Atopic dermatitis (AD)
Atopic dermatitis (AD) is a chronic relapsing skin condition characterised by intense itching (pruritus), a defective skin-barrier and a T-cell mediated inflammation.
The involvement of a range of T cell sub-types in the progression of AD is outlined in the adjacent figure. Specifically implicated in disease progression are the Th2, Th22, Th17 and Th1 pathways which drive the skin pathology which is characteristic of both acute and chronic lesions of AD.
The prevalence of AD is estimated at 15-30% in children and 2-10% in adults, with incidence increasing in the developed world. It is a disease that significantly affects the quality of life of patients and their families and there is a strong association between AD and mental health disorders.
Therapy for AD focuses on the use emollients, to maintain the skin’s barrier function, and the topical immunotherapies, corticosteroids and calcineurin inhibitors. Although effective, both treatments have safety issues associated with long term use.
In addition, compliance with these topical therapies is generally low and although new topical drugs will soon be available compliance issues will remain.
In more severe AD, systemic corticosteroids and calcineurin inhibitors are used and although they can control the disease side-effects preclude chronic use.
Oral CRAC inhibitor
There is therefore a clear unmet medical need for safe and effective systemic therapies for the long-term management of AD.
Pre-clinical studies have demonstrated that CRAC inhibitors effectively suppress the release of T cell cytokines implicated in the progression of AD and show oral efficacy in models of AD.
An oral CRAC inhibitor will target both mast and T-cell activation and should provide an efficacious and safe therapy to address the high unmet medical need in moderate to severe AD.