Atopic dermatitis (AD) is a chronic, eczematous, severe pruritic skin disease. Sufficient knowledge regarding its pathogenesis is now facilitating the development of new drugs. Research results have revealed that Th2 cell-mediated immunity, skin barrier dysfunction and pruritus generate a vicious AD cycle. Conversely, the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway are also essential signaling pathways in various inflammatory diseases like AD. 

Precisely, TSLP, IL-4, IL-13 and IL-22 hold a vital position for Th2 cell-mediated immune reaction. Pan-JAK inhibitor also suppresses the STAT3 activation and improves the skin barrier function. Furthermore, TSLP, IL-4, IL-13 and IL-31 have also shown a vital role in chronic pruritus of AD, which gets transmitted via the JAK-STAT pathway. Therefore, JAK inhibitors serve as promising candidates for treating severe AD. 

A recent study reviews the clinical trials of topical dergocitinib (a pan-JAK inhibitor), ruxolitinib (a JAK1 and JAK2 inhibitor), and tofacitinib (a JAK1, JAK2 and JAK3 inhibitor) and oral baricitinib (a JAK1 and JAK2 inhibitor), abrocitinib and upadacitinib (JAK1 inhibitor). All the drugs showed significant improvements in the symptoms with a low frequency of adverse events. 

0.25% delgocitinib ointment has already demonstrated its effectiveness and safety in pediatric patients with AD and is now available for use in pediatric patients aged ≥2 years. Specifically, oral JAK inhibitors can improve pruritus and skin symptoms quickly. 

Thus, the emergence of these topical and oral JAK inhibitors is a remarkable innovation in treating AD.

Source: Nakashima C, Yanagihara S, Otsuka A. Innovation in the treatment of atopic dermatitis: Emerging topical and oral Janus kinase inhibitors. Allergol Int. 2022;71(1):40-6.