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

Alopecia areata (AA) is an autoimmune hair loss disorder causing well-defined coin-shaped patches of non-scarring hair loss. Hair loss ranges from single well-defined patches to multiple discrete or overlapping patches to a loss of hair in all hair-bearing sites known as alopecia universalis. Alopecia areata has a complex etiology with an unpredictable disease course.1

In AA, the cyclical nature of hair growth is disrupted.1 This is believed to result from loss of hair follicle immune privilege, a complex mechanism that normally

• suppresses inflammation, and
• promotes immune tolerance in the hair follicle.2-4

Loss of immune privilege allows immune cells such as natural killer (NK) cells and CD8+ T cells to infiltrate the hair follicle leading to an inflammatory swarm around the hair bulb. This is accompanied by

• a marked interferon-gamma (IFN-γ) response, and
• up regulation of gamma-chain cytokines (interleukin [IL]-15, IL-2, IL-7, and IL-21).5,6 

This response activates the janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway.5,6

The JAK-STAT pathway is activated when ligand binding induces the dimerization of receptor subunits. Receptor-associated JAKs then bind adenosine triphosphate (ATP) and become active. Subsequent activation of STAT transcription factors, which translocate to the nucleus, regulate the transcription of genes involved in the production of pro-inflammatory cytokines responsible for disease maintenance in alopecia areata.5-8 

Baricitinib is a selective and reversible inhibitor of the JAK family of protein tyrosine kinases, specifically JAK1 and JAK2, with less selectivity for tyrosine kinase 2 (TYK2) and JAK3.9,10

Baricitinib modulates the JAK-STAT pathway, and, consequently, signaling by cytokines, by transiently occupying the ATP binding pocket of the JAK. This inhibits the phosphorylation of JAKs and the subsequent phosphorylation and activation of STATs.11,12

Janus kinase inhibition by baricitinib is transient and reversible.9 Baricitinib inhibits signaling through the JAK-STAT pathway for a portion of the day. Maximal inhibition occurs at 1 to 2 hours post dose and returns to baseline by 16 to 24 hours.10 

Please click on the video links below for a visual representation of the mechanism of action of baricitinib in AA.

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, with comparable potencies, mediated by 

• JAK1/JAK2
• JAK1/JAK3
• JAK1/TYK2, or
• JAK2/TYK2.12

In biochemical assays that determined the concentration necessary to inhibit 50% of enzyme activity (IC₅₀), baricitinib exhibited

• selectivity for JAK1 with an IC₅₀ of 5.9 nM and JAK2 with an IC₅₀ of 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.9

The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is currently not known.12

Baricitinib has

• an empirical formula of C₁₆H₁₇N₇O₂S,
• a molecular weight of 371.42, and 
• the structural formula as shown in Baricitinib Structural Formula.12

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

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