Scrutinizing the Heterogeneity of Systemic Lupus Erythematosus: Defining Phenotypes
试验速览
- 阶段
- 不适用
- 入组人数
- 950
- 试验地点
- 1
- 主要终点
- Disease Course Patterns
研究概览
简要总结
SLE disease course is characterized by unpredictable relapses and remissions in the majority of patients. However, in a small proportion (approximately 5%), SLE presents with a monophasic pattern, meaning that these patients have active disease before and immediately after diagnosis and after some time they achieve prolonged remission (for 12 years on average). Interestingly, about half of these patients do so and require no medications. On the other end of the clinical spectrum, approximately 50% of the patients demonstrate persistent disease activity and usually have the highest risk for developing co-morbidities and irreversible damage. A major goal of clinical research in SLE is to improve disease management based on disease course. By better characterizing SLE disease course we hope to better identify patients early in the disease course for targeted therapies to prevent and or reduce future SLE complications.
The overall objective of our project is to define distinct phenotypes of SLE based on disease course, clinical features, pathogenic mechanisms, genetic factors and relevant biomarkers.
详细描述
Specific aims of this study are:
- To test the clinical impression of the disease courses by modeling the course of the disease in each of three sub-populations of patients where it is anticipated that one sub-population will experience relapsing and remitting disease activity, one will experience persistently active disease and another will exhibit a monophasic pattern.
- To develop predictive models for group membership to enhance the accuracy of prognosis.
- To test these models in the inception cohort of SLE patients within the Toronto Lupus Cohort.
Study Design: Retrospective longitudinal observational cohort
Patients will be categorised into three disease courses:
I. Relapsing-remitting II. Persistently active III. Monophasic Relapsing/remitting is defined as periods of disease activity SLEDAI-2K of 4 or more, (but if only 4 cannot be from serology alone) less than 50% of the time alternating with periods of inactivity (SLEDAI-2K <4) over the course of follow-up.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients enrolled in the study for aims 1 and 2 must meet the following inclusion criteria:
- •≥4 American College of Rheumatology (ACR) criteria or 3 ACR criteria plus a typical histological lesion of SLE on renal or skin biopsy.
- •Patients must have a minimum of 2 assessment visits.
- •Patients enrolled in the study for aim 3 must meet the following criteria:
- •Must be inception patients seen within one year of diagnosis of SLE
- •≥4 American College of Rheumatology (ACR) criteria or 3 ACR criteria plus a typical histological lesion of SLE on renal or skin biopsy.
- •Patients must have a minimum of 6 assessment visits to ensure categorization into one of the disease courses derived in aims 1 and 2
排除标准
- •Patients who have not had 2 assessment visits for aims 1 and 2
- •Patients who have not had 6 assessments for aim 3.
结局指标
主要结局
Disease Course Patterns
时间窗: 6 months
All 49,000 visits within the Toronto Lupus Cohort will be probed for patterns of disease activity using SLEDAI-2K measurements on each assessment. A finite mixture model will be fitted to the data to accommodate for three sub-populations of patients. Disease course for each sub-populations will be defined in terms of multistate model where the states reflected meaningfully different degrees of disease activity as measured by the SLEDAI-2K scores.
次要结局
未报告次要终点
研究者
Murray B Urowitz, MD FRCP(C)
Priniple Investigator
University Health Network, Toronto