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Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID-19.
Pharmacotherapy. 2020 08; 40(8):843-856.P

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.

Authors+Show Affiliations

Department of Pharmacy, Sinai Health System, Toronto, Ontario, Canada.Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.Department of Pharmacy, Sinai Health System, Toronto, Ontario, Canada. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada. Antimicrobial Stewardship Program, University Health Network, Toronto, Ontario, Canada.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32542785

Citation

Jorgensen, Sarah C J., et al. "Baricitinib: a Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID-19." Pharmacotherapy, vol. 40, no. 8, 2020, pp. 843-856.
Jorgensen SCJ, Tse CLY, Burry L, et al. Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID-19. Pharmacotherapy. 2020;40(8):843-856.
Jorgensen, S. C. J., Tse, C. L. Y., Burry, L., & Dresser, L. D. (2020). Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID-19. Pharmacotherapy, 40(8), 843-856. https://doi.org/10.1002/phar.2438
Jorgensen SCJ, et al. Baricitinib: a Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID-19. Pharmacotherapy. 2020;40(8):843-856. PubMed PMID: 32542785.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID-19. AU - Jorgensen,Sarah C J, AU - Tse,Christopher L Y, AU - Burry,Lisa, AU - Dresser,Linda D, Y1 - 2020/07/27/ PY - 2020/6/17/pubmed PY - 2020/9/15/medline PY - 2020/6/17/entrez KW - COVID-19 KW - JAK-inhibitor KW - Janus-associated kinase inhibitor KW - SARS-CoV-2 KW - baricitinib KW - severe acute respiratory syndrome SP - 843 EP - 856 JF - Pharmacotherapy JO - Pharmacotherapy VL - 40 IS - 8 N2 - 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. SN - 1875-9114 UR - https://www.unboundmedicine.com/medline/citation/32542785/Baricitinib:_A_Review_of_Pharmacology_Safety_and_Emerging_Clinical_Experience_in_COVID_19_ L2 - https://doi.org/10.1002/phar.2438 DB - PRIME DP - Unbound Medicine ER -