Baricitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (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. 

JAK enzymes transmit cytokine signaling through their pairing (e.g., JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, JAK2/JAK2, JAK2/TYK2). In cell-free isolated enzyme assays, baricitinib had greater inhibitory potency at JAK1, JAK2 and TYK2 relative to JAK3. In human leukocytes, baricitinib inhibited cytokine induced STAT phosphorylation mediated by JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, or JAK2/TYK2 with comparable potencies. However, the relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.

OLUMIANT® is a Janus kinase (JAK) inhibitor indicated for:

• the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF blockers.

Limitations of Use: Not recommended for use in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine.

• the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECMO.
• the treatment of adult patients with severe alopecia areata.

Limitations of Use: Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants. 

Recommended Dosage:

Rheumatoid Arthritis:

• 2 mg once daily.
• OLUMIANT may be used as monotherapy or in combination with methotrexate or other non-biologic DMARDs.

COVID-19:

• 4 mg once daily for up to 14 days.

Alopecia Areata:

• 2 mg once daily. Increase to 4 mg once daily, if the response to treatment is not adequate.
• For patients with nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, consider treating with 4 mg once daily.
• Reduce the dose to 2 mg once daily when an adequate response has been achieved.

Dosage Modifications in Patients with Renal or Hepatic Impairment, or Cytopenias:

• See the full prescribing information for dosage modifications by indication.

Adverse reactions reported in clinical trials (≥1%) are:

• Rheumatoid Arthritis: upper respiratory tract infections (URTIs), nausea, herpes simplex, and herpes zoster.
• COVID-19: increases of liver enzymes, thrombocytosis, creatine phosphokinase increases, neutropenia, deep vein thrombosis, pulmonary embolism, and urinary tract infection (UTI).
• Alopecia Areata: URTIs, headache, acne, hyperlipidemia, creatine phosphokinase increase, UTI, liver enzyme elevations, folliculitis, fatigue, lower respiratory tract infections, nausea, genital Candida infections, anemia, neutropenia, abdominal pain, herpes zoster, and weight increase.

• Hypersensitivity: Serious reactions have been reported. Discontinue OLUMIANT if a serious hypersensitivity reaction occurs.
• Gastrointestinal Perforations: Monitor patients who may be at increased risk and evaluate promptly new onset of abdominal symptoms. 
• Laboratory Abnormalities: Monitor for changes in lymphocytes, neutrophils, hemoglobin, liver enzymes, and lipids. 
• Vaccinations: Avoid use with live vaccines.