Yanai Henit, Levine Arie, Hirsch Ayal, Boneh Rotem Sigall, Kopylov Uri, Eran Hagar Banai, Cohen Nathaniel A, Ron Yulia, Goren Idan, Leibovitzh Haim, Wardi Joram, Zittan Eran, Ziv-Baran Tomer, Abramas Lee, Fliss-Isakov Naomi, Raykhel Barbara, Gik Tamar Pfeffer, Dotan Iris, Maharshak Nitsan
Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Paediatric Gastroenterology Unit, Wolfson Medical Center, Holon, Israel.
Lancet Gastroenterol Hepatol. 2022 Jan;7(1):49-59. doi: 10.1016/S2468-1253(21)00299-5. Epub 2021 Nov 2.
The Crohn's disease exclusion diet (CDED) with partial enteral nutrition is effective for induction of remission in children with mild-to-moderate Crohn's disease. We aimed to assess the CDED in adults with Crohn's disease.
We did an open-label, pilot randomised trial at three medical centres in Israel. Eligible patients were biologic naive adults aged 18-55 years with mild-to-moderate Crohn's disease (defined by a Harvey-Bradshaw Index score of 5-14 points), a maximal disease duration of 5 years, with active disease on colonoscopy, or imaging with elevated inflammatory markers (C-reactive protein >5 mg/L or faecal calprotectin concentration >200 μ/g). Patients were randomly assigned (1:1) to CDED plus partial enteral nutrition or CDED alone for 24 weeks. Randomisation was via block randomisation (block sizes of six) using sealed, numbered, and opaque envelopes. Patients and investigators were aware of which group patients were assigned to due to the nature of the different interventions. The primary endpoint was clinical remission, defined as a Harvey-Bradshaw Index score of less than 5 at week 6. The primary endpoint was assessed in the intention-to-treat (ITT) population, which included all patients who used the dietary therapy for at least 48 h. We report results of the final analysis. This trial is registered with ClinicalTrials.gov, NCT02231814.
Between Jan 12, 2017, and May 11, 2020, 91 patients were screened, of whom 44 were randomly assigned to the CDED plus partial enteral nutrition group (n=20) or CDED alone group (n=24). 19 patients in the CDED plus partial enteral nutrition group and 21 patients in the CDED alone group received the allocated intervention for at least 48 h and thus were included in the ITT analysis. At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618). Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group). 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group). No serious adverse events or treatment-related adverse events were reported in either group.
CDED with or without partial enteral nutrition was effective for induction and maintenance of remission in adults with mild-to-moderate biologic naive Crohn's disease and might lead to endoscopic remission. These data suggest that CDED could be used for mild-to-moderate active Crohn's disease and should be assessed in a powered randomised controlled trial.
Azrieli Foundation and Nestle Health Science.
克罗恩病排除饮食（CDED）联合部分肠内营养对轻至中度克罗恩病患儿诱导缓解有效。我们旨在评估CDED对成年克罗恩病患者的效果。
我们在以色列的三个医学中心进行了一项开放标签的试点随机试验。符合条件的患者为18 - 55岁、未使用过生物制剂的轻至中度克罗恩病成年患者（根据哈维 - 布拉德肖指数评分5 - 14分定义），疾病最长持续时间为5年，结肠镜检查显示疾病活动，或影像学检查显示炎症标志物升高（C反应蛋白>5 mg/L或粪便钙卫蛋白浓度>200 μg/g）。患者被随机分配（1:1）至CDED联合部分肠内营养组或单纯CDED组，为期24周。随机分组通过使用密封、编号且不透明的信封进行区组随机化（区组大小为6）。由于不同干预措施的性质，患者和研究人员知晓患者被分配至哪一组。主要终点为临床缓解，定义为第6周时哈维 - 布拉德肖指数评分小于5分。主要终点在意向性分析（ITT）人群中进行评估，该人群包括所有接受饮食治疗至少48小时的患者。我们报告最终分析结果。本试验已在ClinicalTrials.gov注册，注册号为NCT02231814。
在2017年1月12日至2020年5月11日期间，共筛查了91例患者，其中44例被随机分配至CDED联合部分肠内营养组（n = 20）或单纯CDED组（n = 24）。CDED联合部分肠内营养组的19例患者和单纯CDED组的21例患者接受了分配的干预至少48小时，因此被纳入ITT分析。在第6周时，CDED联合部分肠内营养组中的19例患者中有13例（68%）、CDED组中的21例患者中有12例（57%）实现了临床缓解（p = 0.4618）。在第6周时缓解的25例患者中，20例（80%）在第24周时持续缓解（CDED联合部分肠内营养组12例，单纯CDED组8例）。40例患者中有14例（35%）在第24周时达到内镜缓解（CDED联合部分肠内营养组8例，单纯CDED组6例）。两组均未报告严重不良事件或与治疗相关的不良事件。
CDED联合或不联合部分肠内营养对未使用过生物制剂的轻至中度成年克罗恩病患者诱导和维持缓解有效，且可能导致内镜缓解。这些数据表明CDED可用于轻至中度活动性克罗恩病，应在一项有足够样本量的随机对照试验中进行评估。
阿兹列里基金会和雀巢健康科学公司。
