IL-13 inhibition in the treatment of atopic dermatitis - new and emerging biologic agents

Abstract

Atopic dermatitis (AD) is a common, chronic, and recurrent inflammatory skin condition that affects a considerable portion of the population, and is particularly prevalent among children. The development of AD is influenced by environmental and genetic factors, which cause epidermal barrier dysfunction, immune dysregulation, and dysbiosis. In immune dysregulation, there is excessive production of cytokines. Among the cytokines, interleukin (IL)-13 plays a major role in the pathogenesis of AD. Searching for new and more selective treatments for moderate-to-severe cases is important because of the considerable effect of AD on the quality of life. Tralokinumab and lebrikizumab are selective IL-13 inhibitors that have demonstrated safety and efficacy as treatment options for AD in phase III trials. Tralokinumab is approved for use in Europe and the USA, while lebrikizumab is approved only in Europe. Cendakimab, which is another IL-13 selective inhibitor, has shown promising results in phase II trials, providing safe and effective outcomes. Eblasakimab, which disrupts IL-13 and IL-4 signaling pathways, is currently in phase II trials following well-tolerated administration in phase I studies. This narrative review aims to outline the current state of knowledge regarding the effectiveness and safety of these four biologic agents targeting IL-13 signaling.

Keywords: Atopic dermatitis; cendakimab; eblasakimab; interleukin-13; lebrikizumab; monoclonal antibody; tralokinumab.

Figure 1.

(a) Tralokinumab binds to the cytokine IL‐13 at an epitope that overlaps with the binding site of IL‐13Rα, preventing IL‐13 from binding to both IL‐13Rα1 and IL‐13Rα2 and (b) Lebrikizumab binds to IL‐13 at an epitope that overlaps with the binding site of IL‐4Rα, preventing heterodimerization of the IL‐4Rα/IL‐13Rα1 subunits. IL‐13 can still bind to IL‐13Rα2. IL-4, interleukin-4; IL-13, interleukin-13; IL-4Rα, interleukin-4 receptor α; IL-13Rα1, interleukin-13 receptor α1. The image was retrieved from an article by Gonçalves et al. This image is licensed under the Creative Commons Attribution-Non-commercial 4.0 International License. This license permits any non-commercial use, sharing, adaptation, distribution, and reproduction in any medium or format, as long as appropriate credit is given to the original author(s) and the source, and a link to the Creative Commons license is provided. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc/4.0/ (accessed 17 August 2024).

Figure 2.

a) Cendakimab binds to the cytokine IL‐13, preventing IL‐13 from binding to IL‐13Rα1 and IL‐13Rα2. b) Eblasakimab binds to IL-13Rα1, blocking IL-4 and IL-13 signaling through the type 2 receptor. This prevents IL‐13 from binding to both IL‐13Rα1 and IL‐13Rα2, and IL-4 to IL‐13Rα1. IL‐4 can still bind and signal through the type 1 receptor. IL-4, interleukin-4; IL-13, interleukin-13; IL-4Rα, interleukin-4 receptor α; IL-13Rα1, interleukin-13 receptor α1. The image was retrieved from Gonçalves et al. 2021. This image is licensed under the Creative Commons Attribution-Non-commercial 4.0 International License. This license permits any non-commercial use, sharing, adaptation, distribution, and reproduction in any medium or format, as long as appropriate credit is given to the original author(s) and the source, and a link to the Creative Commons license is provided. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc/4.0/ (accessed on 17 August 2024).