Atopic dermatitis (AD) is characterized by intense itch and recurrent eczematous lesions.
Interleukin (IL)-33 is constitutively produced from the structural and lining cells, including skin epithelial cells, which are exposed to the environment. Extracellular IL-33 binds to ST2 on T helper 2 (Th2) cells, mast cells, eosinophils, and innate lymphoid cells. 
In patients with AD, IL-33 overexpression in the epidermis, infiltration of ST2-positive cells, and elevated serum IL-33 levels has been implicated in disease pathogenesis.1,2 Transgenic mice with constitutive epidermal-specific IL-33 expression (IL-33tg) spontaneously develop a progressive, AD-like skin inflammation and pruritus.3,4 
The Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway is involved in 
AD-related cytokine signaling, including IL-33, mediating downstream inflammation and barrier alterations. Ruxolitinib cream, a topical JAK1/JAK2 inhibitor, is currently being evaluated in clinical trials for the treatment of mild to moderate AD (NCT03011892, NCT03745651, NCT03745638).
Our goal was to evaluate ruxolitinib cream as a monotherapy for the treatment of pruritus in the spontaneous-onset IL-33 transgenic mouse model of AD.
Animals were randomized to four treatment groups; vehicle cream (twice daily [b.i.d.]), ruxolitinib cream 1.5% (b.i.d), topical steroid (clobetasol 0.05% once daily [q.d.]) and vehicle-treated (b.i.d) non-transgenic littermates. Scratching and grooming analysis was performed at 14 and 24 weeks of age. Skin inflammation and mast cell frequency were quantified by histology. Tissue biopsies were analyzed for JAK-STAT pathway modulation and disease pathogenesis markers.
Ruxolitinib cream 1.5% (b.i.d.) treatment demonstrated sustained amelioration of pruritus (p < 0.05) and abnormal grooming behaviors (p < 0.001) at 14 and 24 weeks of age. Chronic topical administration of ruxolitinib cream was well tolerated in the IL-33tg mice.
Together, these data support the scientific rationale that ruxolitinib cream, a topical JAK1/JAK2 inhibitor, may have potential as a therapeutic agent for the treatment of AD.

Ruxolitinib cream ameliorates spontaneous atopic dermatitis in the IL-33 transgenic mouse model