De-escalation of Anti-TNF Therapy in Adolescents and Young Adults With IBD With Tight Faecal Calprotectin and Trough Level Monitoring
试验速览
- 阶段
- 4 期
- 状态
- Enrolling By Invitation
- 入组人数
- 148
- 试验地点
- 7
- 主要终点
- cumulative incidence of out-of-range fecal calprotectin results at 48 weeks follow-up
研究概览
简要总结
BACKGROUND/RATIONALE:
Treatment outcomes of patients with inflammatory bowel disease (IBD) have improved enormously during the past decade due to the use of anti-tumour necrosis factor (anti-TNF) therapy. As a result, 67 to 91% of paediatric patients and 66% of adult patients is still in sustained remission two years after the initiation of anti-TNF therapy. Prolonged use of anti-TNFs comes with disadvantages such as dose dependent susceptibility to infections and dermatological adverse effects. Preliminary, mostly uncontrolled studies suggest that dose reduction by dosing interval lengthening is a realistic option in a relevant proportion of patients with IBD, provided that intensive follow-up is applied.
OBJECTIVE:
To evaluate whether a faecal calprotectin (FC) guided strategy of anti-TNF dosing interval lengthening is non-inferior in maintaining remission in patients with IBD, compared with an unchanged dosing interval.
详细描述
STUDY DESIGN:
International, multi-centre, prospective, partially randomised patient-preference trial.
STUDY POPULATION:
Study population: Eligible patients are aged 12-25 years with luminal Crohn's disease (CD) or ulcerative colitis (UC), who have three consecutive faecal calprotectin (FC) results in the target range (i.e. <250 µg/g for CD patients; <150 µg/g for UC patients) over a period of 6 months at study entry or recently confirmed endoscopic remission.
DE-ESCALATION STRATEGY:
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
入排标准
- 年龄范围
- 12 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 12-25 years
- •Diagnosed with luminal Crohn's disease or ulcerative colitis
- •Treated with either 8-weekly infliximab or 2-weekly adalimumab
- •Current anti-TNF agent as first ever anti-TNF agent or prior anti-TNF agent discontinued for reason other than primary non-response or secondary loss-of-response
- •No previous attempts to lengthen the dosing interval
- •Three consecutive faecal calprotectin (FC) results in the target range (i.e. <250 μg/g for CD patients; <150 μg/g for UC patients) in the previous 6 months or confirmed endoscopic remission within 2 months before study entry (i.e. simple endoscopic score for Crohn's disease (SES-CD) <3 points for CD patients; ulcerative colitis endoscopic index of severity (UCEIS) ≤1 point for UC patients)
- •Absence of symptoms associated with active IBD (judged by the local IBD-team)
- •Written informed consent granted
排除标准
- •Perianal fistula
- •Presence of ileostomy or ileoanal pouch (as FC cut-off is not validated for small bowel faeces)
- •Any inflammatory comorbidity, such as rheumatoid arthritis
- •Current treatment with corticosteroids (prednisone or budesonide)
- •Current pregnancy
研究组 & 干预措施
Intervention group
In patients treated with adalimumab, the dosing interval will be lengthened from 2 to 3 weeks. In patients treated with infliximab, the dosing interval will be lengthened from 8 to 12 weeks. Consists of two groups: Patients randomised to the intervention group and patients allocated to the intervention group based on preference.
干预措施: Infliximab (Biological)
Intervention group
In patients treated with adalimumab, the dosing interval will be lengthened from 2 to 3 weeks. In patients treated with infliximab, the dosing interval will be lengthened from 8 to 12 weeks. Consists of two groups: Patients randomised to the intervention group and patients allocated to the intervention group based on preference.
干预措施: Adalimumab (Biological)
结局指标
主要结局
cumulative incidence of out-of-range fecal calprotectin results at 48 weeks follow-up
时间窗: 48 weeks
Out-of-range FC results are defined as fecal calprotectin above the target range (i.e. \>250 μg/g for CD patients; \>150 μg/g for UC patients) and at least 100 μg/g increase compared with the previous result, unless the previous result was already above the target range.
次要结局
- Proportion of patients developing loss-of-response in the first 16 weeks after reverting to the previous dosing interval(Up to 48+16 weeks)
- Time to get out-of-range fecal calprotectin results(up to 48 weeks)
- Cumulative incidence of anti-TNF-associated respiratory infections and dermatological adverse effects at 48 weeks follow-up(48 weeks)
- Evolution of FC and anti-TNF trough levels in the first 16 weeks after reverting to previous dosing interval(Up to 48+16 weeks)
- Identification of predictors of successful de-escalation.(48 weeks)
研究者
P.F. van Rheenen
MD PhD
University Medical Center Groningen