JAK-inhibitors, atopic dermatitis

Atopic dermatitis is one of the most serious global problems (Miao M et al. Miao M et al. (2021) 2021), affecting around 15-30% of children and 10% of adults in industrialized countries. AD has a significant impact on physical and mental well-being. It ultimately impairs health-related quality of life and thus increases healthcare costs.

The Janus kinase (JAK) family is a group of cytoplasmic tyrosine kinases that mediate signaling pathways activated by various cytokines. By influencing the JAK-STAT signaling pathway, JAK1 is involved in numerous processes of cell proliferation and differentiation. Janus kinases phosphorylate and activate signal transducers and transcriptional activators (STATs), which in turn modulate intracellular activity, including gene expression. Inhibition of JAK1 modulates these signaling pathways by preventing the phosphorylation and activation of STATs.

JAK inhibitors have been used with good success in the treatment of AD (Arora CJ et al. 2020; Miao M et al. 2021). A number of clinical studies have shown that oral and topical JAK inhibitors have the potential to significantly improve the clinical outcomes of adult or adolescent AD patients who respond inadequately to conventional treatments (Gadina M et al. 2019; Honstein T et al. 2020; Tsai HR et al. 2021). In a network meta-analysis, upadacitinib proved to be superior to abrocitinib and baricitinib. On the other hand, abrocitinib proved to be superior to the JAK inhibitor baricitinib. In addition, the different dosing regimens showed that upadacitinib at a dose of 30 mg was superior to all other regimens. Upadacitinib 15 mg was superior to the other JAK inhibitors with the exception of abrocitinib 200 mg. Abrocitinib 200 mg was superior to abrocitinib 100 mg and baricitinib at different doses (Wan H et al. (2022).

1. Arora CJ et al. (2020) The effectiveness of Janus kinase inhibitors in treating atopic dermatitis: a systematic review and meta-analysis. Dermatol Ther 33:e13685.
2. Bieber T et al. (2021) Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med 384: 1101-1112.
3. Gadina M et al. (2019) Janus kinases to jakinibs: from basic insights to clinical practice. Rheumatology. 58(Suppl 1): i4-i16.
4. Honstein T et al. (2020) The show must go on: an update on clinical experiences and clinical studies on novel pharmaceutical developments for the treatment of atopic dermatitis. Curr Opin Allergy Clin Immunol 20: 386-394.
5. Langan SM et al.(2020) Atopic dermatitis. Lancet 396: 345-360.
6. Miao M et al. (2021) The efficacy and safety of JAK inhibitors for atopic dermatitis: a systematic review and meta-analysis. J Dermatolog Treat 27: 1-9.
7. Shreberk-Hassidim R et al. (2017) Janus kinase inhibitors in dermatology: a systematic review. J Am Acad Dermatol 76: 745-753.
8. Silverberg JI et al. (2013) Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study. J Allergy Clin Immunol 132: 1132-1138.
9. Tsai HR et al. (2021) Application of Janus kinase inhibitors in atopic dermatitis: an updated systematic review and meta-analysis of clinical trials. J Pers Med 11: 279.