Skin Barrier Function in Moderate to Severe AD Significantly Improved With Dupilumab

Skin barrier function was shown to be significantly improved with dupilumab treatment among adult and adolescent patients with atopic dermatitis (AD). Findings were reported at the 2022 American Academy of Allergy, Asthma & Immunology Annual Meeting and are published in The Journal of Allergy and Clinical Immunology.

Characterized by abnormal skin lipid and filaggrin (FLG) content, AD development has been linked with skin barrier function, which protects against water loss and numerous external stressors.

Prior study findings have shown that for patients with AD, transepidermal water loss (TEWL) was higher at lesions showing eczema than uninvolved skin and that of healthy control subjects, with more severe disease associated with a higher temperature and TEWL at their lesions.

Although treatment with moisturizers has been shown to improve skin barrier function in the initial phase of AD, progression to more advanced disease has required effective topical and systemic therapies to reduce immune pathway activation and general inflammation.

Dupilumab, a human monoclonal antibody against the interleukin (IL)-4 receptor α-subunit (IL-4Rα) that inhibits IL-4 and IL-13 signaling, has previously demonstrated significant efficacy and an acceptable safety profile in moderate to severe AD, but researchers of the present study note that its role in the regulation of skin barrier has not been fully evaluated.

They conducted the dupilumab skin barrier function study in AD (BALISTAD), which collected TEWL and skin tape strip (STS) samples from lesions of 26 patients with AD and 26 healthy controls aged 12 to 63 years over a 16-week course of dupilumab treatment.

A quantitative lipidomic and FLG breakdown product analysis was performed on STS samples collected at days 1, 15, 29, 56, and 85 and week 16 via liquid chromatography tandem mass spectrometry.

At baseline, STS samples from AD lesions exhibited reduced levels of FLG breakdown products, including urocanic acids (UCA) and pyroglutamic acids (PCA), vs healthy controls (P < .05).

“Significantly increased levels of non-hydroxy fatty acid sphingosine ceramides (NS-CER) and decreased levels of esterified omega-hydroxy fatty acid sphingosine ceramides (EOS-CER) were found in AD lesions at baseline vs healthy controls (P < .05),” reported the study authors.

With dupilumab treatment, significant increases in UCA and PCA were identified in skin with AD (P < .05); a significant decrease in NS-CER and increase in EOS-CER were also found in AD (P < 0.05). This resulted in the normalization of the NS-CER/EOS-CER ratio following treatment.

“Partial changes for these parameters were already observed after 2-weeks, with a maximal response achieved after 8 weeks of dupilumab treatment.”

Furthermore, mean TEWL in AD lesions was shown to be significantly reduced from day 1 (47.2 g/m² x h) to week 16 (23.6 g/m² x h), indicating a 52% reduction (P < .0001).

“Dupilumab treatment significantly improves TEWL, lipid composition, and FLG in AD lesions, providing normalization of epidermal barrier function.”

Reference

Berdyshev E, Goleva E, Bissonnette R, et al. Dupilumab treatment significantly improves skin barrier function in adult and adolescent patients with moderate to severe atopic dermatitis. J Allergy Clin Immunol. Published online February 1, 2022. doi:10.1016/j.jaci.2021.12.073