Blockade of IL-13 signaling improves skin barrier function and biology in patients with moderate to severe atopic dermatitis.

BACKGROUND: Interleukin (IL)-13 is a key driver of inflammation and barrier dysfunction in atopic dermatitis (AD). While there is robust evidence that tralokinumab, a monoclonal antibody neutralizing IL-13, reduces inflammation and clinical disease activity, less is known about its effects on barrier function.

OBJECTIVES: To characterize effects of tralokinumab treatment on skin barrier function.

METHODS: Transepidermal water loss (TEWL), stratum corneum hydration (SCH), natural moisturizing factor (NMF) content, histopathological characteristics, biomarker expression and microbiome composition were evaluated in lesional, non-lesional, and sodium lauryl sulfate (SLS)-irritated skin of 16 AD patients over the course of 16 weeks of tralokinumab treatment.

RESULTS: All clinical severity scores decreased significantly over time. At week 16, mean TEWL in target lesions decreased by 32.66% (p = 0.01), and SCH increased by 58.44% (p = 0.004), along with histological reduction in spongiosis (p = 0.003), keratin 16 expression and epidermal thickness (p = 0.001). In parallel, there was a significant decrease in several barrier dysfunction-associated and pro-inflammatory proteins such as fibronectin (p = 0.006), CCL17/TARC (p = 0.025) and IL-8 (p = 0.014), with significant changes already at week 8. Total bacterial load and Staphylococcus aureus abundance were significantly reduced from week 2.

CONCLUSION: Tralokinumab treatment improves skin physiology, epidermal pathology, and dysbiosis, further highlighting the pleiotropic role of IL-13 in AD pathogenesis.