Dupilumab Significantly Improves Skin Barrier Function in Patients With Moderate-to-Severe Atopic Dermatitis

Hyperactivated type 2 immune responses contribute to the abnormal skin lipids in atopic dermatitis (AD). The antibody to the interleukin (IL)-4 receptor α subunit, dupilumab, blocks type 2 immune response and has been efficacious in AD treatment. This study examined the effectiveness of dupilumab therapy in the regulation of skin barrier structure and function.

The 52 participants (42% female and 80.8% white) included an experimental group (26 participants with moderate-severe AD) and a control group (26 healthy volunteers). Each group included 20 adults with a median age of 40.5 years (range 18–63) and 6 adolescents with a median age of 13.5 years (range 12–17).

The experimental group received subcutaneous dupilumab on day 1 and weeks 2, 4, 6, 8, 10, 12, and 14. The control group, matched in age and gender to the participants with AD, did not receive subcutaneous treatment. Transepidermal water loss (TEWL) and lipid content in lesional and nonlesional skin were measured over time and compared between participants with AD and matched controls.

Dupilumab treatment led to early and sustained reduction in TEWL from day 15 until week 16 in participants with AD, approaching similar levels compared with controls. Dupilumab treatment normalized skin lipid composition, including decreasing levels of ceramides with nonhydroxy fatty acids and C18-sphingosine and increasing the level of esterified omega-hydroxy fatty acid-containing ceramides (P < .0005). Dupilumab also increased the ceramide chain length in lesional and nonlesional stratum corneum of AD participants.

Dupilumab treatment reduces TEWL and increases skin ceramide chain length and long-chain fatty acid proportions, restoring the skin lipid composition and hydrophobic barrier function in individuals with moderate-to-severe AD.

In this open trial, dupilumab, an approved treatment of moderate-to-severe AD, has shown efficacy in reducing water loss, restoring lipid composition, and increasing fatty acid chain length, demonstrating associations between IL-4/IL-13 blocking and improved barrier function in adolescents with AD. Future research should explore duration of improved barrier function after discontinuation of dupilumab and the relationship with TEWL and barrier function in younger children.