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Olumiant® (baricitinib) tablets
1mg, 2mg, 4mgbaricitinib
1mg, 2mg, 4mgOlumiant® (baricitinib) tablets
1mg, 2mg, 4mgbaricitinib
1mg, 2mg, 4mgThis information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What is the mechanism of action of Olumiant® (baricitinib) in alopecia areata?
Alopecia areata results from the loss of hair follicle immune privilege, allowing immune cells to infiltrate the follicle and activate the JAK-STAT pathway. Baricitinib is a selective and reversible inhibitor of JAK proteins, specifically JAK1 and JAK2.
See important safety information, including boxed warning, in the attached prescribing information.
The Role of Cytokines and Janus Kinases in Alopecia Areata
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
Mechanism of Action of Baricitinib in Alopecia Areata
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
Selectivity of Baricitinib
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.
Structural Description of Baricitinib
Baricitinib has
- an empirical formula of C16H17N7O2S,
- a molecular weight of 371.42, and
- the structural formula as shown in Structural Formula of Baricitinib.13
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Pratt CH, King LE Jr, Messenger AG, et al. Alopecia areata. Nat Rev Dis Primers 2017;3:17011. https://doi.org/10.1038/nrdp.2017.11
2Ito T. Recent advances in pathogenesis of autoimmune hair loss disease alopecia areata. Clin Dev Immunol. 2013;2013:348546. https://doi.org/10.1155/2013/348546
3Paus R, Bulfone-Paus S, Bertolini M. Hair follicle immune privilege revisited: the key to alopecia areata management. J Investig Dermatol Symp Proc. 2018;19(1):S12-S17. https://doi.org/10.1016/j.jisp.2017.10.014
4Azzawi S, Penzi LR, Senna MM. Immune privilege collapse and alopecia development: is stress a factor? Skin Appendage Disord. 2018;4(4):236-244. https://doi.org/10.1159/000485080
5Triyangkulsri K and Suchonwanit P. Role of janus kinase inhibitors in the treatment of alopecia areata. Drug Des Devel Ther. 2018;12:2323-2335. https://doi.org/10.2147/dddt.s172638
6Divito SJ, Kupper TS. Inhibiting Janus kinases to treat alopecia areata. Nat Med. 2014;20(9):989-990. https://doi.org/10.1038/nm.3685
7McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011:8;365(23):2205-2219. https://doi.org/10.1056/nejmra1004965
8O’Shea JJ, Schwartz DM, Villarino AV, et al. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med. 2015;66:311-328. http://dx.doi.org/10.1146/annurev-med-051113-024537
9Fridman JS, Scherle PA, Collins R, et al. Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J Immunol. 2010;184(9):5298-5307. http://dx.doi.org/10.4049/jimmunol.0902819
10Shi JG, Chen X, Lee F, et al. The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 1/2 inhibitor, in healthy volunteers. J Clin Pharmacol. 2014;54(12):1354-1361. http://dx.doi.org/10.1002/jcph.354
11Schwartz DM, Bonelli M, Gadina M, O’Shea JJ. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol. 2016;12(1):25-36. http://dx.doi.org/10.1038/nrrheum.2015.167
12Olumiant [package insert]. Indianapolis, IN: Eli Lilly and Company; 2026.
13Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Date of Last Review: September 09, 2026