Scrutinizing the Heterogeneity of SLE: Defining Phenotypes
Scrutinizing the Heterogeneity of Systemic Lupus Erythematosus: Defining Phenotypes
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.
調査の概要
状態
条件
詳細な説明
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.
Persistently active disease is defined as SLEDAI-2K of 4 or more, (but if only 4 cannot be from serology alone), in greater than 80% of the visits, or no 2 consecutive visits with SLEDAI-2K < 4.
Monophasic course is defined as disease activity SLEDAI-2K of 4 or more, (but if only 4 cannot be from serology alone) for an initial period of less than 3 years followed by resolution and inactive disease (SLEDAI-2K of 0 excluding serology) for at least 5 years.
Clinical and laboratory characteristics, therapies and outcomes for each subgroup will be described. Identification of all clinical and laboratory features of lupus contained in the CRF will be compared for each group, as well as the medications prescribed.
研究の種類
入学 (予想される)
連絡先と場所
研究場所
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Ontario
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Toronto、Ontario、カナダ、M5T2S8
- University Health Network
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参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
Patients with SLE have been followed prospectively at the University of Toronto Lupus Clinic since 1970. All patients ≥4 or more of the 1997 ACR criteria for SLE, or have 3 criteria and a typical lesion of SLE on renal or skin biopsy. Patients are evaluated at 2-6 month intervals according to a standard protocol which includes a detailed clinical history, physical examination, and laboratory evaluation . It includes all information necessary to calculate disease activity and damage indices, as well as comorbidities. Disease activity is assessed by the SLE Disease Activity Index 2000 (SLEDAI-2K) , and accumulated damage by the SLICC/ACR damage index (SDI) .
To date there are 1767 patients with 2 or more visits registered in the Lupus Clinic Database, with 43079 assessments recorded. Their characteristics are shown in Table 1.
説明
Inclusion Criteria:
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
Exclusion Criteria:
- Patients who have not had 2 assessment visits for aims 1 and 2
- Patients who have not had 6 assessments for aim 3.
研究計画
研究はどのように設計されていますか？
デザインの詳細
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Disease Course Patterns
時間枠：6 months
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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.
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6 months
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協力者と研究者
協力者
捜査官
- 主任研究者：Murray Urowitz、University Health Network and University of Toronto
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
全身性エリテマトーデスの臨床試験
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Beijing Immunochina Medical Science & Technology...まだ募集していません体系的なループスerythematosusを治療するのは困難です