Janus kinases are intracellular enzymes that transmit signals arising from cytokine or growth factor receptor interactions on the cellular membrane to influence cellular processes of immune cell function and hematopoiesis. JAK-mediated signaling is pivotal in immune activation, as cytokine receptors are expressed on most immune cells. Within the signaling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription proteins (STATs), which modulate intracellular activity including gene expression. Baricitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs. Cytokine signaling is transmitted through pairing of JAKs. Baricitinib has greater affinity for JAK1, JAK2, and TYK2, relative to JAK3. In human leukocytes, baricitinib inhibits cytokine induced STAT phosphorylation mediated by JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, or JAK2/TYK2 with comparable potencies
Data regarding clinical efficacy for COVID-19 are being evaluated.
Safety Concerns:
- Thrombosis, including deep vein thrombosis (DVT) and pulmonary embolism (PE)
- Risk of GI perforation o Caution in patients with neutropenia, lymphopenia, and anemia
- Monitor for elevated liver function tests (LFTs)
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