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

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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.

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