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.

中文翻译：

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扁平苔藓对巴瑞替尼的快速反应与抑制细胞毒性 CXCL13 + CD8 + T 细胞相关。


背景 皮肤扁平苔藓 （LP） 是一种顽固性、难以治疗的炎症性皮肤病，其特征是皮肤上出现瘙痒、平顶、紫罗兰色丘疹。Baricitinib 是一种口服 Janus 激酶 （JAK） 1/2 抑制剂，可阻断干扰素 γ （IFN）-γ 的信号通路，干扰素 γ （IFN）- 是一种与 LP 发病机制有关的细胞因子。方法 在这项 II 期试验中，12 名皮肤 LP 患者接受巴瑞替尼每天 2 mg 治疗，持续 16 周，同时对治疗前后样本进行深入的空间、单细胞和大量转录组学分析。结果 观察到早期和持续的临床反应，83.3% 的患者在第 16 周有反应。我们的分子数据在 LP 皮肤中鉴定出一种独特的寡克隆 IFN-γ、CD8+、CXCL13+ 细胞毒性 T 细胞群，并表明 IFN 特征在治疗后 2 周内迅速下降，最突出的是表皮的基底层。结论 本研究证明了 JAK 抑制在 LP 中的疗效和分子机制。试验注册 NCT05188521。资金来源的作用。Eli Lilly，Appignani 捐助基金，5P30AR075043，梅奥诊所临床试验刺激基金。