Skin barrier function in moderate to severe AD significantly improved with dupilumab

Dupilumab has been shown to significantly improve skin barrier function factors, including transepidermal water loss, lipid composition, and filaggrin, in patients with moderate to severe atopic dermatitis.

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

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

Results from previous studies have shown that for patients with AD, transepidermal water loss (TEWL) was higher from lesions with eczema than uninvolved skin and healthy control subjects. , with more severe disease associated with higher temperature and PIE at their lesions.

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

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

They conducted the Dupilumab Skin Barrier Function Study in AD (BALISTAD), which collected TEWL and skin strip (STS) samples from lesions of 26 AD patients and 26 elderly healthy controls. from 12 to 63 years old during a 16-week course of dupilumab. .

Quantitative analysis of lipidomic and FLG degradation products was performed on STS samples collected at days 1, 15, 29, 56, and 85 and at week 16 by liquid chromatography tandem mass spectrometry.

At baseline, STS samples from AD lesions had reduced levels of FLG breakdown products, including urocanic acids (UCA) and pyroglutamic acids (PCA), compared to healthy controls (P

“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 lesions of the Alzheimer’s disease at baseline compared to healthy controls (P

With dupilumab treatment, significant increases in UCA and APC have been identified in AD skin (P P

“Partial changes in these parameters were already observed after 2 weeks, with a maximum response obtained after 8 weeks of treatment with dupilumab.”

Additionally, mean TEWL in AD lesions was shown to be significantly reduced from day 1 (47.2 g/m2 xh) at week 16 (23.6 g/m2 xh), indicating a 52% reduction (P

“Dupilumab treatment significantly improves TEWL, lipid composition and FLG in AD lesions, ensuring 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