Comparison of Vedolizumab Treatment to Adalimumab Dose Intensification in Crohn's Disease Patients With Loss of Response or Biomarker Activity to Adalimumab on First Line With Therapeutic Drug Concentration: A Randomized, Multicentre, Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 24
- 主要终点
- ADA optimized versus Vedolizumab as second line
研究概览
简要总结
A substantial fraction of IBD patients with an initial response to infliximab or adalimumab later experience re-emerging active disease despite ongoing anti-Tumour Necrosis Factor (TNF) agents maintenance therapy. The optimal intervention in patients with secondary loss-of-response (LOR) is still poorly defined, as there are still scant data on how best to choose the next intervention from among dose-intensification, switch to another anti-TNF or switch out of the anti-TNF class. Moreover, according to STRIDE 2 recommendations and CALM study, optimize patients based solely on lack of biological remission (CRP, calprotectin) can be discuss. If CALM study has showed that the intervention arm based on regular monitoring fecal calprotectin, CRP and/or CDAI to optimize patients under adalimumab was significantly associated to an increase rate of mucosal healing that the standard of care strategy based on only clinical activity, TDM was not available to guide drug optimization strategy.
详细描述
To address these issues, for IFX or ADA therapy, several studies have proposed some algorithms according to which interventions are based on a combined assessment of IFX or ADA drug level and antibodies-to-IFX or ADA (ATI or AAA) levels at the time of therapeutic failure. Thus, IFX or ADA levels, classified as therapeutic or sub-therapeutic, and detectable or undetectable antibodies, are used to assess if LOR is likely due to immunogenicity, to non-immune-mediated pharmacokinetic problems or due to pharmacodynamic issues, and to guide interventions accordingly.
In the last AGA recommendations, the authors suggested that in case of secondary LOR under anti TNF drug with therapeutic levels to switch to another class (such as vedolizumab). However, recent studies showed that optimization of dose regimen of the same anti-TNF in these patients may still be associated with clinical response in 25% of patients. Indeed, in a recent bicentric, retrospective and non-randomized study, the investigators showed that IBD patients under ADA maintenance therapy who experience a secondary loss of response and in whom trough levels are >4.9µg/mL, swapping to another class was significantly better than optimizing ADA, in term of time without discontinuation of 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Major patient and having given consent to participate in the study
- •Patients with Crohn's disease who have responded primary to Adalimumab princeps or similar bio with loss of response to Adalimumab (40 mg every two weeks) with therapeutically adequate levels of ADA (> 7.5 μg/mL).
- •Patient affiliated to or entitled under a social security scheme
排除标准
- •Pregnant woman
- •Patient unable to perform MRI or VCE or ileocolonoscopy or ultrasound less than one month before inclusion
- •Previous or current use of vedolizumab or ustekinumab for Crohn's disease or participation in a biological study
- •Concomitant use of immunomodulators
- •Patients on corticosteroid therapy
- •History of cancer
- •History of human immunodeficiency virus (HIV), immunodeficiency syndrome, central nervous system (CNS) demyelinating disease (including myelitis), neurological symptoms suggestive of demyelinating disease, chronic recurrent infection, active tuberculosis (received or untreated), severe infections such as sepsis and opportunistic infections
- •Patient with ileoanal pouchitis or ileorectal anastomosis
- •Patient with short small bowel syndrome as determined by investigator
- •Patients receiving total parenteral nutrition (TPN)
- •Patients receiving enteral nutrition
- •Patient under legal protection or unable to give consent
- •Hemorrhagic rectocolitis or indeterminate colitis
- •Patients treated with concomitant immunosuppressive agents
- •Patient treated with an optimized dose of adalimumab
- •Primary non-responder to Adalimumab
- •Patient previously treated with infliximab or ustekinumab before adalimumab
- •Severe relapse defined by CDAI > 330
- •Patient with anoperineal Crohn's disease
- •Crohn's disease patient with transient or permanent stoma.
研究组 & 干预措施
Adalimumab with optimisation
Patients with Crohn's disease will be included. They will have Adalimumab with optimisation as treatment.
干预措施: Adalimumab (Drug)
Vedolizumab
Patients with Crohn's disease will be included. They will have Vedolizumab as treatment.
干预措施: Vedolizumab (Drug)
结局指标
主要结局
ADA optimized versus Vedolizumab as second line
时间窗: Week 24
The primary objective will be to compare the proportion of clinical and biomarker remission (composite score) in the two groups of CD patients by 24 weeks after inclusion.
次要结局
- Proportion of endoscopic remissions according to Crohn's Disease Endoscopic Index score (CDEIS)(Week 24)
- serum C-reactive protein (CRP) mg/l(Week 24)
- Mucosal remission(Week 24)
- Clinical Decision Support Tool (CDST) score(Week 52)
- Proportion of deep remission(Weeks 0; 24)
- Proportion of clinical remission(Weeks 0; 24)
- faecal calprotectin (microG / g)(Week 24)
- Proportion of endoscopic remissions according to Lewis score(Week 24)
- Proportion of endoscopic remissions according to the number of ulcerations(Week 24)
- Proportion of endoscopic remissions according to the Magnetic Resonance Imaging (MRI) activity(Week 24)
- Proportion of endoscopic remissions according to bowel thickness(Week 24)
- Treatment failure(Weeks : 24; 52)
- Adverse events(Week 24)
- Symptomatic remission at week 24(Week 24)
- Changes in quality of life score (Inflammatory Bowel Disease Questionnaire (IBDQ)-32(Weeks : 0; 24)
- Clinical and biomarker remission(Weeks : 12; 52)
- Proportion of deep remission(Weeks 0; 24)
- Proportion of clinical remission(Weeks 0; 24)
- faecal calprotectin (microG / g)(Week 24)
- serum C-reactive protein (CRP) mg/l(Week 24)
- Proportion of endoscopic remissions according to Crohn's Disease Endoscopic Index score (CDEIS)(Week 24)
- Proportion of endoscopic remissions according to Lewis score(Week 24)
- Proportion of endoscopic remissions according to the number of ulcerations(Week 24)
- Proportion of endoscopic remissions according to the Magnetic Resonance Imaging (MRI) activity(Week 24)
- Proportion of endoscopic remissions according to bowel thickness(Week 24)
- Treatment failure(Weeks : 24; 52)
- Adverse events(Week 24)
- Symptomatic remission at week 24(Week 24)
- Changes in quality of life score (Inflammatory Bowel Disease Questionnaire (IBDQ)-32(Weeks : 0; 24)
- Clinical and biomarker remission(Weeks : 12; 52)
- Mucosal remission(Week 24)
- Clinical Decision Support Tool (CDST) score(Week 52)