Olsen Nancy J, James Judith A, Arriens Cristina, Ishimori Mariko L, Wallace Daniel J, Kamen Diane L, Chong Benjamin F, Liao Duanping, Chinchilli Vernon M, Karp David R
Division of Rheumatology, Department of Medicine, Penn State MS Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA.
Oklahoma Medical Research Foundation, 825 N.E. 13th Street, Oklahoma City, OK, 73104, USA.
Trials. 2018 Dec 20;19(1):694. doi: 10.1186/s13063-018-3076-7.
Onset of systemic lupus erythematosus (SLE) is preceded by a preclinical phase characterized by expression of autoantibodies and nonspecific clinical symptoms. Hydroxychloroquine is a treatment for lupus that is widely used based on longstanding experience and a very good safety profile. Existing data suggest that treatment with hydroxychloroquine may postpone the onset of disease. However, prospective studies that prove and quantify the efficacy of hydroxychloroquine in the preclinical phase of lupus have not been done. This study will test the hypothesis that early hydroxychloroquine use can prevent accumulation of clinical abnormalities and modify immune responses that define SLE.
A randomized, double-blind, placebo-controlled trial of hydroxychloroquine vs placebo will be conducted. Participants will have incomplete lupus erythematosus as defined by the presence of antinuclear antibody (ANA) positivity at a titer of 1:80 or greater, as well as one or two additional criteria from the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria. The age range will be 15-45 years and the treatment phase will be 96 weeks. The primary endpoint will be the increase in the number of features of SLE defined by the 2012 SLICC classification schema. Secondary outcomes will include the proportion of participants who transition to a classification of SLE as defined by SLICC criteria.
A major challenge for improving therapies in patients with SLE is early detection of disease. The ANA test that is widely used to screen for SLE has low specificity and interpretation of its significance is challenging. The Study of Anti-Malarials in Incomplete Lupus Erythematosus (SMILE) trial will provide insights into the appropriate target population for intervention, and will assess whether hydroxychloroquine can slow progression as measured by the accumulation of criteria. Ophthalmologic safety in this population will be assessed. The study will investigate candidate biomarkers that will guide treatment decisions and will accumulate a specimen biobank that will be available to the lupus research community for further in-depth mechanistic studies. This trial is a first step toward testing the feasibility of disease prevention strategies in SLE.
ClinicalTrials.gov, NCT 03030118 . Registered on 24 January 2017.
系统性红斑狼疮（SLE）发病前存在一个临床前期阶段，其特征为自身抗体表达和非特异性临床症状。羟氯喹是一种用于治疗狼疮的药物，基于长期经验和良好的安全性被广泛使用。现有数据表明，使用羟氯喹治疗可能会推迟疾病的发作。然而，尚未有前瞻性研究证实并量化羟氯喹在狼疮临床前期阶段的疗效。本研究将检验早期使用羟氯喹可预防临床异常累积并改变定义SLE的免疫反应这一假设。
将进行一项羟氯喹与安慰剂对比的随机、双盲、安慰剂对照试验。参与者将患有不完全性红斑狼疮，定义为抗核抗体（ANA）滴度为1:80或更高且呈阳性，以及符合2012年系统性红斑狼疮国际协作临床中心（SLICC）分类标准中的一至两条额外标准。年龄范围为15至45岁，治疗阶段为96周。主要终点将是2012年SLICC分类方案定义的SLE特征数量的增加。次要结局将包括根据SLICC标准转变为SLE分类的参与者比例。
改善SLE患者治疗方法的一个主要挑战是疾病的早期检测。广泛用于筛查SLE的ANA检测特异性较低，对其意义的解读具有挑战性。不完全性红斑狼疮抗疟药研究（SMILE）试验将为合适的干预目标人群提供见解，并将评估羟氯喹是否能减缓疾病进展（以标准累积衡量）。将评估该人群的眼科安全性。该研究将调查可指导治疗决策的候选生物标志物，并将积累一个样本生物库，供狼疮研究界用于进一步深入的机制研究。该试验是测试SLE疾病预防策略可行性的第一步。
ClinicalTrials.gov，NCT 03030118。于2017年1月24日注册。
