Oral Baricitinib in the Treatment of Cutaneous Lichen Planus

Author:

Hwang AngelinaORCID,Kechter JacobORCID,Do TranORCID,Hughes AlysiaORCID,Zhang Nan,Li Xing,Wasikowski RachaelORCID,Brumfiel Caitlin,Patel Meera,Boudreaux Blake,Bhullar Puneet,Nassir Shams,Yousif Miranda,DiCaudo David J,Fox Jennifer,Gharaee-Kermani Mehrnaz,Xing Xianying,Zunich Samantha,Branch Emily,Kahlenberg J. Michelle,Billi Allison C.,Plazyo Olesya,Tsoi Lam C.,Pittelkow Mark R,Gudjonsson Johann E.ORCID,Mangold Aaron RORCID

Abstract

ABSTRACTBackgroundCutaneous 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 (IFN)-γ, a cytokine implicated in the pathogenesis of LP.MethodsIn 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.ResultsAn 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 demonstrate a rapid decrease in interferon signature within 2 weeks of treatment, most prominent in the basal layer of the epidermis.ConclusionThis study demonstrates the efficacy and molecular mechanisms of JAK inhibition in LP.Trial Registration Number:NCT05188521

Publisher

Cold Spring Harbor Laboratory

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