Prospective Observational Study Evaluating the Safety and Efficacy of Immunomodulatory Therapies in Refractory Inflammatory and Autoimmune Diseases
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 80
- 试验地点
- 17
- 主要终点
- proportion of complete remission from the disease at week 24
研究概览
简要总结
Inflammatory and/or autoimmune diseases represent a very broad group of diseases with highly variable clinical features, including - but not limited to - systemic connectivites and vasculitides. As these diseases are rare and heterogeneous, it is difficult to conduct randomized clinical trials in this setting. Refractory cases are therefore treated with drugs that are already available on the market for other indications in more frequent and clinically homogeneous diseases, such as inflammatory rheumatism and haematological malignancies.
Prescribing treatments from other specialties (e.g. rheumatology and oncohaematology) is a reality in the clinical practice of internists and immunologists, often representing an excellent solution for difficult-to-treat inflammatory and/or autoimmune diseases. As these molecules are prescribed without the availability of standardized data, it is essential to collect them prospectively to better characterize the efficacy and tolerability of these new therapeutic options in severe inflammatory and/or autoimmune diseases.
详细描述
Inflammatory and/or autoimmune diseases represent a very broad group of diseases with highly variable clinical features, including - but not limited to - systemic connectivites and vasculitis. Individually, they are very rare diseases, generally estimated in terms of the number of cases per 100,000 or 1,000,000 inhabitants. However, if we consider all immune-mediated inflammatory diseases, it is estimated that they affect 4.5% of the world's population .
Despite their extreme heterogeneity in terms of clinical presentation, these diseases share several key pathogenic mechanisms. For example, over the past two decades, adaptive immunity has been successfully targeted with several monoclonal antibodies directed against B lymphocytes (e.g. rituximab, an anti-CD20) and co-stimulation between B and T lymphocytes (e.g. abatacept, a CTLA-4 agonist). Targeting cytokines common to several of these diseases has also proved effective in their management, in particular anti-TNF alpha and anti-IL-6, produced by cells of the innate and adaptive immune systems.
Although these molecules have ushered in a new era in the management of inflammatory and/or autoimmune diseases, not all patients are yet fully controlled, representing a major challenge in clinical practice.
Refractory cases are then treated with drugs that are already available on the market for other indications in more frequent and clinically homogeneous diseases, such as inflammatory rheumatism and haematological malignancies.
Certain therapeutic targets stand out. The first is the cytokine IL-17, which plays a crucial role in the polarization of T helper 17 (Th17) lymphocytes and orchestrates the adaptive response detectable in the blood and target tissues of various inflammatory and/or autoimmune diseases.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients over 18 years
- •Enrolled in the French national social security system
- •Diagnosis of an inflammatory/autoimmune disease meeting internationally accepted classification criteria;
- •Clinical activity of their disease with biological and/or radiological signs, refractory to conventional therapeutic lines, requiring a new treatment as an addition or replacement according to clinical judgment.
- •No formal contraindication to the new therapeutic class.
排除标准
- •Pregnancy or breast-feeding (for women of childbearing potential, a negative serum pregnancy test will be required);
- •History of severe immunosuppression, HIV or HBsAg positive.
- •Positive QuantiFERON test result (QFT-TBGIn-Tube) for active tuberculosis (latent tuberculosis under treatment may be included).
- •Have received live vaccines in the 3 months preceding the start of treatment.
- •History of malignant tumor within the last 5 years.
- •Severe renal insufficiency (creatinine clearance <30mL/min/1.73m²)
- •Liver dysfunction defined by aspartate transaminase (AST) or alanine transaminase (ALT) levels ≥ 5 times the upper limit of normal.
- •Blood count abnormality:
- •Platelets < 50 x 103/mm3
- •Neutropenia < 1000/mm3
- •Hemoglobin < 8 g/dL
结局指标
主要结局
proportion of complete remission from the disease at week 24
时间窗: week 24
The primary outcome will be the proportion of complete remission from the disease at week 24 : 1. absence of all clinical signs and symptoms ; 2. normalization of fibrinogen and CRP values; 3. absence of radiological signs of active disease (stable or improved imaging).
次要结局
- Evaluate the proportion of patients in clinical, biological or radiological remission(week 12 and week 48)
- Cumulative incidence of relapse (i.e., recurrence of clinical symptoms associated with biological and/or radiological inflammatory activity following complete remission)(weeks 12, 24, 36 and 52)
- Cumulative incidence of remission according to primary endpoint definitions(weeks 12, 36 and 52)
- Evaluate changes in median disease-specific activity scores(weeks 12, 24, 36 and 52)
- Cumulative prednisone dose(weeks 12, 24, 36 and 52)
- Cumulative incidence of serious adverse events (i.e., those requiring hospitalization or death) at weeks 12, 24, 36 and 52(weeks 12, 24, 36 and 52)
- Evolution of circulating immune cell populations & cytokines under treatment(Weeks 0, 1, 2, 4, 12, 24, and 52)