Y-ECCO Literature Review: Homira Ayubi

Nutritional therapy in the form of exclusive enteral nutrition (EEN) may be one option. EEN provides 100% of a person’s nutritional requirement in the form of a liquid formula, and it is thought to act through systemic and local immune modulation, inducing mucosal healing, altering intestinal flora and achieving clinical remission. In children with Crohn’s Disease who are receiving EEN, the rate of mucosal healing has been reported to be as high as 75% as compared with 33% in those treated with corticosteroids alone. Therefore, EEN is recommended as first-line therapy in children with Crohn’s Disease [3–5]. It has also been shown to be effective in adults with Crohn’s Disease [6].

It was previously thought that disease location is linked with the efficacy of EEN, with previous studies suggesting that best results are achieved in those with small bowel disease. However, a recent meta-analysis has shown that treatment response to EEN is unrelated to Crohn’s phenotype [7].

Sahu et al. hypothesised that addition of EEN to corticosteroid therapy in ASUC will improve the response rate to intravenous corticosteroids and reduce the need for rescue therapy.

Methods

This was a single-centre, open-label, randomised controlled trial. Patients with ASUC as defined by Truelove and Witts’ criteria were randomised to receive EEN or standard of care (SOC). Patients in the EEN group were given 7 days of EEN (Peptamen) with standard medical care, while those in the SOC group received normal diet with standard medical care. Standard medical care consisted of intravenous hydrocortisone (400 mg/day), continuation of oral and topical 5-ASA, hydrocortisone enemas and venous thromboprophylaxis.

The primary outcome was to measure the proportion of patients with corticosteroid failure defined as the need for medical rescue therapy or colectomy. Changes in inflammatory markers (faecal calprotectin, C-reactive protein, serum albumin), numbers requiring colectomy during index hospital admission, treatment-related adverse events and response to medical rescue therapy were measured as secondary outcomes.  Patients who were followed up for a further 6 months were compared for colectomy rates and hospitalisation for disease flare and a composite of both outcomes.

Key findings

Sixty-two of the 75 patients were randomised to receive either EEN (n=32) or SOC (n=30). Five patients in the EEN group could not tolerate the feed; hence they were removed from per protocol analysis but were included in the intention-to-treat analysis.

Treatment outcome

In the per protocol analysis, there was a significantly lower rate of corticosteroid failure in the EEN group compared with the SOC group (19% vs 43%; p=0.04).  Median length of hospitalisation was shorter in the EEN group than in the SOC group.

No difference in colectomy rate or response to medical rescue therapy was seen between the groups in either type of analysis.

Inflammatory markers and biochemical parameters

Patients in the EEN group had a higher serum albumin level at day 7 (34±4 g/L vs 29±3 g/L; p<0.01). Median day 5 CRP was lower in the EEN group than in the SOC group [5.7 (1.1–39.3) mg/L vs 11.7 (4.3–55.4) mg/L]. Patients in the EEN group had a greater reduction in CRP [delta CRP 23.4 (6.8–38.9) vs 11.4 (1.9–25); p=0.04) compared with the SOC group. On day 3, patients on EEN had a greater reduction in faecal calprotectin (FCP) compared with the SOC [delta FCP 315 (129–797) µg/g vs 140(-386 to 459) µg/g, p=0.04).

Long-term outcome

Twenty-five patients in the EEN group and 23 patients in the SOC group were followed up for more than 6 months for colectomy and repeat hospitalisation rates. Patients in the EEN group had a significantly lower composite outcome of both rates compared with the SOC group (16% vs 39%; p=0.045).

Conclusion

Data on the use of EEN in adults with IBD is less robust as EEN is mainly used as first-line therapy for children with Crohn’s Disease [4]. However, this study shows that EEN can be effective in adults, irrespective of the site and type of IBD.

The two groups in this study were similar to each other at baseline with respect to the Truelove and Witts’ criteria score, CRP, FCP and endoscopic disease severity score, a factor which can affect response to corticosteroids. However, failure to respond to corticosteroids, defined as the need for medical rescue therapy or colectomy, was significantly less likely in the EEN group than in the SOC group (19% vs 43%; p=0.04). The significant improvement in inflammatory markers such as CRP, FCP and serum albumin is indicative of the anti-inflammatory effects of EEN [4]. The composite outcome for colectomy and repeat hospitalisation for disease flare greater than 6 months following index hospital admission was lower in the EEN group than in the SOC group, which the authors propose is due to the sustained effect of EEN and possibly a change in the microbiota. In children treated with EEN, an abundance of Erysipelotrichaceae has been described in a randomised controlled trial and a reduction in Erysipelotrichaceae has been linked with increased inflammation in IBD [6,7].

The relatively small sample size of this study is one of its limitations, recruitment being terminated early due to the coronavirus pandemic. It was also a single-centre study. However, it generated intriguing results that deserve external validation in future larger-scale, multicentre studies.

References

1. Dinesen LC, Walsh AJ, Protic MN, et al. The pattern and outcome of acute severe colitis. J Crohns Colitis. 2010;4:431–7.
2. Turner D, Walsh CM, Steinhart AH, Griffiths AM. Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression. Clin Gastroenterol Hepatol. 2007;5:103–10.
3. Zachos M, Tondeur M, Griffiths AM. Enteral nutritional therapy for induction of remission in Crohn’s disease. Cochrane Database Syst Rev. 2007;(1):CD000542
4. Ruemmele FM, Veres G, Kolho KL, et al. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease. J Crohns Colitis. 2014;8:1179–207.
5. Borrelli O, Cordischi L, Cirulli M et al. Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn's disease: a randomized controlled open-label trial. Clin Gastroenterol Hepatol. 2006;4:744–
6. Levine A, Wine E, Assa A, et al. Crohn's disease exclusion diet and partial enteral nutrition induces sustained remission in a randomized controlled trial. Gastroenterology. 2019;157:440–50.
7. Gevers D, Kugathasan S, Denson L, et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe. 2014;15:382–92.

Homira Ayubi - Short Biography

Homira Ayubi is a gastroenterology registrar who is currently in her third year of training at Guy's and St Thomas' Hospital in London. Her areas of interest are IBD and endoscopy.