Baricitinib: A review of pharmacology, safety and emerging clinical experience in COVID‐19

CJ Jorgensen, Sarah; LY Tse, Christopher; Burry, Lisa; Dresser, Linda D

A hyperinflammatory response to 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 COVID‐19. Agents that inhibit components of the pro‐inflammatory cascade have garnered interest as potential treatment options with hopes that dampening the pro‐inflammatory 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 up regulation. 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 hyper‐coagulable state in COVID‐19 patients. 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.