Cyclic enteral nutrition studied for maintaining paediatric Crohn's remission

Evidence before this study

Nutritional therapy in the form of exclusive enteral nutrition (EEN) is recommended by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organisation as first-line induction therapy in children with active, mild-to-moderate, luminal Crohn's disease. Many studies and subsequent meta-analyses have confirmed its rapid and profound anti-inflammatory effect, with clinical remission rates of up to 60–80% on sole nutritional induction therapy and mucosal healing rates of 50% or more. However, after a first course of nutritional therapy, many patients receive medical therapy to maintain remission over time. We performed a literature search of MEDLINE and Web of Science from database inception to January, 2014, with an update to March 31, 2025, for clinical trials investigating the maintenance of remission in patients with Crohn's disease with nutritional therapy. Search terms included “inflammatory bowel diseases”, “Crohn's disease”, “pediatric”, “nutrition”, “maintenance therapy”, and “longterm remission”. No randomised controlled trials (RCTs) have addressed the question of whether nutritional therapy alone without added immunomodulators is efficacious in maintaining remission for up to 12 months in children and adolescents with Crohn's disease. Some data indicate that the addition of nutritional therapy to ongoing medical therapy or after surgical resection could increase remission rates at 6 or 12 months in adult patients with inflammatory bowel disease. One paediatric clinical trial showed that a 2-week course of EEN followed by the Crohn's disease exclusion diet and partial enteral nutrition (PEN) was able to maintain 18 (60%) of 30 patients in clinical remission for up to 24 weeks, with 75% of patients starting immunomodulators during the trial. In addition, no clinical or biological biomarkers exist that predict long-term response to nutritional maintenance therapy.

Added value of this study

To the best of our knowledge, this is the first RCT showing that standalone nutritional maintenance therapy (without the addition of immunomodulators) in the form of cyclic EEN (C-EEN) was able to maintain clinical remission in 25 (51%) of 49 paediatric patients with Crohn's disease over 12 months (vs 12 [24%] of 51 on PEN). As it is difficult to follow and adhere to prolonged nutritional therapy in the form of extreme food restriction (eg, to one liquid source of food), or in the form of a restrictive diet, the cyclic schedule of EEN used in this RCT (6 weeks of unrestricted food and 2 weeks of EEN) offers a feasible alternative. The microbial analyses suggested a specific pattern (high levels of Enterobacter) that predicts poor response to nutritional maintenance therapy.

Implications of all the available evidence

The findings of this RCT indicate that a select group of paediatric patients with Crohn's disease could be maintained in remission over 12 months without using immunosuppressors or biologics. Based on these findings, maintenance nutritional therapy in the form of C-EEN should be considered a treatment strategy for children and adolescents with mild-to-moderate Crohn's disease. These findings could also be extended to adult patients with Crohn's disease. The finding of a microbial pattern predictive of response to nutritional maintenance therapy requires confirmation in independent cohorts.

Source: The Lancet Gastroenterology & Hepatology