Baricitinib combination therapy: a narrative review of repurposed Janus kinase inhibitor against severe SARS-CoV-2 infection

Abstract

Purpose The Coronavirus disease 2019 (COVID-19) pandemic is one of the most devastating global problems. Regarding the lack of disease-specific treatments, repurposing drug therapy is currently considered a promising therapeutic approach in pandemic situations. Recently, the combination therapy of Janus kinase (JAK) inhibitor baricitinib has been authorized for emergency COVID-19 hospitalized patients; however, this strategy's safety, drug-drug interactions, and cellular signaling pathways remain a tremendous challenge. Methods In this study, we aimed to provide a deep insight into the baricitinib combination therapies in severe COVID-19 patients through reviewing the published literature on PubMed, Scopus, and Google scholar databases. We also focused on cellular and subcellular pathways related to the synergistic effects of baricitinib plus antiviral agents, virus entry, and cytokine storm (CS) induction. The safety and effectiveness of this strategy have also been discussed in moderate to severe forms of COVID-19 infection. Results The severity of COVID-19 is commonly associated with a dysregulated immune response and excessive release of pro-inflammatory agents, resulting in CS. It has been shown that baricitinib combined with antiviral agents could modulate the inflammatory response and provide a series of positive therapeutic outcomes in hospitalized adults and pediatric patients (age ≥ two years old). Conclusion Baricitinib plus the standard of care treatment might be a potential strategy in hospitalized patients with severe COVID-19.

Initiation of Tocilizumab or Baricitinib Were Associated With Comparable Clinical Outcomes Among Patients Hospitalized With COVID-19 and Treated With Dexamethasone

“…With respect to viral dynamics, no significant differences in time to low viral load or positive IgG antibody were identified between treatment groups, which might be attributed to their comparable initial viral load, and antibody response was not impaired by either drug ( Bronte et al, 2020 ; Masiá et al, 2020 ). While tocilizumab use was associated with a shorter time to viral clearance of marginal significance, further studies directly comparing tocilizumab and baricitinib in COVID-19 patients are needed to delineate their effects on SARS-CoV-2 RNA shedding, as the current literature is limited with inconclusive evidence on the association between the use of these immunomodulatory drugs and viral clearance, which is further complicated by the diverse clinical characteristics of COVID-19 patients (including but not limited to their age, albumin level, initial viral load, disease severity, and immunocompetence) ( Masiá et al, 2020 ; Akbarzadeh-Khiavi et al, 2021 ; Cogliati Dezza et al, 2021 ).…”

Baricitinib: A Review in Moderate to Severe Atopic Dermatitis

“…2 ) could be considered an impediment to treating a viral infection (e.g. COVID-19), with IFNs preventing virus replication during the early stage of an infection, such an action may alleviate the hyper-inflammation (resulting from excessive cytokine production) seen with severe COVID-19, and therefore improve clinical outcomes [ 38 ].…”

The effect of various compounds on the COVID mechanisms, from chemical to molecular aspects

“…Recently, the combination therapy of Janus kinase (JAK) inhibitor baricitinib has been granted emergency use authorization for COVID-19 hospitalized patients [ 158 ]. Emanuelle Machado Marinho et.al in their study showed that baricitinib can interact powerfully with the Mpro.…”