Citations 1
Clinical and Molecular Effects of TYK2/JAK1 Inhibition in Dermatomyositis
Mangold, Aaron, Vleugels, Ruth Ann , Shahriari, Neda , Castillo, Rochelle , Gehlhausen, Jeffrey, Jiang, Rundong , Haemel, Anna Kaye, Fox, Jennifer Callahan, Bogle, Rachael , Roberts, Bryce T. , Penner, Scott , Li, Xing, Ramirez, Zeni , Tsoi, Alex, Shaw, Katharina, Cascino, Matthew, Johnson, BE, Kahlenberg, J. Michelle, Gudjonsson, Johann E., Paik, Julie J. , Sluzevich, Jason C. , Haemel, Anna K. , Bogle, R, Shaw, Katharina S. , Cascino, Matthew D., Kahlenberg, J. Michelle , Christopher‐Stine, Lisa , Fernandez, Anthony P , Fiorentino, David Franklin , Werth, Victoria P. , Gudjonsson, Johann E
No container title available | June 26, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Dermatomyositis is driven by overactivation of type I and II interferons and other proinflammatory cytokines that signal via the JAK-STAT pathway. We conducted a 12-week, open-label study of brepocitinib, an oral TYK2/JAK1 inhibitor, in five adults with severe cutaneous dermatomyositis. Treatment was associated with rapid, clinically meaningful improvement in cutaneous disease activity. Single-cell and spatial transcriptomic profiling of lesional skin showed marked suppression of interferon-responsive pathways and inflammatory cell states by week 4. Together with findings from a Phase 3 randomized trial in DM patients with skin and muscle involvement (VALOR, NCT05437263 ), these data support TYK2/JAK1 inhibition as a promising therapeutic strategy for DM.