Tralokinumab treatment of Atopic dermatitis induces a progressive transcriptomic response

Atopic dermatitis (AD) is characterized by a complex epidermal barrier deficiency and exaggerated immune responses dominated by type-2-mechanisms with variable contributions of additional immune axes. Interleukin (IL)-13 is overexpressed in AD skin and a key driver of both barrier dysfunction and inflammation. We here prospectively studied the effects of IL-13 inhibition with tralokinumab on cutaneous transcriptome profiles using RNA sequencing of biopsies from 16 moderate-to-severe AD patients obtained at baseline, week 2 and week 16. Tralokinumab therapy induced early and delayed expression changes, and progressively shifted the transcriptomic profile of lesional towards non-lesional 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 as compared to healthy control skin, reinforcing the need for long-term immunomodulatory therapy of moderate to severe AD to achieve deep responses. The study was registered with ClinicalTrials.gov (NCT04556461)