Benefits of Adding Baricitinib to Usual Care in Hospitalized Patients with COVID-19

In the RECOVERY trial, adding baricitinib to dexamethasone reduced mortality.

The Janus kinase (JAK) inhibitor baricitinib reduces inflammation, a hallmark of severe COVID-19. Clinical trials have found that adding baricitinib to dexamethasone improves clinical outcomes in people hospitalized with COVID-19. Now, the results of the RECOVERY trial confirm this drug's beneficial role.

Between February and December 2021, 8156 patients hospitalized in the U.K. with COVID-19 were randomly assigned to receive usual care alone or usual care plus open-label baricitinib (4 mg daily for 10 days or until discharge). At randomization, about 95% of participants received dexamethasone and required respiratory support (oxygen, noninvasive ventilation, or mechanical ventilation). Mortality at day 28 was lower in the baricitinib group than in the usual group (12% vs. 14%; age-adjusted rate ratio, 0.87). Rates of non–SARS-CoV-2 infection, thrombosis, or clinically significant bleeding were similar in both groups. The data from RECOVERY were added to an updated meta-analysis that also included 8 previous trials of JAK inhibitors in people hospitalized with COVID-19. Mortality was 20% lower among those allocated to receive baricitinib or another JAK inhibitor.

Comment

The results of RECOVERY and previous clinical trials provide the basis for treatment guidelines (available at https://www.covid19treatmentguidelines.nih.gov and https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management) that recommend adding baricitinib to dexamethasone in patients hospitalized with COVID-19 who have rapidly increasing oxygen requirements or who require noninvasive or mechanical ventilation. The benefit of augmented immunomodulation, in which a second immunomodulatory agent is added to dexamethasone, has been proven for JAK inhibitors (especially baricitinib) and interleukin-6 inhibitors (particularly tocilizumab). Preliminary reports indicate that other immunomodulatory drugs may be beneficial, so the options are likely to expand.

Reviewing Author

Rajesh T. Gandhi, MD

Disclosures

Grant/Research SupportNIH

Editorial BoardsUpToDate; ID Images (idimages.org); Infectious Diseases Society of America COVID-19 Treatment Guidelines; International Antiviral Society–USA (Guidelines Committee)

Leadership Positions in Professional SocietiesHIV Medicine Association; Infectious Diseases Society of America (Board of Directors)