-19 treatments patients were also receiving, including dexamethasone, tocilizumab or remdesivir.

They added that there was no evidence that the short course of baricitinib used in RECOVERY increased the risk of other infections or blood clotting.

Ahimalaipet Ramanan, honorary professor of pediatric rheumatology at the University of Bristol, said the RECOVERY results further confirm baricitinib’s role in reducing mortality in adults with COVID-19. “Although the RECOVERY trial is not a placebo-controlled trial, which is an important limitation, the important aspect of the finding of this article is that baricitinib is effective in reducing mortality, even in people treated with a blockade of IL-6 (eg, tocilizumab),” he said.

“As an oral agent with a short half-life and potentially cheaper, this makes baricitinib a more attractive agent after steroids in low/middle income countries. This article adds additional weight to the WHO guidelines recently published which state that the steroids, tocilizumab and baricitnib are the three drugs with strong evidence of use in COVID.

Baricitinib is the fourth treatment to be shown to be effective in the RECOVERY trial, after dexamethasone, tocilizumab and the monoclonal antibody cocktail Ronapreve (casirivimab plus imdevimab).