Identification of Predictive Biomarkers for Response to Biologic Therapies and Tofacitinib in Inflammatory Bowel Disease by Proteomic and Mass Cytometry Approaches
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 180
- 试验地点
- 21
- 主要终点
- Identify predictive tissue and blood biomarkers for response to biologic therapies and tofacitinib in Crohn´s disease and ulcerative colitis
研究概览
简要总结
Prospective, multicentre trial which the biologic treatment will be initiated by clinical indication. The treatment selection anti-TNFα (infliximab, adalimumab or golimumab), vedolizumab, ustekinumab and tofacitinib will be made at the discretion of the clinician. There will be no random assignment of treatment. The drugs will be used in the approved indications and conditions of use.
详细描述
Background
IBD, including CD and UC, is a chronic disorder of unknown etiology that involves a pathological response of the immune system, resulting in chronic inflammation of the gastrointestinal tract. IBD generally affects young patients, being a highly disabling disease. Unfortunately IBD has no current treatment, so the therapeutic goal is to keep the inflammatory process under control in order to prevent the onset of symptoms and the development of further complications.
The complexity and costs associated with the treatment of IBD make it a very relevant disease. Specifically in the USA, where it is one of the five diseases with the greatest social burden, with an annual cost of 1,700 million dollars for health services. In Europe, the annual costs (direct and indirect) associated with IBD exceed 25,000 million euros. Together, this highlights the strategic importance of IBD for society, including both patients and the health system.
IBD prevalence is high, affecting more than 1.6 million inhabitants in the US and more than 2.2 million in Europe. On the other hand, its incidence varies widely depending on the different countries. Nevertheless, in a generalized manner, it is increasing rapidly, probably due to the "westernization" of lifestyles. Indeed, a large multicenter study leaded by the host institution suggests that the current incidence is greater than previously described.
In addition, the cost associated with IBD diagnosis and treatment is increasing over time, either because of the costs associated with the treatment itself or due to the greater complexity of the diagnostic tests and tools to which these patients are subjected.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •Over 18 years.
- •Diagnosis of IBD according to the criteria of the European Crohns and Colitis Organization (ECCO).
- •Have indication of treatment with a biologic drug or tofacitinib.
- •Be the first received drug with a given mechanism of action (anti-TNFα, anti-α4β7, anti-p40 or Janus kinase (JAK) inhibitor).
- •Have endoscopic activity of IBD within 1 month of starting the biologic treatment (see definitions section: SES-CD ≥ 3 in CD and endoscopic sub-index of May ≥ 2 in UC).
- •In the case of CD, receive the biologic treatment by luminal activity (not perianal).
排除标准
- •Under 18 years old.
- •Having an immune-mediated disease other than IBD at the baseline visit.
- •Having a neoplasm or an active infection at the time of the baseline visit.
- •Pregnancy or lactation.
- •Alcohol or drug abuse.
- •Abdominal surgery in the last 6 months.
- •Colectomy in patients with UC.
- •Active infection with hepatitis B, C or HIV virus.
- •Indication of biologic treatment for a cause other than IBD.
- •Indication of biologic treatment to prevent postoperative recurrence in CD.
- •Have previously received a drug with the same mechanism of action of the drug indicated by your doctor (anti-TNFα, anti-α4β7, anti-p40 or JAK inhibitor).
- •Refusal to give consent for participation in the study.
- •Group 2: patients without IBD
- •Inclusion Criteria:
- •Patients not diagnosed with IBD, or other inflammatory, allergic, malignant or autoimmune diseases, where a ileocolonoscopy is performed due to the normal clinical practice.
- •Exclusion Criteria:
- •Under 18 years old.
- •Advanced chronic disease or any other pathology that prevents the follow-up of the protocol of this study.
- •Pregnancy or lactation.
- •Active infection with hepatitis B, C or HIV virus.
- •Alcohol or drug abuse.
- •Finding of macroscopic alterations during the ileocolonoscopy, or finding of relevant inflammatory alterations in the biopsies obtained during the ileocolonoscopy.
- •Refusal to give consent for participation in the study.
研究组 & 干预措施
Patients with treatment
Infliximab (Infusion 5mg/kg milligram(s)/Kilogram-Intravenous use) per clinical practice, or adalimumab (Subcutaneus 40 mg milligram(s)) per clinical practice, or golimumab (subcutaneus 50 mg milligram(s)) per clinical practice, or vedolizumab (infusion 300 mg milligram(s)) per clinical practice or ustekinumab (subcutaneous 90 mg milligram(s)) per clinical practice or tofacitinib (oral 5mg bid oral) per clinical practice
干预措施: Infliximab or adalimumab or golimumab or vedolizumab or ustekinumab or tofacitinib (Biological)
结局指标
主要结局
Identify predictive tissue and blood biomarkers for response to biologic therapies and tofacitinib in Crohn´s disease and ulcerative colitis
时间窗: 14 weeks
will be calculated for each of the selected biomarkers: sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio
次要结局
- Identify non-invasive blood biomarkers of endoscopical inflammation(14 weeks)
- Generate a collection of biological simple (Blood sample, urine sample, stool sample, biopsy simple)(14 weeks)
- Evaluate the effect of the treatment on the immune subsets and study the signaling pathways specifically modulated(14 weeks)