Subcutaneous Vedolizumab Drug De-escalation Using Therapeutic Drug Monitoring in Inflammatory Bowel Disease: a Randomized Controlled Pilot Study
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Cost-effectiveness
研究概览
简要总结
Rationale: Subcutaneous vedolizumab is an effective maintenance therapy for patients with inflammatory bowel disease. Patients using subcutaneous vedolizumab (every 2 weeks) have higher vedolizumab serum trough concentrations than those who are treated with intravenous vedolizumab (every 4-8 weeks). Since biologic therapies such as vedolizumab are expensive, lengthening of the injection interval (de-escalation) is of interest to reduce health care costs. However, maintaining remission while extending vedolizumab injection intervals has not been evaluated yet but represents a critical component of both medical and societal costs. Studies have suggested that higher vedolizumab serum concentrations are associated with superior clinical outcomes. Our strategy is to administer subcutaneous vedolizumab with prolonged intervals using therapeutic drug monitoring, i.e. dose based on vedolizumab concentrations, to reduce medical and societal costs while preserving remission.
Objectives: To evaluate whether subcutaneous vedolizumab therapeutic drug monitoring (TDM)-guided de-escalation will be cost-effective, compared to normal dosing regimen in patients with inflammatory bowel disease in remission. The secondary objective is to investigate the efficacy of TDM-guided de-escalation subcutaneous vedolizumab dosing compared to standard dosing.
Study design: This is a single-centre, randomized controlled, open-label pilot study.
Study population: 40 patients with inflammatory bowel disease (Crohn's disease or ulcerative colitis) in steroid-free clinical and biochemical remission with subcutaneous vedolizumab maintenance therapy of 108 mg every other week for at least 6 months.
Intervention: Patients will be randomized (1:1) to the 'TDM-guided subcutaneous vedolizumab de-escalation' strategy versus 'standard care' (e.g. continuing standard subcutaneous vedolizumab dosing regimen of 108 mg every other week).
Main study parameters/endpoints: Primary endpoint: cost-effectiveness of the TDM-guided de-escalation group compared to the standard dosing group over 48 weeks. Secondary endpoints include: proportion of patients with sustained clinical remission (based on Harvey-Bradshaw Index or Simple Clinical Colitis Activity Index), proportion of patients with (sustained) biochemical remission (based on c-reactive protein and fecal calprotectin), pharmacokinetic differences (vedolizumab levels and immunogenicity), safety and quality of life (measured by SIBDQ and EQ-5D-5L).
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 Crohn's disease or ulcerative colitis
- •Clinical and biochemical remission: absence of active inflammatory intestinal symptoms, fecal calprotectin <250 ug/g and CRP <5 mg/g, HBI <5 or SCCAI <4
- •Steroid free remission for at least 6 months whilst being treated with subcutaneous vedolizumab at a stable dose of 108mg every other week.
排除标准
- •Absence of written informed consent;
- •Presence of anti-drug antibodies against vedolizumab, these levels will be determined in case the vedolizumab concentration is below 1 ug/ml;
- •Concomitant oral glucocorticosteroid usage;
- •Imminent need for IBD-related surgery as judged by the treating clinician;
- •Actively draining peri-anal fistula;
- •Patients with short bowel syndrome, an ostomy or a symptomatic stricture;
- •Active participation in another interventional trial;
- •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.
研究组 & 干预措施
Intervention
Therapeutic drug monitoring guided de-escalation
干预措施: Vedolizumab Injection (Drug)
结局指标
主要结局
Cost-effectiveness
时间窗: 48 weeks
Medical and societal expenses will be measured troughout the study. The primary outcome is at the end of the study at Week 48. Cost-effectiveness will be measured by using a cost-questionnaire developed with the health economics department, including health-related, work-related and societal costs.
次要结局
- Difference in Quality of Life(multipe times between baseline and 48 weeks)
- Biochemical parameters(multipe times between baseline and 48 weeks)
- Pharmacokinetic aspects(multipe times between baseline and 48 weeks)
- Clinical outcomes(multipe times between baseline and 48 weeks)
研究者
Geert D'Haens
Prof. dr. G.R.A.M. D'Haens
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)