Discontinuation of Infliximab Therapy in Patients With Crohn's Disease During Sustained Complete Remission: A Multi-center, Double Blinded, Randomized, Placebo Controlled Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 115
- 试验地点
- 13
- 主要终点
- Time to relapse after discontinuation of IFX
研究概览
简要总结
The purpose of this study is to determine whether infliximab can favourably and safely be discontinued in patients with Crohn's disease in sustained complete clinical, biochemical, and endoscopic remission on infliximab.
Further to examine the clinical utility of measuring levels/activity of infliximab and activity of anti-infliximab Ab in patients in sustained complete remission, in order to investigate whether pharmacoimmunological data can predict the clinical outcome and rationalize therapeutic management of these patients with respect to continuation or discontinuation of infliximab therapy. Additional, to investigate the optimal time-point, out of three, to measure this activity.
详细描述
Recent guidelines for the management of Crohn's disease conclude that currently available data are insufficient to make firm recommendations on when and in whom to stop TNF-α antibody (TNF-α Ab) treatment after having obtained clinical remission. Further, the term "remission" is not well uniformly defined and may incorporate one or more features such as clinical remission, as assessed by CDAI, biochemical remission, endoscopical remission etc. The recently published prospective STORI study of 115 patients with luminal Crohn's disease reported that 56% of patients with Crohn's disease who had discontinued infliximab (IFX) while in clinical remission, maintained remission one year after discontinuation of therapy. Predictors of relapse included certain clinical features as well as objective biochemical and endoscopical markers of disease activity. Consistent with these data, we have recently reported that 61% of our own patients with Crohn's disease, who discontinued IFX while in complete clinical, steroid free IFX induced remission, maintained remission after one year; and half the patients were still in remission after nearly two years (median 680 days [412-948]).
A prospective randomized study of patients with Crohn's disease is necessary to confirm and extend the limited findings above, and assess whether IFX can be safely discontinued in a selected subgroup of patients with complete clinical, biochemical, and endoscopical remission.
Methods:
Study design: Prospective, double-blinded, randomized, placebo-controlled, Danish multi-center study with estimated seven Danish participating centers. Patients and treating physicians are blinded for the type of intervention.
Study population: Patients with luminal Crohn's disease in sustained complete remission on IFX.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Luminal Crohn's disease defined according to standardized diagnostic criteria.
- •Age ≥ 18 years.
- •IFX induction treatment week 0, 2, 6 followed by maintenance therapy.
- •IFX treatment length minimum 12 months. Episodic therapy with IFX pause > 12 weeks is not accepted within the last year. The treatment interval in the last three months has to be of 6-10 weeks.
- •Complete remission defined as:
- •CDAI score < 150 and
- •Biochemical remission, and
- •No other signs of disease activity as evaluated by endoscopic examination or by magnetic resonance imaging (MRI).
- •Stable remission, judged by the treating physician, at two consecutive treatments visits corresponding 2 scheduled IFX infusions. Thus, the first visit is during IFX maintaining therapy (screening visit). The second visit is at time of inclusion corresponding time of next scheduled IFX infusion (i.e. after ≈ 8 weeks).
- •No use of oral steroids within 3 months prior to inclusion.
- •Concomitant therapy with other immune suppressants, except steroids, is allowed. The dosage and frequency must have been stable three months prior to inclusion and must remain stable throughout the study period.
排除标准
- •Initial indication for IFX being predominantly fistulizing perianal disease.
- •Any contraindications for continuing IFX treatment, including prior acute or delayed infusion reaction to a TNF- inhibiting agent, any active infection requiring parenteral or oral antibiotic treatment, known infection with tuberculosis, human immunodeficiency virus (HIV) or hepatitis virus.
- •Any condition including physician finds incompatible with participation in the study or the patient being unwilling or unable to follow protocol requirements.
研究组 & 干预措施
infliximab
Patients in this arm are randomized to continue IFX therapy at an unchanged dosage and frequency.
干预措施: Infliximab (Drug)
Placebo
Patients in this arm are randomized to receive matching placebo.
干预措施: Placebo (Other)
结局指标
主要结局
Time to relapse after discontinuation of IFX
时间窗: 48 weeks
Relapse defined as CDAI \>150 and an increase in CDAI from baseline \>70 over 2 consecutive weeks (or definitive relapse as judged by treating physician)
次要结局
- Time to loss of remission(48 weeks)
- Proportion of patients who maintain clinical remission(48 weeks)
- Proportion of patients who maintain clinical and endoscopic remission(48 weeks)
- Proportion of patients who experience relapse (more stringent definition)(48 weeks)
- Proportion of patients who experience relapse(48 weeks)
研究者
Forskningsenheden
Mark Ainsworth, MD, professor
Odense University Hospital