Novel topical and systemic therapies in atopic dermatitis

Abstract

Atopic dermatitis (AD) is the most common inflammatory skin disease driven by both terminal keratinocyte differentiation defects and type 2 immune responses, and this condition causes psychological and social morbidity. Although patients with severe AD require systemic immunotherapy, conventional agents including ciclosporin could not be used for several years due to side effects such as nephrotoxicity, hypertension and long-term risks of malignancy. It is well known that dupilumab, which blocks receptor binding of both IL-4 and IL-13, is remarkably efficacious in the treatment of AD. We have entered a new era when many novel topical and systemic agents that may have great potential in AD treatment are emerging through clinical trials. The purpose of this article is to summarize the efficacy and safety of the current topical and systemic therapies in AD by reviewing recently published papers regarding phase II/III clinical trials. It is revealed that topical phosphodiesterase 4 inhibitors and Janus kinase (JAK) inhibitors are promising treatments for AD. Moreover, systemic therapies such as biologics targeting IL-13 and oral JAK inhibitors show strong efficacy in AD.

IL‐13 modulates ∆Np63 levels causing altered expression of barrier‐ and inflammation‐related molecules in human keratinocytes: A possible explanation for chronicity of atopic dermatitis

“…We have shown that IL‐4/IL‐13 interferes with this process. This has been also shown in a recent study by Brauweiler et al 30 Given that recent studies have revealed that aberrant keratinocyte differentiation underlies the pathophysiology of AD, 28 , 29 the IL‐13–ΔNp63 axis would have an important role in the dysregulated keratinocyte phenotype in AD. We observed that IL‐13 stimulation for 24 h at any stage of differentiation (pre‐differentiated, differentiating, and differentiated stages) slightly upregulated the ΔNp63 gene expression level.…”

“…A growing body of studies have demonstrated that abundant IL‐13, a representative cytokine constituting type 2 inflammatory environment, derived from ILC2 or Th2 plays a pivotal role in the pathogenesis of AD 27 . On the contrary, accumulating evidence has demonstrated disturbed keratinocyte differentiation in AD 28,29 . Therefore, we investigated how IL‐13 affects ΔNp63‐mediated keratinocyte differentiation.…”

“… 27 On the contrary, accumulating evidence has demonstrated disturbed keratinocyte differentiation in AD. 28 , 29 Therefore, we investigated how IL‐13 affects ΔNp63‐mediated keratinocyte differentiation. We treated NHEKs with IL‐13.…”

Practical Recommendations for the Topical Treatment of Atopic Dermatitis in South and East Asia

“…There have been many novel developments for the treatment of moderate-to-severe AD (e.g., biologics, such as dupilumab, and small molecules, including Janus kinase inhibitors and aryl hydrocarbon receptor-modifying agents) [97,98].…”

Biologika-Therapie der atopischen Dermatitis

“…Eine erste randomisierte, doppelblinde, placebokontrollierte Phase-1-Studie zeigte vielversprechende Ergebnisse [28]: 25 Patienten erhielten insgesamt 4 Infusionen mit MOR106 oder Placebo im Abstand von einer Woche, gefolgt von einer Nachbeobachtungsphase von 10 Wo-chen. Es zeigten sich signifikante Unterschiede zwischen den beiden Gruppen, 83 % der Patienten mit der Maximaldosis erreichten einen EASI-50 nach 4 Wochen [28]. Weitere Studien werden benötigt, um diese Ergebnisse zu bestätigen.…”