JAK/STAT inhibitors for the treatment of atopic dermatitis

Introduction: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Lesional skin of AD contains elevated levels of Th2, Th17, Th22 and Th1-citokines. With a growing movement toward use of targeted therapies, parallel to psoriasis, JAK inhibitors are an important focus of therapeutic research for AD. Methods: We review current evidence on the efficacy and safety of oral and topical JAK inhibitors for the treatment of AD. Results: Several JAK inhibitors are in phase II and III clinical trials as oral therapies for moderate-to-severe AD or as topical treatments for mild-to-moderate AD. Results thus far are encouraging, with the majority of the patients achieving the primary outcome of their trial as well as a favorable safety profile. Discussion: JAK inhibitors will most certainly be the first oral targeted option when topical therapy fails. With good oral bioavailability and lack of immunogenicity, they address some of the limitations of biologics. Yet to be defined is whether selective JAK 1 inhibitors or nonselective JAK inhibitors will provide the best equilibrium of efficacy versus side effects. Less clear is the position in the therapeutic ladder for topical JAK inhibitors; although, an unmeet need exists in the topical treatment of AD.