1558 Global proteomic evaluation reveals longitudinal molecular skin improvements in atopic dermatitis patients treated with dupilumab

Dupilumab, a monoclonal antibody that targets IL-4Ra, has shown significant clinical benefits in modulation of type 2(T2) inflammation in atopic dermatitis(AD). To date, there are no detailed proteomic studies of longitudinal changes in AD skin proteins in patients treated with dupilumab. Assessments of lesional and non-lesional skin of 20 AD patients during 16 weeks of dupilumab treatment were done by skin tape stripping(STS) and compared to STS of 20 healthy volunteers (HV). STS protein extracts were examined at baseline, weeks 8 and 16 of treatment by liquid chromatography mass spectrometry proteomic analysis. 490 proteins were detected in ≥80% of AD and HV skin samples. 139 proteins were differentially expressed between AD and HV at baseline and significantly changed during dupilumab treatment (p<0.05). At baseline, expression of 49 proteins, including proteins involved in epidermal barrier formation (KRT2, KRT77, TGM3, CDSN, DSC3, KLK7, BLMH), lysosomal enzymes required for lamellae assembly (ASAH1, GLB1, HEXA, HEXB, GAA, FUCA1, ALOXE3), oxidative response enzymes (CAT, GSS, GGCT) and proteasome subunits, was significantly lower in AD skin compared to HV (p<0.0001). Expression of these proteins in AD skin significantly increased at weeks 8 and 16 of dupilumab treatment (both p<001) and approached levels observed in HV. Longitudinal assessment of the skin proteome in AD patients treated with dupilumab demonstrated significant improvement in the expression of proteins involved in epidermal differentiation, normalization of lamellae assembly and antioxidant defense by 16 weeks of treatment, suggesting that these proteins are under control of T2 cytokines in AD skin.