Addition of Azathioprine to the Switch of Anti-TNF Drug in IBD Patients in Clinical Relapse With Undectectable Anti-TNF Trough Levels and Anti-drug Antibodies : a Prospective Randomized Trial
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- clinical failure
研究概览
简要总结
Loss of response under anti-TNF is frequent. 20% of patients with clinical relapse present an immune mediated pharmacokinetic failure. In the last AGA recommendations, switch to another anti-TNF drug is suggested with no indication of immunosuppressive agent. In a recent study, 70% of patients with an immunogenic failure to a first anti-TNF agent developed a new immunogenic failure to the second anti-TNF drug using alone.
详细描述
The aim of the study in these patients with an immune mediated pharmacokinetic failure was to compare two strategies:
Switch to a second anti-TNF alone or switch to a second anti-TNF with addition of azathioprine
Comparing rates of clinical failure, rates of immunogenic failure and finally adverse events during a follow-up of 24 months
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
open label study
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
- •IBD Patients in clinical failure under anti-TNF (Infliximab (IFX) or Adalimumab (ADA) in monotherapy at the optimal dose) ADA: 40mg/7 days, IFX: 10mg/kg/8 weeks Active disease CD: HBI > 5 with Calprotectin > 250 µg/g stool UC: Total Mayo Score > 4 with an endoscopic subscore > 1 Anti-TNF monotherapy for at least 4 months and optimization for at least two months
- •Patients with an immune mediated PK failure Undetectable rates of anti-TNF and high Ab against anti-TNFs > 20ng/mL for ATI and AAA (Elisa Theradiag) on two consecutive samples
- •Patients who have agreed to and signed the consent form
排除标准
- •Unclassified colitis
- •Pregnant woman
- •Crohn's disease CD with a exclusive anoperineal phenotype
- •Contraindication or intolerance to azathioprine
- •Primary non-responder patients To the first anti-TNF or After the switch to a - second anti-TNF
研究组 & 干预措施
switch to anti-TNF alone
Switch to the second anti-TNF drug alone (infliximab or adalimumab)
Loss of response under Infliximab: 10 mg/kg IV every 8 weeks Randomization to: Adalimumab: induction 160/80 mg SC and Maintenance 40 mg EOW SC OR Loss of response under Adalimumab: 40mg EW SC Randomization to: Infliximab: 5mg/kg IV at W0, W2, W6 and every 8 weeks.
干预措施: Switch to a second anti-TNF drug alone (Drug)
switch to anti-TNF with addition of azathioprine
Switch to anti-TNF (infliximab or adalimumab) with addition of azathioprine
Loss of response under Infliximab: 10 mg/kg IV every 8 weeks Randomization to: Adalimumab: induction 160/80 mg SC and Maintenance 40 mg EOW SC with azathioprine 2.5 mg/kg/day OR
Loss of response under Adalimumab: 40mg EW SC Randomization to:
Infliximab: 5mg/kg IV at W0, W2, W6 and every 8 weeks with azathioprine 2.5 mg/kg/day.
干预措施: addition of azathioprine (Drug)
结局指标
主要结局
clinical failure
时间窗: 24 months
clinical relapse or serious adverse event requiring stopping treatment during follow up
次要结局
未报告次要终点
研究者
Philippe VEDRINES
head of gastroenterology unit and principal investigator
Védrines, Philippe, M.D.