Tralokinumab Treatment of Atopic Dermatitis Induces a Progressive Transcriptomic Response

Atopic dermatitis is characterized by a complex epidermal barrier deficiency and exaggerated immune responses dominated by type 2 mechanisms with variable contributions of additional immune axes. IL-13 is overexpressed in atopic dermatitis skin and a key driver of both barrier dysfunction and inflammation. In this study, we prospectively studied the effects of IL-13 inhibition with tralokinumab on cutaneous transcriptome profiles using RNA sequencing of biopsies from 16 patients with moderate-to-severe atopic dermatitis obtained at baseline, week 2, and week 16. Tralokinumab therapy induced early and delayed expression changes and progressively shifted the transcriptomic profile of lesional toward nonlesional skin by modulating both genes associated with keratinocyte proliferation and differentiation, itch signaling, and downstream inflammatory responses. At week 16, 751 genes were still significantly dysregulated compared with those in healthy control skin, reinforcing the need for long-term immunomodulatory therapy of moderate-to-severe atopic dermatitis to achieve deep responses. The study was registered with ClinicalTrials.gov (NCT04556461).