Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID‐19

Abstract

A hyperinflammatory response to severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection, reminiscent of cytokine release syndrome, has been implicated in the pathophysiology of acute respiratory distress syndrome and organ damage in patients with coronavirus disease 2019 (COVID‐19). Agents that inhibit components of the pro‐inflammatory cascade have garnered interest as potential treatment options with hopes that dampening the proinflammatory process may improve clinical outcomes. Baricitinib is a reversible Janus‐associated kinase (JAK)‐inhibitor that interrupts the signaling of multiple cytokines implicated in COVID‐19 immunopathology. It may also have antiviral effects by targeting host factors that viruses rely for cell entry and by suppressing type I interferon driven angiotensin‐converting‐enzyme‐2 upregulation. However, baricitinib’s immunosuppressive effects may be detrimental during acute viral infections by delaying viral clearance and increasing vulnerability to secondary opportunistic infections. The lack of reliable biomarkers to monitor patients’ immune status as illness evolves complicates deployment of immunosuppressive drugs like baricitinib. Furthermore, baricitinib carries the risk of increased thromboembolic events, which is concerning given the proclivity towards a hypercoagulable state in patients with COVID‐19. In this article, we review available data on baricitinib with an emphasis on immunosuppressive and antiviral pharmacology, pharmacokinetics, safety, and current progress in COVID‐19 clinical trials.

Pharmaco-Immunomodulatory Therapy in COVID-19

“…remdesivir) and other drugs [38]. However, the use of baricitinib is associated with increased thromboembolic events, which is concerning given that COVID-19 patients are at risk of developing these events [39].…”

“…remdesivir) and other drugs [ 38 ]. However, the use of baricitinib is associated with increased thromboembolic events, which is concerning given that COVID-19 patients are at risk of developing these events [ 39 ]. In an Italian open-label study of 12 patients with moderate COVID-19 pneumonia [ 40 ], baricitinib therapy combined with lopinavir/ritonavir was associated with significant improvement in clinical and laboratory parameters, and none of the patients required intensive care unit support, however, the study was limited by its small sample size and open-label design.…”

JAK-STAT Pathway Inhibition and their Implications in COVID-19 Therapy

“…The side effects like headache, upper respiratory tract infection (UTI), nasopharyngitis are commonly seen in patients with Baricitinib therapy. The long term use of Baricitinib may increase the risks of developing serious infections and thromboembolic events in patients [ 112 ]. Consumption of Immunosuppressants concomitantly with Baricitinib was more likely prone to these infections.…”

Repurposing of Biologic and Targeted Synthetic Anti-Rheumatic Drugs in COVID-19 and Hyper-Inflammation: A Comprehensive Review of Available and Emerging Evidence at the Peak of the Pandemic

“…NCT04340232, NCT04358614, NCT04345289, NCT04399798, NCT04320277). These trials will also address safety concerns related to the reported increase in thromboembolic events associated with JAK inhibitors which may further increase the hypercoagulability risk inherent to COVID-19 ( Jorgensen et al, 2020 ; Tang Y. et al, 2020 ).…”