Topical ruxolitinib 1.5% cream improves immune and barrier dysregulation in patients with moderate-to-severe seborrheic dermatitis

Summary: Abstract Body: Seborrheic dermatitis (SD) is a chronic inflammatory skin disease with limited treatment options that presents with scaly, pruritic lesions across the face, scalp, upper trunk, and skinfolds. This open-label trial aimed to assess both the clinical and molecular effects of 4 weeks topical ruxolitinib treatment in SD using tape-stripping, a minimally invasive skin sampling technique. 25 adult patients with moderate-to-severe SD (Investigator’s Global Assessment/IGA 3-4) were treated twice daily with ruxolitinib 1.5% cream. Tape-strips were collected from lesional/LS and non-lesional/NL facial skin at baseline, LS after 4 weeks of treatment, and normal facial skin of 20 healthy controls. 20/25 patients achieved IGA 0/1 at week 4. 3939 DEGs/differentially expressed genes (1945 up/1994 down) at baseline between LS and normal skin and 1990 DEGs (1000 up/990 down) between LS and NL skin were evaluated using RNA-seq (fold change/FCH>2 and false discovery rate/FDR<0.05). Ruxolitinib normalized the LS transcriptome towards NL and normal skin, with 82% and 53% respective improvements at week 4. With treatment, there was significantly decreased expression of Th17-related (IL17A/F, IL23A, IL36G, PI3, CAMP/LL-37, STAT3) and Th22-related (i.e. IL22, SERPINB1/4, S100A7A/8/9/12) pathways. Moderate Th1 downregulation (OASL, MX1, STAT1, IL1B) and upregulation of barrier markers (FA2H, ELOVL3/5, CLDN1) markers was also observed (FDR<0.05 for all). These results demonstrate meaningful normalization of the transcriptome in patients with moderate-to-severe SD, supporting the addition of ruxolitinib to the treatment armamentarium. The observed improvement identifies a strafication of complete responders in 4 weeks, suggesting a molecular propensity for treatment response to be further investigated. Meredith Manson¹, Benjamin Ungar¹, Madeline Kim¹, Mark Taliercio¹, Anusha Pasumarthi¹, Marguerite Meariman¹, Xinyi Lin¹, Digpal Gour¹, Panipak Temboonnark¹, Ragasruti Metukuru¹, Joel Correa da Rosa¹, Yeriel Estrada¹, Emma Guttman-Yassky¹ 1. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Clinical Research: Interventional Research