Influence of HLA-DQA1*05 Genotype in Adults With Inflammatory Bowel Disease and Anti-TNF Treatment With Proactive Therapeutic Drug Monitoring. A Prospective Multicenter Study.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 280
- 试验地点
- 1
- 主要终点
- Corticosteroid-free clinical remission and treatment maintenance at week 54
研究概览
简要总结
HLA-DQA1*05 variant carriers are at risk of developing antibodies against infliximab and adalimumab with reduced TNF antagonist persistence.
The impact of proactive therapeutic drug monitoring (PTDM) on this association has been barely assessed.
Therefor, we propose a cohort study including adult patients with Crohn's disease and ulcerative colitis treated with TNF antagonists under proactive therapeutic drug monitoring.
Our hypothesis is that, proactive therapeutic drug monitoring could be an alternative to combination treatment with immunomodulators to increase TNF-antagonists' persistence in HLA-DQA1*05 carriers.
详细描述
Population study: patients with inflammatory bowel disease and initiation of anti-TNF therapy
Inclusion and exclusion criteria
The inclusion criteria are:
- Patient diagnosed with inflammatory bowel disease based on clinical, endoscopic, and pathological criteria according to ECCO criteria.
- Initiation of anti-TNf, including infliximab and adalimumab.
- Subjects naïve to biological treatment
- Age >18 years.
The exclusion criteria are:
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
- •Diagnosis of inflammatory bowel disease according to ECCO criteria.
- •Older than 18 years
- •Subjects naïve to biological treatment
- •Anti-TNF treatment initiation (infliximab or adalimumab) due to intestinal activity and/or perianal disease.
- •Avaibility to evaluate HLA DQA1*05 status
- •Proactive therapeutic drug monitoring of anti-TNF levels
排除标准
- •Initiation of anti-TNF treatment as prevention of post-surgical recurrence in Crohn's disease during the first 12 months after surgery or, afterwards, if endoscopic recurrence with a Rutgeerts 0-
- •Initiation of anti-TNF treatment under combo treatment with immunomodulator. Prior initiation of immunomodulator or prior use and suspension would not be a contraindication.
- •Initiation of anti-TNF treatment due to extraintestinal activity.
- •Initiation of anti-TNF treatment by a non-gastroenterologist specialist.
- •Initiation of anti-TNF treatment during pregnancy.
研究组 & 干预措施
HLA-DQA1*05 variant carriers
干预措施: Tumor necrosis factor (TNF)-alpha inhibitors (Drug)
HLA-DQA1*05 non-carriers
干预措施: Tumor necrosis factor (TNF)-alpha inhibitors (Drug)
结局指标
主要结局
Corticosteroid-free clinical remission and treatment maintenance at week 54
时间窗: Week 54
Corticosteroid-free clinical remission was defined as Harvey Bradshaw score \<5 for Crohn's disease or partial Mayo score ≤2 for ulcerative colitis with no item exceeding one point, without corticosteroid
次要结局
- Proportions of primary failure between both groups(week 12)
- To compare drug levels at week 6 (infliximab) and week 4 (adalimumab) in subjects with a standard induction(week 4 or 6)
- Proportion of subjects with anti-drug antibodies at the end of induction and week 54.(week 54)
- Corticosteroid-free clinical response and remission at week 12.(week 12)
- Proportions of patients with clinical-biochemical remission at week 54.(week 54)
- Proportions of endoscopic remission at week 54 between both groups.(week 54)
- Proportions of patients with ultrasound remission at week 12 and 24(week 12 and 24)
研究者
Esteban Fuentes-Valenzuela
MD
Hospital del Río Hortega