Citations 2
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.
Rapid response of lichen planus to baricitinib associated with suppression of cytotoxic CXCL13+CD8+ T cells
Kechter, Jacob , Do, Tran , Hughes, Alysia N., Zhang, Nan , Bogle, Rachael , Brumfiel, Caitlin M. , Boudreaux, Blake , Bhullar, Puneet , Nassir, Shams , Yousif, Miranda , Stockard, Alyssa , Leibovit-Reiben, Zachary , Ogbaudu, Ewoma , DiCaudo, David J. , Fox, Jennifer, Xing, Xianying , Zunich, Samantha , Branch, Emily, Billi, Allison C. , Pittelkow, Mark R. , Mangold, Aaron R. , Stockard, Alyssa , Hwang, Angelina S , Kechter, Jacob A, Patel, Meera H. , Yousif, Miranda L, Stockard, Alyssa L, Fox, Jennifer , Mangold, A R , Billi, Allison C , Hwang, Angelina , Li, Xing , Wasikowski, Rachael, Patel, Meera , Leibovit‐Reiben, Zachary , Gharaee‐Kermani, Mehrnaz , Kahlenberg, J. Michelle , Plazyo, Olesya , Tsoi, Lam C. , Gudjonsson, Johann E
Journal of Clinical Investigation | November 14, 2024 | Volume: 135 | Issue: 2 | Pages: No page available
BACKGROUND Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of IFN-γ, a cytokine implicated in the pathogenesis of LP. METHODS In this phase II trial, 12 patients with cutaneous LP received 2 mg daily baricitinib for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre- and posttreatment samples. RESULTS An early and sustained clinical response was seen, with 83.3% of patients responsive at week 16. Our molecular data identified a unique, oligoclonal IFN-γ, CD8 + , and CXCL13 + cytotoxic T cell population in LP skin and demonstrated a rapid decrease in IFN signature within 2 weeks of treatment, most prominently in the basal layer of the epidermis. CONCLUSION This study demonstrates the efficacy and molecular mechanisms of JAK inhibition in LP. TRIAL REGISTRATION NCT05188521 FUNDING Eli Lilly, Appignani Benefactor Funds, 5P30AR075043, Mayo Clinic Clinical Trials Stimulus Funds.