Lengthening Adalimumab Dosing Interval in Quiescent Crohn's Disease Patients
试验速览
- 阶段
- 4 期
- 入组人数
- 174
- 试验地点
- 31
- 主要终点
- Cumulative incidence of persistent disease flares.
研究概览
简要总结
Crohn's disease is a chronic inflammatory bowel disease. This disease can be treated with, among other things, biologicals such as adalimumab. Patients use adalimumab for a long time to maintain remission and to prevent relapse of the bowel inflammation. The disadvantages of this therapy are the high price and side effects (such as the higher risk of infection).
Currently, adalimumab is given every 2 weeks, by injection under the skin. The optimal time between two injections has never been investigated before. Prior research in patients with rheumatoid arthritis shows that disease remission can be maintained with longer injection-intervals. Our hypothesis is that this is the same for Crohn's disease patients. Our aim is to show non-inferiority of extending the adalimumab dosing interval, under strict disease monitoring in Crohn's disease patients in sustained (>9 months) clinical remission, compared to standard care.
During the trial,174 patients with stable Crohn's disease will be divided into 2 groups. One group continues adalimumab injections with the same 2-week interval. And the other group will incrementally extend the interval to 4 weeks, under strict disease monitoring. If a step-down leads to recurrence of disease activity patients will return to the preceding effective dosing interval. Thus, we will investigate whether, and for whom, it is safe to extend the adalimumab injection interval.
详细描述
Rationale
Adalimumab is both an effective induction and maintenance therapy for Crohn's disease (CD). Due to the risk of side effects (infections, injection reaction) and high costs, an extension of the injection interval is an attractive option. However, this strategy has not been evaluated yet in a randomized controlled trial in CD patients.
Objective
To assess non-inferiority and cost-effectiveness of disease activity guided adalimumab interval lengthening in CD patients in sustained (>9 months) clinical remission, compared to standard dosing of every other week.
Study design
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of colonic and/or distal ileal CD
- •Sustained steroid-free clinical remission for >9 months whilst being treated with adalimumab at a stable dose
- •Adalimumab dosed at 40 mg sc every 2 weeks
- •Full clinical response and disease control, all three criteria below need to be fulfilled prior to enrollment:
- •Absence of active inflammatory intestinal or extra-intestinal symptoms, as judged by both patient and physician
- •Fecal calprotectin (FC) < 150 μg/g and C reactive protein (CRP) <10 mg/L
- •Harvey Bradshaw Index (HBI) <5
排除标准
- •Absence of written informed consent
- •Concomitant corticosteroid usage
- •Need for CD-related surgery
- •Actively draining peri-anal fistula
- •Pregnancy or lactation
- •Other significant medical conditions that might interfere with this study (such as current/recent malignancy, immunodeficiency syndromes and psychiatric illness)
- •Impossibility to measure outcomes, e.g. planned relocation, language issues, short life expectancy
结局指标
主要结局
Cumulative incidence of persistent disease flares.
时间窗: From the date of randomization up to week 48.
A persistent flare is defined as two of three of the following criteria persisting for \> 8 weeks, despite dose escalation of adalimumab; FC \>250 µg/g, CRP≥10 mg/L, HBI ≥5. Non-inferiority is reached if the difference in cumulative incidence of persistent flares not exceeds the non-inferiority margin of 15%.
次要结局
- Cumulative incidence of transient disease flares.(From the date of randomization up to week 48.)
- Whether adalimumab drug level is associated with successful interval lengthening(From the date of randomization up to week 48.)
- Whether biochemic FC or CRP are associated with successful interval lengthening(From the date of randomization up to week 48.)
- The decremental cost effectiveness ratio of this interval lengthening strategy(From the date of randomization up to week 48.)
- (Serious) adverse event rate(From the date of randomization up to week 48.)
- Whether co-medication use is associated with successful interval lengthening(From the date of randomization up to week 48.)