Therapeutic New Era for Atopic Dermatitis: Part 1. Biologics

Abstract

Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation and skin barrier dysfunction. We are currently experiencing a new era of understanding of the pathogenesis of AD and, as a consequence, a new era of innovation in therapeutics, including small molecules and biologic therapy. Recently, advances in translational research have challenged the traditional AD pathogenesis paradigm of AD being solely a Th2-dominant disease. Other immune pathways seem to play a role in the complex AD pathophysiology, although the clinical relevance of these additional immune pathway abnormalities is unclear. Type 1, type 22, and type 17 pathway activation (with related cytokines/chemokines) have been demonstrated in the skin and blood of AD patients. Type 2 (interleukin [IL]-4, IL-13), IL-31, and type 22 (IL-22) pathway cytokines are increased in AD acute lesions. IL-22 induces both an epidermal hyperplasia at the onset of acute AD and a marked increase in the terminal differentiation S100 genes. This understanding of pathogenesis corresponds to a historic increase in therapeutic development in AD. The extreme clinical heterogeneity and the chronic progression of AD establish the need for newer, safer, and more effective treatments, control the disease, and improve the quality of life of affected patients.

Keywords: Atopic dermatitis; Biologics; New era; Therapeutics.

Fig. 1. Mechanism of dupilumab, tralokinumab, and lebrikizumab. IL: interleukin.

Fig. 2. TSLP-OX40 axis. Keratinocyte-derived TSLP activates dendritic cells to induce the production of Th2 immunity cytokines, IL-33 appears to amplify TSLP's effect of inducing expression of OX40 ligand on dendritic cells. TSLP: thymic stromal lymphopoietin, IL: interleukin.