See important safety information, including boxed warning, in the attached prescribing information.

Rheumatoid arthritis is associated with an abnormal production of pro-inflammatory cytokines and growth factors.1-3 Many pro-inflammatory cytokines, including interleukin (IL)-2, IL-6, IL-12, interferon (IFN)-alpha, IFN-beta, and IFN-gamma, and granulocyte/macrophage colony-stimulating factor (GM-CSF), require members of the Janus kinase (JAK) family of protein tyrosine kinases (JAK1, JAK2, JAK3, and tyrosine kinase [TYK] 2) to transduce signals across cell membranes.2,4-6

Inside the cell, JAKs facilitate the transfer of a phosphate group from adenosine triphosphate (ATP) to signal transducers and activators of transcription (STATs) via autophosphorylation and transphosphorylation.6 This reversible phosphorylation activates the STATs and allows them to

• move to the nucleus of the cell, bind to deoxyribonucleic acid and other gene regulatory proteins, and
• activate the transcription of genes involved in inflammation.4,6-8

The inhibition of one or more JAKs modulates the activity of the associated JAK-dependent cytokines.2,5

Baricitinib is a selective and reversible inhibitor of the JAK family of protein tyrosine kinases, specifically JAK1 and JAK2, with less selectivity for TYK2 and JAK3.2,5

Baricitinib modulates the JAK-STAT pathway, and, consequently, signaling by cytokines including IL-6, IFN, and GM-CSF, by transiently occupying the ATP binding pocket of the JAK. This prevents the phosphorylation of JAKs and the subsequent phosphorylation and activation of STATs.6,9

Janus kinase enzymes transmit cytokine signaling through their pairing, such as JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, JAK2/JAK2, JAK2/TYK2. In human leukocytes, baricitinib inhibited cytokine induced STAT phosphorylation mediated by JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, or JAK2/TYK2 with comparable potencies.9

Janus kinase inhibition by baricitinib is transient and reversible.5 Baricitinib inhibits signaling through the JAK-STAT pathway for a portion of the day. Maximal inhibition occurs at 1 to 2 hours postdose and returns to baseline by 16 to 24 hours.2 

In isolated enzyme assays, baricitinib exhibited

• selectivity for JAK1 with an IC₅₀ (half maximal inhibitory concentration) of 5.9 nM and JAK2 with an IC₅₀=5.7 nM
• 100-fold less selectivity for JAK3 with an approximate IC₅₀  of 560 nM, and
• 10-fold less selectivity for TYK2 with an IC₅₀ of 53 nM.5

The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.9

Baricitinib has

• an empirical formula of C₁₆H₁₇N₇O₂S,
• a molecular weight of 371.42, and 
• the structural formula as shown in Baricitinib Structural Formula.9

OLUMIANT® (baricitinib) tablets, for oral use, Lilly

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).