33557 Dupilumab treatment restores skin barrier function and improves clinical and patient reported outcomes in adults and adolescents with moderate to severe atopic dermatitis

Abstract

Objective: To determine the effect of dupilumab on skin barrier function in adults and adolescents with moderate to severe atopic dermatitis (AD). Methods: Transepidermal water loss (TEWL) was measured before and after skin tape stripping (STS) in AD lesional skin (n = 26) over 16 weeks of dupilumab therapy, and matched healthy control skin (n = 26) in an Open Label Exploratory study (BALISTAD [NCT04447417]). TEWL before and after STS was assessed repeatedly between baseline and Week 16. Change from baseline in TEWL was analyzed using a mixed model, adjusting for age, gender, and lesion location. Secondary and exploratory endpoints included clinical, and patient reported outcomes. Photographic documentation was also obtained during the study. Results: The mean TEWL in AD lesions was significantly reduced from baseline, (both before STS and following 5/10/15/20 STS) ranging from 47.2, 62.5, 73.0, 80.4, and 88.0 g/m2 x h at baseline to 23.6, 28.3, 34.3, 42.9, and 49.2 g/m2 x h at Week 16, respectively; representing 48% to 57% reduction (P < .0001). By week 16, the mean distribution of TEWL in AD patients was close to matched healthy controls. Clinical and patient reported outcomes (EASI, SCORAD, peak pruritus NRS, sleep quality NRS, POEM and DLQI/CDLQI) significantly improved from baseline (P < .0001 for all endpoints except CDLQI [P < .01]). Conclusions: Dupilumab treatment leads to significant improvement in TEWL in AD lesional skin, demonstrating restoration of epidermal barrier function and improvement in signs and symptoms of AD.