7.4 New developments in systemic treatment options
Many different cellular and molecular effectors are involved in AE. A recent review summarizes important players in type 2 immunity in regards to AE and Asthma [138]. The expanding knowledge of this complex type 2 immunological background of AE led to new developments of new cytokine-directed treatment options that are currently under investigation: Mepolizumab (anti-IL-5) treatment did not show an clinical improvement of AE patients in short and longterm phase-2 clinical trial [139]. Antibodies interfering with IL-13 (lebrikizumab, tralokinumab) have shown promising results in ongoing studies, while selective neutralization of IL-31 (nemolizumab) proved efficacy in reducing itch, but only moderate EASI response [75]. Several more biologics and small molecules interfering with key mediators of AE are currently in development and may contribute to tailored therapeutic approaches in future [75]. An interesting approach to improve AE in patients unresponsive to extensive therapy is, to use repetitive transient reductions of total IgE, which lead in a small number of patients to long‐lasting improvement of AE with improvement of both clinical parameters as well as the quality of life [140]. Additionally, downregulatory strategies for the immune system are under investigation. CD300a expression has a downregulatory role in AE (mice), thus could be an anti-inflammatory strategy [82]. The immune system in epithelial cells is posttranscriptional regulated by miRNAs [141]. Amongst others, miR-10a-5p has been identified to modulate AE targets [142]. L‐type amino acid transporter 1 (LAT1) is critical for activating human and mouse T cells and its inhibition reveals a potential new target for AE treatment [143].
It is important to increase the knowledge about the complex mechanisms influencing AE and therefore a combination of patient information correlated with biomaterial analysis and in vitro testing is needed. The CK-CARE program will contribute to identify and validate new and reliable biomarkers for precision medicine [144].