Baricitinib for COVID-19
-
The FDA revised the emergency use authorization (EUA) for baricitinib (Olumiant, Lilly) to enable its use alone for the treatment of COVID-19 in hospitalized adults and pediatric patients as young as 24 months.
Under the revised EUA, baricitinib does not have to be administered with remdesivir (Veklury, Gilead). Baricitinib alone can be given to hospitalized adults and children with COVID-19 who require supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation.
The revision to the EUA was supported by data from a clinical trial of hospitalized patients with COVID-19, where baricitinib showed a reduction in the proportion of patients who died through 28 days of follow-up compared with patients treated with the standard of care for COVID-19 alone.
The COV-BARRIER study (ClinicalTrials.gov Identifier: NCT04421027) was a randomized, double-blind, placebo-controlled clinical trial of hospitalized adults with confirmed SARS-CoV-2 infection, which compared baricitinib 4 mg once daily (n=764) with placebo (n=761). Patients could remain on standard of care, as defined per local guidelines, including antimalarials, antivirals, corticosteroids and/or azithromycin. The most frequently used background treatments were corticosteroids (79%) and remdesivir (19%).
The mean age of the patients was 58 years, and 33% were older than 65. Most of the patients were men and only 5% were Black. Most (96.3%) required supplemental oxygen, and 24% required noninvasive ventilation or high-flow oxygen. Many had comorbidities including hypertension (48%), obesity (33%) and type 2 diabetes (29%). Demographics and disease characteristics were similar across both groups.
The primary end point was the proportion of patients who died or progressed to noninvasive ventilation/high-flow oxygen or invasive mechanical ventilation within the first 28 days of the study. Patients who required noninvasive ventilation/high-flow oxygen at baseline needed to worsen by at least 1 point on an 8-point ordinal scale to progress. A key secondary end point was all-cause mortality by day 28.
The estimated proportion of patients who died or progressed to noninvasive ventilation/high-flow oxygen or invasive mechanical ventilation was lower in those treated with baricitinib (27.8%) compared with placebo (30.5%), but this effect was not statistically significant (odds ratio; 0.85; 95% CI, 0.67-1.08; P=0.180).
The proportion of patients who died by day 28 was 8.1% (62/764) for baricitinib versus 13.3% (101/761) for placebo.
While this revised EUA no longer requires baricitinib to be administered with remdesivir, the use of baricitinib in combination with remdesivir is not contraindicated under the terms and conditions of this authorization.
Remdesivir is approved to treat COVID-19 in hospitalized adults and pediatric patients (≥12 years of age and weighing ≥40 kg) requiring hospitalization. Remdesivir also remains authorized for emergency use for the treatment of COVID-19 in hospitalized pediatric patients weighing from 3.5 to less than 40 kg or hospitalized pediatric patients younger than 12 years of age weighing at least 3.5 kg.
