Janus kinase inhibitors for the therapy of atopic dermatitis

Abstract

The JAK-STAT pathway is involved in the signaling of multiple cytokines driving cutaneous inflammation in atopic dermatitis (AD). Janus kinase (JAK) inhibitors target individual receptor-associated kinases, thereby preventing the mediation of inflammatory signals. Several JAK inhibitors with varying mechanism of action, potency, and safety represent potential therapeutic options for AD in both topical and systemic application. The JAK1/2 selective JAK inhibitor baricitinib was the first substance from this class of drugs approved by the EMA for the systemic oral treatment of AD. The clinical development program of the JAK1 selective inhibitors upadacitinib and abrocitinib is finalized with positive results for AD. The PAN-JAK inhibitor delgocitinib was the first substance being approved for the treatment of AD (in Japan). This review article covers the rising data on investigational and approved JAK inhibitors in the context of the treatment of AD.

Keywords: JAK inhibitors; atopic dermatitis; baricitinib; cerdulatinib; delgocitinib; ruxolitinib; upadacitinib; ­tofacitinib.

Figure 1.. Cytokine receptors and their associated Janus kinases (JAKs). The different cytokines and growth factors bind to receptors associated with different JAKs. The different JAK inhibitors inhibit different JAKs, resulting in a diverse spectrum of activity. GM-CSF = granulocyte-macrophage colony stimulating factor; EPO = erythropoietin; IFN = interferon; TPO = thrombopoietin; TSLP = thymic stromal lympho­poietin.