Itching for innovation: role of aryl hydrocarbon receptor agonists as a future therapy for atopic dermatitis

Abstract Atopic dermatitis (AD) is a chronic, inflammatory skin condition which affects over 200 million people worldwide, with patients commonly presenting with dry, itchy and sore skin. The challenge in finding optimal treatment for AD stems from the heterogenous nature of the disease and its multifaceted aetiology: skin barrier dysfunction, immune system dysregulation, genetic factors, environmental factors and alterations in skin microorganisms. Traditional treatments for AD such as corticosteroids, calcineurin inhibitors and immunosuppressants have several limitations such as reoccurrence of symptoms when discontinued, lack of targeted action and risk of adverse effects. The aim of this literature review was to explore and summarise the role of aryl hydrocarbon receptor (AHR) agonists (namely Tapinarof) as potential future therapy for AD. AHR agonists hope to overcome the limitations of traditional AD therapies and exert their therapeutic value by maintaining integrity of the skin barrier, defending against oxidative stress, modulating immune activity and inflammation and restoring a healthy skin microbiome. Tapinarof, a topical AHR agonist, is showing promising results and is currently in phase 3 trials (ADORING 3). For Tapinarof to be integrated into the AD treatment pathway, further research must be conducted on its efficacy, durability, potential remittive effect and safety across different AD subtypes in a large, diverse patient population. In addition, Tapinarof’s cost-effectiveness compared to its topical counterparts needs to be considered and multidisciplinary collaboration is required between researchers, clinicians and policy makers.