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Clinical MedicineIn-Press PreviewDermatology Open Access | 10.1172/JCI179436

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

Angelina S. Hwang,1 Jacob A. Kechter,1 Tran H. Do,2 Alysia N. Hughes,1 Nan Zhang,3 Xing Li,1 Rachael Bogle,2 Caitlin M. Brumfiel,1 Meera H. Patel,1 Blake Boudreaux,1 Puneet Bhullar,1 Shams Nassir,1 Miranda L. Yousif,1 Alyssa L. Stockard,1 Zachary Leibovit-Reiben,1 Ewoma Ogbaudu,1 David J. DiCaudo,1 Jennifer Fox,2 Mehrnaz Gharaee-Kermani,2 Xianying Xing,2 Samantha Zunich,1 Emily Branch,1 J. Michelle Kahlenberg,2 Allison C. Billi,2 Olesya Plazyo,2 Lam C. Tsoi,2 Mark R. Pittelkow,1 Johann E. Gudjonsson,2 and Aaron R. Mangold1

1Department of Dermatology, Mayo Clinic Arizona, Scottsdale, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Quantitative Health Sciences, Mayo Clinic Arizona, Scottsdale, United States of America

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1Department of Dermatology, Mayo Clinic Arizona, Scottsdale, United States of America

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2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

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2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

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2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

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2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

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Published November 14, 2024 - More info

J Clin Invest. https://doi.org/10.1172/JCI179436.
Copyright © 2024, Hwang et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published November 14, 2024 - Version history
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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 interferon gamma (IFN)-γ, a cytokine implicated in the pathogenesis of LP.

METHODS. In this phase II trial, twelve patients with cutaneous LP received baricitinib 2 mg daily for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre- and post-treatment 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+, 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.

ROLE OF FUNDING SOURCE. Eli Lilly, Appignani Benefactor Funds, 5P30AR075043, Mayo Clinic Clinical Trials Stimulus Funds.

Supplemental material

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View Supplemental Table 5. DEGs in lesional LP vs non-lesional skin. This large table has been uploaded as a separate spreadsheet.

Version history
  • Version 1 (November 14, 2024): In-Press Preview
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