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

不完全性红斑狼疮 (SMILE) 抗疟药研究

• 批准号: 10348096
• 负责人: DAVID R KARP
• 金额: $ 93.48万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10348096
• 关键词: Adverse effects; Antimalarials; Antinuclear Antibodies; Autoantibodies; Autoimmune Diseases; Biological; Biological Markers; Blood; Chronic Disease; Classification; Clinical; Clinical Trials; Communities; Data; Development; Diagnosis; Disease; Double-Blind Method; Early Diagnosis; Early identification; Early treatment; Enrollment; Exhibits; Genes; Goals; Hydroxychloroquine; Immunologic Markers; Immunologics; Incidence; Individual; Intervention; Laboratories; Longevity; Lupus; Lupus Erythematosus; Measures; Modification; Monitor; Morbidity - disease rate; Observational Study; Onset of illness; Ophthalmology; Organ; Patient Outcomes Assessments; Patients; Persons; Pharmaceutical Preparations; Placebo Control; Placebos; Population; Population Intervention; Populations at Risk; Precision Medicine Initiative; Prevention strategy; Randomized; Recommendation; Research; Research Personnel; Risk; Safety; Sampling; Signs and Symptoms; Standardization; Suggestion; Symptoms; Systemic Lupus Erythematosus; Target Populations; Testing; Therapeutic; Therapeutic Intervention; Time; Toxic effect; Treatment-related toxicity; Woman; candidate marker; chemokine; clinical practice; cytokine; design; disorder prevention; evidence base; feasibility testing; high risk; improved; improved outcome; indexing; insight; mortality; patient population; prevent; randomized trial; repository; response biomarker; standard measure

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.

项目总结/摘要 系统性红斑狼疮（SLE）可导致主要器官损伤，并缩短相对年轻人的寿命。 人士早期诊断和治疗对改善SLE患者的预后至关重要。然而，在这方面， 早期治疗干预的循证方法和这些方法的适当目标人群 没有干预措施。我们建议抗核抗体阳性的人 （ANA）和谁也表现出一些其他功能，用于分类系统性红斑狼疮，是在高风险的 发展成这种疾病的全身形式。这些人，谁拥有显着水平的抗核抗体 从狼疮分类标准中增加1或2项，被认为是不完全狼疮 红斑或ILE。我们建议在“抗-羟氯喹（HCQ）的研究”中用HCQ治疗ILE患者。 不完全红斑狼疮中的疟疾”或SMILE试验。主要目的是确定是否 HCQ治疗可以防止获得额外的临床和免疫学特征，定义系统性红斑狼疮。 主要的次要目的是确定HCQ治疗是否：（1）减少狼疮疾病活动， 通过标准评分指数测量;（2）改善患者报告的结局（3）防止 包括自身抗体和细胞因子在内的免疫学异常和（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与安慰剂的双盲、安慰剂对照、多中心、随机试验 关于ILE该研究验证了早期使用HCQ可以改变疾病特征的假设， 可显著减缓导致SLE分类的异常的累积。 2.确定HCQ对ILE患者疾病活动和患者报告结局的影响。 3.描述接受过肠梗阻治疗的患者中HCQ的免疫学特征。自身抗体、细胞因子和 将在多重阵列上测量趋化因子，以深入了解潜在的机制。 4.定量评估HCQ治疗的ILE患者的眼科毒性发生率。所有入组 患者将在研究治疗前后进行标准化眼科检查。 将制定在该患者人群中使用和监测的建议。 SMILE试验将确定是否应给予ILE患者HCQ，将提供以下见解 适当的目标人群，并将提出候选生物标志物，以指导治疗决策。而 SMILE不属于精准医学计划®，但与其目标一致。这将是迈向 测试SLE疾病预防研究的可行性，并将积累生物样本， 储存库，将提供给狼疮研究界进一步深入的机制研究。