Investigation of Immunological and Pharmacological Factors for Response to Adalimumab in Rheumatoid Arthritis, With Analysis of CD4 + Follicular Helper T Subpopulations
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 59
- 试验地点
- 2
- 主要终点
- Patient responding or not responding to treatment with Adalimumab at 6 months defined by a value of Disease Activity Score 28 (DAS 28) ≤ 3.2.
研究概览
简要总结
Interventional study with minimal risks and constraints, prospective, mono-centric.
详细描述
Rheumatoid arthritis (RA) is a chronic inflammatory disease with synovial tropism, characterized by joint pain and swelling, secondary to inflammation of the synovial membrane and which can lead to joint destruction, with the risk of a major functional disability. Biological treatments have revolutionized its management over the past 15 years. However, they are not effective in all patients, they are expensive, and are not without side effects sometimes severe.
Currently, there is no predictive factor for response to biotherapy beyond the severity criteria of rheumatoid arthritis (presence of erosions, presence of anti-Citrullinated Protein Antibody (ACPA), importance of biological and clinical inflammation ).
The role of T lymphocytes and B lymphocytes has been widely studied in rheumatoid arthritis. The activity of rheumatoid arthritis is associated with a Th1 and Th17 type CD4 + T polarization, with pro-inflammatory cytokine production and decreased Treg activity.
In recent years, a population of CD4 + T lymphocytes, Tfh (T follicular helper cells) has been demonstrated and seems likely to play an important role in the pathogenesis of rheumatoid arthritis. Physiologically these cells were initially described in the secondary lymphoid organs where they are essential for the survival and differentiation of B lymphocytes into antibody-secreting cells. More recently, they have been described in the blood (c Tfh for circulating T follicular helper cells) and appear to be a reflection of Tfh activity in tissues.
Several studies have focused on c Tfh in rheumatoid arthritis. A significantly higher level of c Tfh was observed in rheumatoid arthritis than in healthy controls. A significant positive correlation was also observed between the level of c Tfh and the titre of ACPA and between the rate of c Tfh and the activity of the rheumatoid arthritis, measured by the Disease Activity Score (DAS). However, each research group characterized the c Tfh t with different markers, which limits the comparison of the different results obtained.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Rheumatoid arthritis diagnosed according to EULAR 2010 criteria (European League Against Rheumatism);
- •Active rheumatoid arthritis, defined by DAS 28> 3.2;
- •Corticotherapy systemic ≤ 15mg /day, stable for ≥ 15 days;
- •Refractory or intolerant rheumatoid arthritis with at least one chemical background treatment;
- •Previous biological treatment stopped for ≥ 3 months for monoclonal antibodies (except Rituximab) and 15 days for Etanercept;
- •Patients who have given written informed consent.
- •For healthy volunteers: subjects aged 18 coming to the French blood establishment of Rennes for a donation of blood
排除标准
- •Patient minor;
- •Presence of a contraindication to biological treatment;
- •Previous treatment with Rituximab;
- •Vaccination or surgery in the month preceding the study or planned within 3 months of inclusion;
- •Patient not affiliated to social security;
- •Major persons subject to legal protection (safeguard of justice, curatorship, guardianship), persons deprived of their liberty.
- •For healthy volunteers: Minor subject ; Subject not affiliated with social security ; Major persons subject to legal protection (legal safeguards, guardianship, tutorship), persons deprived of their liberty
结局指标
主要结局
Patient responding or not responding to treatment with Adalimumab at 6 months defined by a value of Disease Activity Score 28 (DAS 28) ≤ 3.2.
时间窗: 6 months
Disease Activity Score 28 (DAS 28) calculated in every patients after clinical examination.
次要结局
- Patient responding or not responding to treatment with Adalimumab at 6 months and 1 year defined by the HAQ scores(6 and 12 months)
- Second derivative spectrometric profiles(Baseline and 3 monts)
- Patient responding or not responding to treatment with Adalimumab at 6 months and 1 year defined by the CDAI scores(6 and 12 months)
- Patient responding or not responding to treatment with Adalimumab at 1 year defined by a value of Disease Activity Score 28 (DAS 28) ≤ 3.2.(12 months)
- Patient responding or not responding to treatment with Adalimumab at 6 months and 1 year defined by the SDAI scores(6 and 12 months)
- Residual plasmatic Adalimumab concentration(3, 6 and 12 months)
- Count of Anti-Adalimumab antibody(3, 6 and 12 months)