775 - Dupilumab Treatment Normalizes Skin Barrier Structure and Function and Improves Clinical Outcomes in Patients with Atopic Dermatitis

Type 2 inflammatory cytokines IL-4 and IL-13 contribute to skin barrier disruption in atopic dermatitis (AD).

Objective:

We evaluated the effect of dupilumab on skin barrier function, lipid composition, and clinical outcomes in adults and adolescents with moderate-to-severe AD.

Design/Methods:

BALISTAD (NCT04447417) was a 16-week, open-label study. Transepidermal water loss (TEWL) after skin tape stripping (STS) was assessed in lesional skin of 26 AD patients treated with dupilumab and on the skin of 26 healthy volunteers. Lipid composition was assessed by liquid chromatography tandem mass spectrometry.

Results:

Median TEWL after 5 STS in AD lesions was significantly reduced from baseline starting at Week 2 (P < 0.0001) and sustained through Week 16 (P < 0.0001). At Week 16, there was no difference in the LS mean TEWL in lesional skin of AD patients vs healthy volunteers’ skin (P = 0.225).

At baseline, the ratio of total C20 EOS ceramides to total C20 NS ceramides in AD lesional skin was significantly lower than in skin of healthy volunteers (P = 0.003). At Week 16, the ratio significantly improved in AD lesional skin, showing no difference compared with skin of healthy volunteers' (P = 0.2118).

Clinical assessments of AD lesions, itch, sleep, and quality of life significantly improved from baseline (P < 0.0001). Overall safety was consistent with the known dupilumab safety profile.

Conclusion(s): Dupilumab treatment normalizes skin barrier function in patients with moderate-to-severe AD and is associated with significant improvement in AD signs and symptoms, and quality of life.