Citations 1
TYK2 Inhibition with Deucravacitinib Improves Clinical Outcomes and Resolves Interferon-Driven Inflammation in Lichen Planopilaris
Stockard, Alyssa , Leibovit-Reiben, Zachary , Hu, Bowen , Jiang, Rundong , Roberts, Bryce T. , Penner, Scott , Li, Xing , Ramirez, Zeni , Stewart, Keegan , Fox, Jennifer , Bogle, Rachael , Zhang, Nan, Shao, Samantha C. , DiCaudo, David J. , Zunich, Samantha , Tsoi, L., Pittelkow, Mark R., Sluzevich, Jason C. , Gudjonsson, Johann E., Leibovit‐Reiben, Zachary , Zhang, Nan , Borges da Silva, Henrique , DiCaudo, David J , Zunich, Samantha , Pincelli, T , Tsoi, Lam C , Pittelkow, Mark R , Sluzevich, Jason C , Gudjonsson, Johann E , Mangold, A R , Penner, S.E., Ramirez, Z., Wasikowski, Rachael, Silva, Henrique Borges da , Pincelli, Thaís , Tsoi, Lam C. , Pittelkow, Mark R. , Mangold, Aaron R.
No container title available | March 23, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Lichen Planopilaris (LPP) is a lymphocyte-mediated scarring alopecia characterized by progressive follicular destruction and fibrosis. In this clinical trial, patients with biopsy proven LPP were treated with deucravacitinib (an oral inhibitor of tyrosine kinase 2 (TYK2)) 6 mg BID for 24 weeks (NCT-06091956). Bulk and single-cell RNA sequencing was performed on paired pre- and post-treatment scalp biopsies from baseline and week 4. Patients (N=10) demonstrated improvements in PGA (88.9%, p=0.008), LPPAI (−2.3 points, SD 1.1, p=0.002) and Skindex-16 (−21.0 points, SD 22.1, p=0.014) scores at week 24. Bulk transcriptomic analysis of untreated LPP revealed upregulation of type I Interferon (IFN)-stimulated genes and pathways related to inflammation, immune activation, keratinization, and extracellular matrix remodelling, with downregulation of immune and inflammatory pathways following treatment. Single-cell RNA-seq of LPP was characterized by enrichment of CD8+GZMK+ T cells which showed downregulation of T-cell receptor signaling as well as antiviral pathways with treatment. Basal keratinocytes exhibited reduced cytokine and interferon signaling and decreased communication with NK cells following treatment. CCL19+ fibroblasts were prominent in untreated disease was attenuated after treatment, with downregulation of type I IFN signaling. Selective TYK2 inhibition with deucravacitinib effectively suppresses these inflammatory circuits in LPP and represents a promising therapeutic strategy.