OX40/OX40L modulation: A target for regulating T cells in cutaneous inflammatory disorders

The aetiology of many inflammatory cutaneous diseases is T cell-driven and involves dysregulation of the immune response. The complex nature of the immune system's involvement in these diseases has made the development of effective, safe, and durable treatments challenging, resulting in a continued demand for the development of novel therapeutics. OX40 and its ligand OX40L have been previously identified as a crucial axis in T cell differentiation and function, and are promising targets for the treatment of T cell-driven disease. Development of OX40/OX40L agonists and inhibitors has potential uses in atopic dermatitis, alopecia areata, psoriasis, and more. While trials of these drugs have mainly been conducted in atopic dermatitis, they show promise in treating other dermatological conditions. Studies of amlitelimab and rocatinlimab have shown some efficacy but have demonstrated increased durability of response. Current concerns with the class are the potential for broad immune suppression with antagonists and the potential for worsening disease with agonists. Additional studies will enable us to determine their benefit-risk ratio in the real-world setting.