Tralokinumab modulates the transcriptomic profile of lesional and non-lesional skin in adolescents with moderate-to-severe atopic dermatitis assessed by tape-stripping

Background: Skin tape strips are increasingly being utilized as a minimally-invasive alternative to biopsies to assess skin biomarkers in patients with atopic dermatitis (AD). Tralokinumab is a high-affinity, monoclonal antibody that neutralizes interleukin (IL)-13. Here, we evaluated the effect of tralokinumab on gene expression in lesional and non-lesional skin of adolescents with moderate-to-severe AD in the Phase 3 ECZTRA 6 trial (NCT03526861). Adolescents (age 12-17) were randomized to subcutaneous tralokinumab 150mg or 300mg every 2 weeks, or placebo. We collected tape strips from 78 patients for transcriptomic analysis by RNA-Seq. Greater proportions of patients receiving tralokinumab achieved the primary endpoints of IGA 0/1 (150mg/300mg 21.4%/17.5% vs placebo 4.3%; P<0.001/P=0.002) and EASI- 75 (28.6%/27.8% vs 6.4%; P<0.001/P<0.001) at Week 16. At baseline, 2575 genes were differentially expressed between lesional and non-lesional skin, including genes that regulate inflammation and barrier integrity. Between baseline and Week 16, tralokinumab 300 mg induced improvement in the skin gene signature, defined as a shift from lesional towards non-lesional profile, in 41% of the differentially expressed genes in lesional skin. Tralokinumab 150 mg led to 29% improvement in gene expression compared to 4% improvement with placebo. Tralokinumab treatment modulated the expression of key AD markers including C-C motif chemokine ligand 13 (CCL13), IL-20, IL-24, and barrier markers such as FLG, S100A12, and CAMP. This study demonstrates that IL-13 neutralization with tralokinumab modulates transcription of key AD genes in lesional and non-lesional skin of adolescents with AD and supports the utility of tape-stripping for assessing skin biomarker profiles in AD.