Cyclic exclusive enteral nutrition versus partial enteral nutrition to maintain long-term drug-free remission in paediatric Crohn's disease (CD-HOPE): an open-label, endpoint-blinded, randomised controlled trial.

We aimed to investigate whether paediatric patients with Crohn's disease responding to nutritional induction therapy can be maintained in remission on dietary therapy without the use of medication or surgery.

我们的目标是调查对营养诱导治疗有反应的克罗恩病儿童患者是否可以在不使用药物或手术的情况下，通过饮食治疗维持缓解。

Methods

In this open-label, endpoint-blinded, randomised controlled trial(CD-HOPE) done in 21 hospitals of the GETAID pédiatrique network in France, eligible patients were aged 6 years to younger than 18 years with Crohn's disease (newly diagnosed or relapsing after drug treatment) who had reached clinical remission (weighted Paediatric Crohn's Disease Activity Index [wPCDAI] ≤12·5) after induction therapy with 6-12 weeks of exclusive enteral nutrition (EEN; 100% of calories).

在这项开放标签、终点盲法、随机对照试验（CD-HOPE）中，研究在法国GETAID pédiatrique网络的21家医院进行，符合条件的患者年龄在6岁至18岁以下，患有克罗恩病（新诊断或药物治疗后复发），在经过6-12周的全肠外营养（EEN；占总热量的100%）诱导治疗后，达到了临床缓解（加权儿童克罗恩病活动指数[wPCDAI] ≤12·5）状态。

Stratified by age (≤10 years or >10 years) and relapse status, patients were randomly assigned (1:1) using block randomisation to receive either cyclic EEN (C-EEN; 100% of daily caloric requirements) for 2 weeks every 8 weeks for at least six cycles or daily partial enteral nutrition (PEN; 25% of daily caloric requirements) for 52 weeks.

根据年龄（≤10岁或>10岁）和复发状态进行分层，患者使用区块随机化以1:1的比例被随机分配，接受循环全肠外营养（C-EEN；占每日热量需求的100%）每8周2周，至少六个周期，或每日部分肠外营养（PEN；占每日热量需求的25%）52周。

Oral MODULEN IBD was used for both.

口服MODULEN IBD被用于两者。

Except for the 2-week intervals of EEN in the C-EEN group, food access was not restricted.

除了C-EEN组中EEN的2周间隔外，食物摄入并未受到限制。

The primary endpoint was relapse rate at 12 months.

主要终点是12个月时的复发率。

A relapse was defined as: (1) a wPCDAI score greater than 12·5 at two successive visits, or (2) a wPCDAI greater than 12·5 once and the need for Crohn's disease-related surgery, medication, or study exit, or (3) a wPCDAI score continuously greater than 12·5 since the last study visit, or (4) incomplete wPCDAI and moderate or severe Physician Global Assessment at any timepoint.

复发定义为：(1)连续两次访问的wPCDAI评分大于12.5，或(2)一次wPCDAI评分大于12.5且需要克罗恩病相关手术、药物治疗或研究退出，或(3)自上次研究访问以来wPCDAI评分持续大于12.5，或(4)任何时候wPCDAI不完整且中度或重度的医师总体评估。

Primary and safety analyses were performed on an intention-to-treatbasis.

主要疗效和安全性分析是基于意向治疗原则进行的。

This trial was registered on ClinicalTrials.gov (NCT02201693) and is complete.

该试验已在ClinicalTrials.gov上注册（NCT02201693），并已完成。

Results

Between Dec 12, 2014, and Sept 4, 2018 (last patient visit Oct 2, 2019), 112 patients were screened and 100 patients (70 boys and 30 girls) were randomly assigned to C-EEN (n=49) or PEN (n=51).

2014年12月12日至2018年9月4日（最后一名患者访问日期为2019年10月2日），对112名患者进行了筛查，其中100名患者（70名男孩和30名女孩）被随机分配到C-EEN组（n=49）或PEN组（n=51）。

Median age of participants was 12 years (IQR 11-13) in the C-EEN group and 13 years (11-14) in the PEN group.

C-EEN组的参与者中位年龄为12岁（四分位数间距11-13岁），PEN组的中位年龄为13岁（四分位数间距11-14岁）。

At 12 months, 24 (49%) of 49 patients had relapsed on C-EEN compared with 39 (76%) of 51 patients on PEN (adjusted odds ratio 0·29 [95% CI 0·13-0·70], p=0·0051). 19 adverse events occurred in 17 patients: four serious adverse events in four patients on PEN, not related to treatment, and 15 non-serious adverse events in 13 patients (nine in seven patients on C-EEN and six in six patients on PEN).

在12个月时，49名患者中有24名（49%）在C-EEN治疗下复发，而51名患者中有39名（76%）在PEN治疗下复发（调整后的优势比为0.29 [95%置信区间0.13-0.70]，p=0.0051）。共有17名患者发生了19起不良事件：PEN组中有4名患者发生了4起严重不良事件，与治疗无关；C-EEN组中有7名患者发生了9起非严重不良事件，PEN组中有6名患者发生了6起非严重不良事件。

The serious adverse events were all related to Crohn's disease relapse requiring hospitalisation for rescue therapy.

所有严重不良事件均与克罗恩病复发有关，需要住院进行紧急治疗。

Six adverse events were possibly related to study treatment: one patient in the C-EEN group reported transient vomiting and diarrhoea at the start of the first EEN cycle, one patient in the C-EEN group developed anorexia and, in the PEN group, four patients reported either weight loss, nausea, Crohn's disease relapse, or skin infection.

六种不良事件可能与研究治疗有关：在C-EEN组中，一名患者在第一次EEN周期开始时报告了短暂的呕吐和腹泻，另一名C-EEN组的患者出现了厌食症，而在PEN组中，四名患者报告了体重减轻、恶心、克罗恩病复发或皮肤感染。

No malignancy or death was reported in this study.

本研究中没有报告任何恶性肿瘤或死亡事件。

interpretation

C-EEN was superior to PEN in maintaining clinical remission over 1 year in paediatric patients with Crohn's disease responding to EEN induction therapy.

C-EEN 在维持接受 EEN 诱导治疗后对克罗恩病有反应的儿童患者 1 年以上的临床缓解方面优于 PEN。

These findings suggest a new way to use nutritional therapy for maintaining drug-free long-term remission in patients with Crohn's disease who are responding to EEN induction therapy.

这些发现提示了一种新的营养治疗方式，用于维持对 EEN 诱导治疗有反应的克罗恩病患者在无药物情况下的长期缓解。

funding

Assistance Publique-Hôpitaux de Paris and Nestlé Health Science.

巴黎公立医院联合Nestlé Health Science。