3D imaging elucidates neuroimmune dynamics in atopic dermatitis skin treated with ruxolitinib cream

Summary: Abstract Body: Atopic dermatitis (AD) is a chronic, inflammatory skin disease with heterogeneous lesions and a complex pathophysiology. The phase 2, open-label SCRATCH-AD study assessed the effects of 1.5% ruxolitinib (RUX) cream (selective JAK1/JAK2 inhibitor) in patients with AD. Adults (N=49) with ≤20% affected BSA applied cream twice daily for 28 days and achieved rapid, sustained itch relief and significant clinical improvement. To explore effects on the AD neuroimmune landscape, 4-mm punch biopsies were collected from lesional and nonlesional skin at baseline and from lesional sites after 28 days of treatment in a subset of 22 patients. Biopsies were stained for nuclei(TO-PRO-3), immune cells (CD45), and peripheral nerves (PGP9.5) and analyzed using Alpenglow Biosciences’ Aurora 3Di light-sheet microscope and advanced 3Dm imaging workflows. Machine learning algorithms quantified nerve volume, epidermal thickness, immune cell density, and immune-nerve spatial relationships. Nerve volume did not decrease with treatment, aligning with the observation that nerve fiber density did not differ between lesional and nonlesional skin at baseline. Treatment significantly reduced epidermal thickness and CD45+ immune cells in the epidermis and papillary dermis, with an increased distance between CD45+ cells and nerves observed only in the epidermis. These changes correlated with clinical scores (EASI, IGA). These findings confirm that RUX cream treatment may rapidly transform lesional skin to resemble nonlesional skin, with marked decreases in epidermal thickness and overall immune cell infiltration while leaving nerve fiber volume unchanged. This reinforces the observation that AD lesional and nonlesional skin share similar nerve volume characteristics. By leveraging cutting-edge 3D imaging and machine learning, this study introduces an innovative framework for understanding skin diseases. Angelina Volkova¹, Chifei Sun¹, Heather Bullins², Konstantin Popovic³, Shikhar Dhingra⁴, Nathan Grant⁴, Caleb Stoltzfus⁴, Nicholas P. Reder⁴, Cynthia Timmers², Susan H. Smith¹ 1. Incyte Corporation, Wilmington, DE, United States. 2. Incyte Research Institute, Wilmington, DE, United States. 3. Incyte Biosciences International Sarl, Morges, Switzerland. 4. Alpenglow Biosciences, Seattle, WA, United States. Clinical Research: Interventional Research