Atopic dermatitis (AD) is known as a chronic, systemic, inflammatory condition affecting the skin which has telltale signs of persistent itch and marked redness. While AD is associated with an increased risk of infections and poor quality of life, the existing therapy options were not aimed at selectively targeting disease-causing pathways that have been already known for this indication. Topical therapies provide limited efficacy, while corticosteroids and immunosuppressants have tolerability issues.

The established pathophysiology of AD has shown an inappropriate activation of 2T helper cells (Th2) cells and type 2 innate lymphoid (ILC2) cells, with a major increase in type 2 cytokines in the skin including interleukin-13 and interleukin-4. IL-13 and I-4 are implicated in tissue inflammation and epidermal barrier dysfunction. Monoclonal antibodies targeting IL-13 and IL-4 are currently in clinical development.

Dupilumab, a human anti-IL-4Rα-antibody, is the first biologic which was approved by FDA in 2017 for the treatment of moderate to severe AD. The anti-IL-13 antibodies lebrikizumab and tralokinumab, bind to different IL-13 epitopes and show potentially different effects, and are currently in advanced-stage trials.

The significance of IL-4Rα in disease pathophysiology and thereby the cytokines IL-4 and IL-13 which employ the receptors for signalling is well established in AD. However, there are conflicting opinions about the cytokine, which is most central to the pathobiology of AD or if inhibiting the cytokine will lead to clinical response. However, the initial success achieved with the drugs lebrikizumab and tralokinumab is indicative of the fact that IL-13 blockade may be adequate for getting an effective clinical response in AD patients.

Reference: Moyle M, cevikbas F, Harden JL, Guttman-Yassky E. Understanding the immune landscape in atopic dermatitis: the era of biologics and emerging therapeutic approaches. Exp Dermatol. 2019; 28(7): 756-768.