Rapid response of lichen planus to baricitinib associated with suppression of cytotoxic CXCL13+CD8+ T cells
Angelina S. Hwang, Jacob A. Kechter, Tran H. Do, Alysia N. Hughes, Nan Zhang, Xing Li, Rachael Bogle, Caitlin M. Brumfiel, Meera H. Patel, Blake Boudreaux, Puneet Bhullar, Shams Nassir, Miranda L. Yousif, Alyssa L. Stockard, Zachary Leibovit-Reiben, Ewoma Ogbaudu, David J. DiCaudo, Jennifer Fox, Mehrnaz Gharaee-Kermani, Xianying Xing, Samantha Zunich, Emily Branch, J. Michelle Kahlenberg, Allison C. Billi, Olesya Plazyo, Lam C. Tsoi, Mark R. Pittelkow, Johann E. Gudjonsson, Aaron R. Mangold
Angelina S. Hwang, Jacob A. Kechter, Tran H. Do, Alysia N. Hughes, Nan Zhang, Xing Li, Rachael Bogle, Caitlin M. Brumfiel, Meera H. Patel, Blake Boudreaux, Puneet Bhullar, Shams Nassir, Miranda L. Yousif, Alyssa L. Stockard, Zachary Leibovit-Reiben, Ewoma Ogbaudu, David J. DiCaudo, Jennifer Fox, Mehrnaz Gharaee-Kermani, Xianying Xing, Samantha Zunich, Emily Branch, J. Michelle Kahlenberg, Allison C. Billi, Olesya Plazyo, Lam C. Tsoi, Mark R. Pittelkow, Johann E. Gudjonsson, Aaron R. Mangold
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Clinical Research and Public Health Dermatology

Rapid response of lichen planus to baricitinib associated with suppression of cytotoxic CXCL13+CD8+ T cells

Abstract

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 NCT05188521FUNDING Eli Lilly, Appignani Benefactor Funds, 5P30AR075043, Mayo Clinic Clinical Trials Stimulus Funds.

Authors

Angelina S. Hwang, Jacob A. Kechter, Tran H. Do, Alysia N. Hughes, Nan Zhang, Xing Li, Rachael Bogle, Caitlin M. Brumfiel, Meera H. Patel, Blake Boudreaux, Puneet Bhullar, Shams Nassir, Miranda L. Yousif, Alyssa L. Stockard, Zachary Leibovit-Reiben, Ewoma Ogbaudu, David J. DiCaudo, Jennifer Fox, Mehrnaz Gharaee-Kermani, Xianying Xing, Samantha Zunich, Emily Branch, J. Michelle Kahlenberg, Allison C. Billi, Olesya Plazyo, Lam C. Tsoi, Mark R. Pittelkow, Johann E. Gudjonsson, Aaron R. Mangold

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Figure 2

LP is an IFN-driven disease process.

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LP is an IFN-driven disease process. (A) Volcano plot of bulk RNA-Seq da...
(A) Volcano plot of bulk RNA-Seq data comparing lesional versus nonlesional LP skin at day 0 (n = 10 and 9, respectively) (red color shows FDR < 0.05 and log2 FC > 1 or less than negative 1, blue is FC < 1 and less than negative 1 and FDR < 0.05), green is FC > 1 or less than negative 1)and FDR > 0.05). (B) Enriched GO categories in DEGs between lesional versus nonlesional LP skin (red and blue colors represent enriched GO categories among increased versus decreased DEGs, respectively, P < 0.05). (C) Cellular deconvolution of fibroblasts, KCs, myeloid cells, and T cells on the Visium 10X spatial expression platform (representative of n = 9). (D) IHC of the T cell marker CD3, pSTAT2, IFN-γ, and CXCL9 (representative of n = 9). Scale bar: 100 μm.