Jak-stat signal path

Important signal transduction mechanism that contributes to the regulation of cell development. The JAK-STAT signalling pathway provides a means for cells to transmit the information of extracellular signalling peptides from the cell membrane to the promoters of target genes in the nucleus.

The JAK-STAT pathway was originally discovered during the treatment of cells with interferons, which are secreted in particular by leukocytes in response to viral infections. From the group of cytokines, besides interferons, interleukins, and from the group of hormones, erythropoietin, prolactin and growth hormone are classical ligands for the cytokine receptors involved.

The naming of the signalling cascades was derived from JAK (= acronym for "Janus kinases or also - just another kinase") and STAT (= acronym for "Signal Transducers and Activators of Transcription").

Baricitinib is an oral selective JAK1 and JAK2 inhibitor. The active substance was investigated in a phase 2 and several phase 3 studies in adults with moderate to severe atopic dermatitis at a dose of 1 mg, 2 mg and 4 mg once daily compared to placebo. This showed a significant improvement in the EASI score from baseline to 16 weeks, particularly at the two higher doses, 2 mg daily (mean difference -5.6 points; CI 95%: 0.4-10.9 [GRADE assessment: moderate safety]) and 4 mg daily (mean difference -5.2 points; CI 95%: 0.1-10.4 [GRADE assessment: moderate safety]) (Drucker AM et al. (2020). Baricitinib, like all JAK inhibitors, is a fast-acting drug

Experimental: use of Janus kinase inhibitors in alopecia areata.

see further indications

1. Drucker AM et al. (2020) Systemic Immunomodulatory Treatments for Patients With Atopic Dermatitis: A Systematic Review and Network Meta-analysis. JAMA Dermatol 156:659-667.

2. Pieri L et al. (2014) Ruxolitinib-Induced Reversal of Alopecia Universalis in a Patient with Essential Thrombocythemia. Am J Hematol 2014 doi: 10.1002/ajh.23871.
3. Xing L et al. (2014) Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med 20:1043-1049