In hospitalized patients with COVID-19, baricitinib — used in combination with dexamethasone and/or an anti–interleukin 6 (IL-6) inhibitor — has been shown to be an effective treatment option, with favorable results reported regarding reduced rates of mortality, shortened duration of hospitalization, and early hospital discharge. Findings of a meta-analysis of randomized controlled trials (RCTs) on the topic were recently published in the journal eClinical Medicine.

Baricitinib, a Janus kinase 1/2 inhibitor with anti-inflammatory and anti-viral properties, was initially approved for treatment of rheumatoid arthritis. Investigators for the current study sought to evaluate the effect of baricitinib in patients hospitalized with COVID-19 via a meta-analysis of RCTs. The researchers conducted a literature search through March 31, 2022, with the following outcomes evaluated: (1) 28-day mortality; (2) progression to invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO); (3) progression to respiratory failure requiring positive pressure ventilation, IMV, or death; (5) duration of hospital stay; and (6) time to hospital discharge.

The analysis included 4 RCTs with a total of 10,815 patients: ACTT-2 (ClinicalTrials.gov Identifier: NCT04401579), COV-BARRIER and COV-BARRIER–severe (both ClinicalTrials.gov Identifier: NCT04421027), and RECOVERY (ClinicalTrials.gov Identifier: NCT04381936). According to the results of a pooled analysis with the use of a random-effects model, treatment with baricitinib was associated with a statistically significant reduction in 28-day mortality (odds ratio [OR], 0.69; 95% CI, 0.50-0.94; P =.04). A significant reduction in the composite outcome of progression to severe disease requiring positive pressure ventilation, IMV, or death was also reported with baricitinib therapy (OR, 0.89; 95% CI, 0.80-0.99: P =.03).


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A favorable trend toward reduced progression to IMV or ECMO was observed among patients treated with baricitinib compared with those receiving standard therapy, but this finding was not statistically significant (OR, 0.76; 95% CI, 0.58-1.01; P =.06).

Certain limitations of this meta-analysis should be noted. The number of patients enrolled in the RECOVERY trial was much higher than in the other 3 RCTs. Further, variations exist with respect to enrollment criteria, heterogeneity of clinical practice across different geographic locales, and differences in the measurement of clinical progression.

The researchers concluded that future studies are warranted to evaluate the effect of baricitinib at higher doses or with a standard loading dose to prevent progression events. Consideration might also be afforded to head-to-head trials and platform trials that compare the efficacy of baricitinib with that of the IL-6 inhibitor tocilizumab, in addition to the use of baricitinib with or without the use of other immunomodulators.

Reference  

Selvaraj V, Finn A, Lal A, Khan MS, Dapaah-Afriyie K, Carino GP. Baricitinib in hospitalised patients with COVID-19: a meta-analysis of randomised controlled trials. eClinicalMedicine. Published online June 3, 2022. doi:10.1016/j.eclinm.2022.101489