The following is a summary of “Longitudinal integrated proteomic and metabolomic skin changes in atopic dermatitis patients treated with dupilumab,” published in the January 2025 issue of Allergy and Immunology by Goleva et al. 

Dupilumab inhibits IL-4/IL-13 driven inflammation, offering significant clinical benefits in atopic dermatitis (AD) treatment. 

Researchers conducted a retrospective study to assess longitudinal protein and metabolite composition in AD skin during dupilumab treatment. 

They collected skin tape strips (STS) from the lesional and non-lesional skin of 20 patients with AD and 20 healthy volunteers (HV) over 16 weeks of dupilumab treatment. STS extracts were analyzed using LC-MS proteomic and targeted metabolomic techniques. 

The results showed that approximately 2,500 proteins were identified in STS extracts, with 490 proteins present in ≥80% of AD and HV samples. Of these, 249 proteins were reduced (cluster 1), and 136 increased (cluster 2) in AD skin (both P<0.0001 compared to HV). Cluster 1 included proteins related to barrier formation, lysosomal enzymes, and oxidative response, while cluster 2 was enriched for epidermal hyperplasia markers, glycolytic enzymes, and actin filament proteins. Dupilumab treatment for 16 weeks significantly increased cluster 1 and decreased cluster 2 proteins (P<0.0001), approaching HV skin levels. Significant metabolite changes were also observed, including amino acids, nucleotide breakdown products, and antioxidants. 

Investigators established that dupilumab treatment inhibited epidermal hyperplasia significantly and improved epidermal differentiation in patients with AD. These changes correlated with clinical improvements in transepidermal water loss (TEWL) and disease severity. 

Source: jacionline.org/article/S0091-6749(25)00071-5/abstract