Department of Dermatology.
Department of Biostatistics.
JCI Insight. 2016 Sep 22;1(15):e89790. doi: 10.1172/jci.insight.89790.
Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of 1.7%; there are no FDA-approved treatments for AA. We previously identified a dominant IFN-γ transcriptional signature in cytotoxic T lymphocytes (CTLs) in human and mouse AA skin and showed that treatment with JAK inhibitors induced durable hair regrowth in mice by targeting this pathway. Here, we investigated the use of the oral JAK1/2 inhibitor ruxolitinib in the treatment of patients with moderate-to-severe AA. We initiated an open-label clinical trial of 12 patients with moderate-to-severe AA, using oral ruxolitinib, 20 mg twice per day, for 3-6 months of treatment followed by 3 months follow-up off drug. The primary endpoint was the proportion of subjects with 50% or greater hair regrowth from baseline to end of treatment. Nine of twelve patients (75%) demonstrated a remarkable response to treatment, with average hair regrowth of 92% at the end of treatment. Safety parameters remained largely within normal limits, and no serious adverse effects were reported. Gene expression profiling revealed treatment-related downregulation of inflammatory markers, including signatures for CTLs and IFN response genes and upregulation of hair-specific markers. In this pilot study, 9 of 12 patients (75%) treated with ruxolitinib showed significant scalp hair regrowth and improvement of AA. Larger randomized controlled trials are needed to further assess the safety and efficacy of ruxolitinib in the treatment of AA. Clinicaltrials.gov NCT01950780. Locks of Love Foundation, the Alopecia Areata Initiative, NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the Irving Institute for Clinical and Translational Research/Columbia University Medical Center Clinical and Translational Science Award (CUMC CTSA).
斑秃（AA）是一种常见的自身免疫性疾病，终生风险为 1.7%；目前尚无 FDA 批准的 AA 治疗方法。我们之前在人类和小鼠 AA 皮肤的细胞毒性 T 淋巴细胞（CTL）中鉴定出一个占优势的 IFN-γ转录特征，并表明通过靶向该途径，使用 JAK 抑制剂治疗可在小鼠中诱导持久的毛发再生。在这里，我们研究了口服 JAK1/2 抑制剂芦可替尼治疗中重度 AA 患者的用途。我们启动了一项针对 12 名中重度 AA 患者的开放性临床试验，使用口服芦可替尼，每天两次，每次 20mg，治疗 3-6 个月，然后停药 3 个月。主要终点是从基线到治疗结束时，毛发再生达到 50%或以上的受试者比例。12 名患者中的 9 名（75%）对治疗有显著反应，治疗结束时平均毛发再生 92%。安全参数基本在正常范围内，未报告严重不良事件。基因表达谱分析显示，治疗相关的炎症标志物下调，包括 CTL 和 IFN 反应基因的特征以及毛发特异性标志物的上调。在这项初步研究中，12 名患者中有 9 名（75%）接受芦可替尼治疗后头皮毛发明显再生，AA 得到改善。需要更大规模的随机对照试验来进一步评估芦可替尼治疗 AA 的安全性和有效性。Clinicaltrials.gov NCT01950780。Locks of Love 基金会、斑秃倡议、NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases（NIAMS）和 Irving 研究所临床和转化研究/哥伦比亚大学医学中心临床和转化科学奖（CUMC CTSA）。
