Identification of Biological Predictive Factors of Clinical Response to Ustekinumab in Patients With Anti-Tumor Necrosis Factor (TNF) Antagonists Refractory Crohn's Disease: Interest of Dosage of C Reactive Protein (CRP), Calprotectin, Ustekinumab Through Levels and Antibodies
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 8.
研究概览
简要总结
Ustekinumab is a fully human Immune Globulin Gk (IgGk) monoclonal antibody against the common p40 subunit of interleukin-12 and interleukin-23, which are implicated in the pathogenesis of inflammatory bowel disease. Its efficiency to induce and maintain clinical response in patients with anti TNF resistant Crohn's disease has been proved in several clinical trials, and the profile of safety of this treatment was good, but the investigators have few data about biological characteristics of patients treated by Ustekinumab, particularly about ustekinumab through levels and rate of patients developing anti ustekinumab antibodies during the induction and maintenance stages, and no predictive factors of clinical response have been identified yet.
The aim of this study will be to assess the evolution of biological markers of inflammation and ustekinumab trough levels and antibodies, in responders and non responders patients treated by ustekinumab, in order to identify predictive factors of clinical response.
The investigators will perform a prospective observational study, including the patients followed in the University hospital center of Lyon and treated by ustekinumab for a moderate to severe Crohn's disease (with a HBI score≥4 ). All the patients included will have been previously treated by at least one anti TNF and/or Vedolizumab, with specified criteria for a primary non response, a secondary loss of response or unacceptable side effects.
Then, clinical and biological data will be collected for each patient at the inclusion, and then at weeks 4, 8, 16, 24: HBI score, sides effects, extra intestinal manifestations, steroids withdraw, CRP, calprotectin, ustekinumab trough levels and ustekinumab antibodies.
The investigators will compare responding and non responding patients at week 16 (end of the induction period) according to these data.
The hypothesis the investigators state is that an early and significant decrease of the inflammation markers in blood and stools associated with a high ustekinumab through level in blood is associated with a clinical response at week 16 in the patients treated by ustekinumab
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 18 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years old
- •Man or non pregnant woman
- •Diagnostic attested of Crohn's disease
- •Active Crohn's disease, with HBI score ≥ 4
- •Previous treatment by at least one anti TNF and / or vedolizumab,, with primary non response, secondary loss of response or unacceptable side effects
- •Formal indication of treatment by ustekinumab
- •Patient informed and not opposed to his participation at the study
排除标准
- •Pregnancy
- •Evolutive cancer
- •Evolutive and uncontrolled infection
- •Psychiatric pathology that could interfere with the follow-up
- •Refusal of the patient
结局指标
主要结局
Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 8.
时间窗: Week 8
Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample
次要结局
- Dosage in blood at week 16(Week 16)
- Dosage of calprotectin in stools at week 8(Week 8)
- Dosage of calprotectin in stools at week 16(Week 16)
- Clinical evaluation at week 24(Week 24)
- Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 4.(Week 4)
- Dosage in blood at week 4(Week 4)
- Physical evaluation at week 16(Week 16)
- Physical evaluation at week 4(Week 4)
- Clinical evaluation at week 8(Week 8)
- Dosage of calprotectin in stools at week 4(Week 4)
- Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 16.(Week 16)
- Measurement of serum ustekinumab trough concentrations (expressed in microg/mL) at week 24.(Week 24)
- Dosage in blood at week 8(Week 8)
- Dosage in blood at week 24(Week 24)
- Physical evaluation at week 24(Week 24)
- Clinical evaluation at week 16(Week 16)
- Dosage of calprotectin in stools at week 24(Week 24)
- Physical evaluation at week 8(Week 8)
- Clinical evaluation at week 4(Week 4)