Dupilumab Improves Clinical and Immunologic Markers in NS

Key Takeaways

• Dupilumab was linked with clinical and immunologic improvements in patients with Netherton syndrome (NS).

• Treatment with dupilumab normalized cutaneous immune cell profiles and barrier protein expression.

Results from a recent pilot study suggest an IL-4/IL-13 blockade with dupilumab significantly improved skin and immunologic abnormalities in patients with Netherton syndrome (NS).

Researchers on the study compared chemokine and cytokine profiles among patients with NS, atopic dermatitis (AD), and controls. While Th2 chemokines such as CCL11, CCL17, CCL18, and CCL26 were elevated in both NS and AD, unique immunologic features distinguished NS, including higher IL-9 and IL-18 levels and reduced epidermal thymic stromal lymphopoietin (TSLP). NS skin exhibited architectural abnormalities such as acanthosis, stratum corneum detachment, and decreased FLG, CDSN, and DSG1 expression.

Dupilumab therapy resulted in visible clinical improvement by week 8, sustained for up to 30 months without serious adverse events. Dupilumab reduced serum IgE, CCL17, CCL26, IFN-γ, and IL-18 levels. Efficacy was further supported by the restoration of epidermal barrier proteins and normalization of T cell and Langerhans cell distributions. The expression of the protease inhibitor WFDC12 increased with treatment.

“These data highlight Th2-skewed immunity in NS and emphasise the amelioration of NS features through dupilumab treatment,” the authors wrote.

Source: Blunder S, et al. Experimental Dermatology. 2025. doi:10.1111/exd.70113