Study of Anti-Malarials in Incomplete Lupus Erythematosus (SMILE)

项目摘要/摘要 系统性红斑狼疮(SLE)在相对年轻的患者中会导致主要器官损害和寿命缩短 人。早期诊断和治疗是改善SLE患者预后的关键。然而， 早期治疗干预的循证方法和适当的目标人群 干预措施不可用。我们认为抗核抗体阳性的个体 (ANA)，并表现出用于SLE分类的其他一些特征，是患SLE的高危人群 进展到这种疾病的完全全身性形式。这些人，他们的ANA水平很高 红斑狼疮分类标准中有1到2个额外的项目，被认为是不完全狼疮 红斑狼疮或Ile。我们建议用羟基氯喹(HCQ)治疗ILE患者。 不完全性红斑狼疮中的疟疾“或微笑试验。主要目标是确定是否 HCQ治疗可以防止获得定义SLE的额外临床和免疫学特征。 主要的次要目标是确定HCQ治疗是否：(1)减少狼疮疾病的活动性 以标准评分指数衡量；(2)改善患者报告的结果(3)防止积累 免疫异常，包括自身抗体和细胞因子；(4)具有可接受的毒性特征。 这项建议的具体目标是： 1.在患者中进行HCQ与安慰剂对照的双盲、安慰剂对照、多中心随机试验 和伊莱在一起。这项研究验证了这样的假设，即早期使用HCQ可以改变疾病特征，从而 导致SLE分类的异常堆积可以显著减慢。 2.确定HCQ对ILE患者疾病活动性和患者报告预后的影响。 3.研究ILE患者HCQ的免疫学特征。自身抗体、细胞因子和 趋化因子将在多路阵列上进行测量，以深入了解潜在的机制。 4.定量评价盐酸异烟肼治疗的ILE患者眼部毒性反应的发生率。全部登记在册 患者在学习治疗前后将进行标准化的眼科检查。 将制定在这一患者群体中使用和监测的建议。 SMILE试验将决定是否应该给ILE患者服用HCQ，这将为 适当的目标人群，并将提出候选生物标志物来指导治疗决定。而当 微笑不是Precision Medicine Initiative®的一部分，它与其目标是一致的。这将是迈向 测试系统性红斑狼疮疾病预防研究的可行性，并将在 将提供给狼疮研究社区用于进一步深入机制研究的资源库。

Project Summary/Abstract Systemic lupus erythematosus (SLE) causes major organ damage and shortens lifespan in relatively young persons. Early diagnosis and treatment are essential to improving outcomes for SLE patients. However, evidenced-based approaches to early treatment interventions and the appropriate target population for these interventions are not available. We propose that individuals who have positivity for antinuclear antibodies (ANAs) and who also exhibit some of the other features that are used to classify SLE, are at high risk of progressing to the full systemic form of this disease. These individuals, who have significant levels of ANA with 1 or 2 additional items from the lupus classification criteria, are considered to have incomplete lupus erythematosus or ILE. We propose to treat ILE patients with hydroxychloroquine (HCQ) in the “Study of Anti- Malarials in Incomplete Lupus Erythematosus” or SMILE trial. The primary objective is to determine whether HCQ treatment can prevent acquisition of additional clinical and immunologic features that define SLE. The major secondary objectives are to determine whether HCQ treatment: (1) lessens lupus disease activity as measured by standard scoring indices; (2) improves patient reported outcomes (3) prevents accumulation of immunologic abnormalities including autoantibodies and cytokines and (4) has an acceptable toxicity profile. The specific aims of this proposal are: 1. To carry out a double-blind, placebo-controlled, multicenter, randomized trial of HCQ vs. placebo in patients with ILE. The study tests the hypothesis that early use of HCQ can modify disease features so that accumulation of abnormalities leading to a classification of SLE can be significantly slowed. 2. To determine effects of HCQ on disease activity and patient-reported outcomes in patients with ILE. 3. To characterize the immunologic profile of HCQ in ILE-treated patients. Autoantibodies, cytokines and chemokines will be measured on multiplex arrays for developing insights into underlying mechanisms. 4. To quantitatively assess the incidence of ophthalmologic toxicity in HCQ-treated ILE patients. All enrolled patients will have standardized ophthalmologic examinations before and after study treatment. Recommendations for use and monitoring in this patient population will be developed. The SMILE trial will determine whether or not HCQ should be given to ILE patients, will provide insights into the appropriate target population, and will propose candidate biomarkers to guide treatment decisions. While not part of the Precision Medicine Initiative®, SMILE is consistent with its goals. It will be the first step towards testing the feasibility of disease prevention studies in SLE and will accumulate biological samples in a repository that will be available to the lupus research community for further in-depth mechanistic studies.