Janus kinase inhibitors for atopic dermatitis: a promising treatment modality

Abstract

Summary Atopic dermatitis (AD) is chronic, pruritic, inflammatory skin disease that affects a significant portion of the population in industrialized nations. For nonresponders to conventional therapies, AD can significantly reduce sleep quality and quality of life. AD pathogenesis is multifactorial and involves multiple immune pathways, with recent evidence of T helper (Th)2, Th17 and Th22 axis attenuation in various AD endotypes and racial subtypes. Inhibition of the conserved Janus kinase (JAK) signalling pathway represents a promising therapeutic avenue to reduce the activation of multiple proinflammatory mediators involved in AD pathogenesis. JAK inhibitors exist in both oral and topical forms with variable specificity for the receptor tyrosine kinases JAK1, JAK2, JAK3 and tyrosine kinase 2. Oral formulations include abrocitinib, upadacitinib, baricitinib and gusacitinib, and are most appropriate for patients with moderate to severe AD. Emerging topical formulation in development include ruxolitinib and deglocitinib, which may be used in patients with localized AD and also adjunctively with systemic therapy in patients with more severe disease. With observed rapidity in itch relief and accompanying dramatic reduction in inflammatory lesion count, JAK inhibitors represent a promising new treatment to revolutionize the management of AD.

Pruritus as a Distinctive Feature of Type 2 Inflammation

“…Oral formulations include abrocitinib, upadacitinib, baricitinib, and gusacitinib, and are suitable to treat moderate-to-severe AD. Topical formulations include ruloxitinib, beprocitinib, and delgocitinib [77].…”

Current Insights into Immunology and Novel Therapeutics of Atopic Dermatitis

“…Thus, the dual inhibition of JAK and SYK can widen the range of targeted cytokines and increase the clinical efficacy of JAK inhibition by resolving different subtypes of AD. Clinical trials with gusacitinib have indicated good tolerability and significant reduction in pruritus and inflammatory lesion count [199,200].…”

From Emollients to Biologicals: Targeting Atopic Dermatitis

“…A novel frontier in the treatment of AD is represented by JAK-inhibitors, small molecules that can be used both in the topical formulation thanks to their low molecular weight (about 300 kDa lower than the skin barrier threshold), and in the systemic oral formulation [ 119 , 120 ]. These include delgocitinib, ruxolitinib, and tofacitinib as topic formulations, baricitinib, upadacitinib, abrocitinib, and gusacitinib as systemic drugs [ 121 , 122 ]. Delgocitinib (pan-JAK-inhibitor) in ointment formulation improved clinical signs and symptoms in children and in adults with AD and it was well tolerated [ 123 , 124 , 125 ].…”