The Optimum Length of Enteral Nutritional Therapy for Induction of Remission in Paediatric Crohn's Disease: A Randomised Controlled Feasibility Trial

Abstract

BACKGROUND: Liquid diets were first used in Crohn's disease (CD) to provide preoperative nutritional support, but many of these patients unexpectedly went into remission before operation. Subsequent studies have confirmed the efficacy of enteral nutrition for induction of remission in children with CD and this is first line therapy with the UK. The length of treatment varies in the published paediatric studies from 3 to 10 weeks, with treatment continuing to scheduled end regardless of remission status. The use of exclusive enteral nutrition can avoid exposure to corticosteroids and associated side effects, but lengthy treatment courses may be daunting and affect adherence. No study has investigated the impact of the length of treatment in children on remission or relapse rates. Our aim was to complete a randomised controlled feasibility trial investigating whether the length of treatment with enteral nutrition in paediatric patients impacts on remission rates and withdrawal from therapy.

METHODS: The study was completed in Royal Manchester Children's Hospital, a tertiary paediatric unit within the UK with approximately 400 children diagnosed with IBD. Patients aged 8 to 17 years with a diagnosis of CD were considered for inclusion. Exclusion criteria included: Gastrostomy in situ, Severe CD requiring corticosteroids or surgery, treatment with other therapies within 12 weeks prior to randomisation or anti-TNF agents within the last 6 weeks prior to randomisation. Consent was obtained and baseline characteristics collected. Patients were randomised by a concealed, third-party process. Regimens were of 4, 6, 7, 8, and 10 weeks exclusive polymeric enteral nutrition, with predetermined formulations. Outcomes assessed at baseline and 10 weeks included disease activity, health related quality of life, adverse events and withdrawal rates.

RESULTS: Thirty-eight patients with flare ups of CD were considered to start polymeric diet within the study period. Twenty-seven were eligible for inclusion and 12 consented for inclusion (Randomised length of therapy 4 Weeks n = 3, 6 weeks n = 3, 7 weeks n = 2, 8 weeks n = 3, 10 weeks n = 1). The most cited reason for not consenting for inclusion were that 10 weeks was too long for therapy (n = 6) and 4 weeks too short (n = 4). All patients who received exclusive enteral nutrition had gained weight at 4 week review (Mean = 4.4 kg) and final 10 week review (Mean = 7.1 kg). There was no difference in rates of remission between patients treated with 4, 6, or 7 weeks therapy. No patients completed 8 or 10 weeks diet. No significant adverse events were encountered. Withdrawal rates were 63% with reasons including lost to follow up (n = 4), need for steroids (n = 2) and patient not willing to stop therapy at predetermined time (n = 1).

CONCLUSIONS: This is the first randomised controlled trial investigating the impact of the enteral nutritional therapy for induction of remission in Paediatric Crohn's disease. This feasibility trial has demonstrated the safety of all lengths of therapy, as well as supporting the possible equivalent efficacy of shorter lengths of therapy. A full randomised controlled trial is warranted to investigate further. Difficulties highlighted in this feasibility trial can inform future study design and will be highlighted in detail.