Control Crohn Safe With Episodic Adalimumab Monotherapy as First Line Treatment Study.
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 158
- 试验地点
- 6
- 主要终点
- Number of yearly-quarters of corticosteroid free remission as a measure of treatment efficacy
研究概览
简要总结
Crohn's disease (CD) is a chronic disease with a heterogeneous clinical presentation, relapse rate and treatment response. Insufficient control of mucosal inflammation results in irreversible bowel damage and complications and at present no markers are available to predict such a complicated disease course at diagnosis. Therefore, to prevent overtreatment of low risk patients, step-up treatment with subsequent introduction of corticosteroids, thiopurines maintenance and TNF-blockers if a previous category fails is standard care. Combination treatment with thiopurines and a TNF-blocker is more effective than monotherapy but associated with a higher risk for infectious complications. Landmark studies convincingly showed an improved long-term outcome if the TNF-blocker infliximab is introduced early after diagnosis. The standard step-care approach thus prolongs steroid exposure and delays start of disease modifying biologicals in high risks patients. Given the higher efficacy of combination therapy with a thiopurine of infliximab and potential allergic reactions and lower response rates after re-initiation of this chimeric biological, temporary monotherapy with this TNF-blocker has not been studied as first line treatment before. Adalimumab is a humanised monoclonal antibody and subsequently, combination therapy of adalimumab + thiopurines has only a marginal effect on anti-drug anti-body formation. Furthermore, combination therapy with adalimumab does not enhance the clinical response. Therefore, periodic treatment with adalimumab in combination with close monitoring after drug-discontinuation, in newly diagnosed CD might improve outcome, reduce drug-related side effects while still preventing overtreatment.
The aim of this study is to compare the long-term efficacy and safety of periodic adalimumab as initial treatment in newly diagnosed CD patients compared to standard step-care with corticosteroid/budesonide as the initial treatment
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed CD patients or CD patients with a flare, visiting the outpatient clinic or endoscopy ward of the participating centres
- •CD diagnosis according to ECCO-guidelines + complete ileo-colonoscopy + complete small bowel imaging at diagnosis (MRI or CT-enterography )
- •Naïve to biologicals
- •Sufficient knowledge of Dutch language
- •18 years old ≤ 70 years old
- •Smartphone with internet access
- •Use of myIBDcoach or willingness to start using myIBDcoach
排除标准
- •Use of prednisone for longer than 4 weeks in the year before screening
- •Use of budesonide (≥6 mg daily) for a duration longer than 3 months in the year before screening
- •Use of thiopurines in the 3 years before screening
- •Indication for primary treatment with biologicals or surgery
- •Malignancy in 5 years before treatment. Exception is adequately treated non-melanoma skin cancer
- •Contra-indication for TNF-blockers or immunosuppressive agents
- •Contra-indication for MRI- and CT-enterography
- •Patients with short bowel syndrome or an ostomy
研究组 & 干预措施
Adalimumab
Episodic adalimumab monotherapy as first line treatment for 6 months
干预措施: Adalimumab (Drug)
Standard step-up care
Step-up care as first line treatment, starting with corticosteroids.
干预措施: standard step-up care (Drug)
结局指标
主要结局
Number of yearly-quarters of corticosteroid free remission as a measure of treatment efficacy
时间窗: at week 96
Remission is defined as combined clinical (MIAH scores (≤3)) and biochemical (C-reactive protein ≤5 mg/L (i.e. within normal range) and fecal calprotectin ≤ 200 μg/g) remission.
次要结局
- Incidence of serious disease related adverse events(at week 24, 48 and 96)
- Integer amount of direct health care costs (in €)(at week 96)
- Integer amount of indirect health care costs (in €)(at week 96)
- Cumulative structural bowel damage as a measure of disease progression(at week 96)
- Incidence of drug related serious adverse events(at week 24, 48 and 96)
- Quality of life as assessed by QoL EQ-5D-5L questionnaire(at week 24, 48 and 96)
- Endoscopic remission as assessed by SES-CD(at week 24)
- Time to remission(at week 96)
- Corticosteroid use(at week 24, 48 and 96)