666 Effect of Dupilumab on the Host-Microbe Interface in Atopic Dermatitis

Atopic dermatitis (AD) is characterized by Staphylococcus aureus (SA) colonization, epithelial defects & type 2 immunity. Dupilumab (DPL), which blocks the biological actions of IL-4 & -13, provides an opportunity to probe the import of type 2 inflammation on microbial, epithelial & immune features of AD. To do this, the Atopic Dermatitis Research Network designed a 6wk, RDBPC trial with high density sampling (Days 0, 3, 7, 14, 21, 28 & 42) to quantify these changes & assess how they relate to disease severity (EASI, NRS, IGA & SCORAD). Seventy-two, moderate-severe adult AD subjects were assigned 2:1 to DPL vs placebo. The primary endpoint was SA abundance (qPCR) on lesional skin at 28 days. Secondary endpoints were: 1) SA abundance on lesional (L) skin at remaining timepoints & nonlesional (NL) skin at all timepoints, 2) skin barrier function (Transepidermal Water Loss before & after tape-strips) and 3) EASI, IGA, SCORAD & NRS. Exploratory endpoints are: 1) composition & abundance of bacterial taxa at NL & L skin, 2) skin biopsy transcriptome (NL & L skin), 3) lipidomics (NL & L skin), 4) expression of SA virulence factors (NL & L skin), 5) confocal imaging of tight junctions & SA (NL skin only), 6) PBMC immunoprofiling & 7) serum biomarkers. Mechanistic readouts are anticipated by Q2 2021. By integrating this multi-scale, high density data, we will model the complex interactions between the host and microbiome with and without type 2 blockade.