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

Atopic dermatitis (AD) is a chronic, inflammatory skin condition that affects over 200 million people worldwide. Patients commonly present with dry, itchy and sore skin. The challenge in finding optimal treatment for AD stems from the heterogeneous 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 the reoccurrence of symptoms when discontinued, lack of targeted action and risk of adverse effects. The aim of this literature review was to explore and summarize the role of aryl hydrocarbon receptor (AHR) agonists (namely tapinarof) as potential future therapy for AD. It is hoped that AHR agonists will overcome the limitations of traditional AD therapies and exert their therapeutic value by maintaining the 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 has recently concluded its long-term extension phase III trial (ADORING 3). For tapinarof to be integrated into the AD treatment pathway, robust research evidence must be presented on its efficacy, durability, potential remittive effect and safety across different AD subtypes in a large, diverse patient population. In addition, the cost-effectiveness of tapinarof compared with its topical counterparts needs to be considered and multidisciplinary collaboration is required between researchers, clinicians and policymakers.