A nomogram for predicting the response to exclusive enteral nutrition in adult patients with isolated colonic Crohn’s disease

Background: Isolated colonic Crohn’s disease (cCD) responds less well to induction therapy with exclusive enteral nutrition (EEN) compared with ileal or ileocolonic disease in adult patients; therefore, we aimed to identify the factors that influence the response to EEN and develop a predictive nomogram model to optimize the use of EEN in cCD patients. Materials and methods: Eighty-five cCD patients treated with EEN as first-line therapy at our center between 1 June 2012 and 30 June 2018 were retrospectively analyzed as the primary cohort. The primary endpoint was clinical remission after EEN therapy. Potential predictive factors for the efficacy of EEN were assessed by univariate and multivariate analyses, and a nomogram to predict the response to EEN therapy in cCD patients was designed. Another 19 cCD patients were retrospectively included in the validation cohort to verify the accuracy of the nomogram model. Results: The clinical remission rates for the primary cohort and validation cohort were 52.9% and 47.4%, respectively. Pancolitis was the greatest contributor to the risk of failure to respond to EEN [odds ratio (OR) = 4.896; 95% confidence interval (CI) = 1.223–19.607; p = 0.025], lean body mass index (LBMI), colonic lesion features, simple endoscopic scores for Crohn’s disease, C-reactive protein before treatment and ∆prealbumin were also related to the efficacy of EEN in cCD. The nomogram model showed robust discrimination, with an area under the receiving operating characteristic curve of 0.906. Conclusion: Several predictive factors for response to EEN therapy in cCD adult patients were identified, and a promising nomogram that can predict the effect of EEN in cCD was developed.

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The use of exclusive enteral nutrition for induction of remission in children with Crohn’s disease demonstrates that disease phenotype does not influence clinical remission

Alimentary Pharmacology & Therapeutics ◽

10.1111/j.1365-2036.2009.04067.x ◽

2009 ◽

Vol 30 (5) ◽

pp. 501-507 ◽

Cited By ~ 95

Author(s):

E. BUCHANAN ◽

W. W. GAUNT ◽

T. CARDIGAN ◽

V. GARRICK ◽

P. MCGROGAN ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Enteral Nutrition ◽

Clinical Remission ◽

Disease Phenotype ◽

Exclusive Enteral Nutrition

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P606 Exclusive enteral nutrition with a polymeric diet is efficacious in inducing remission in adults with active Crohn’s disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.734 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S505-S508

Author(s):

P Kakkadasam Ramaswamy ◽

R Mutsekwa ◽

X Lan ◽

Y Chen ◽

R Angus ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Enteral Nutrition ◽

Induction Therapy ◽

Final Analysis ◽

Adult Patients ◽

Current Smoking ◽

Exclusive Enteral Nutrition ◽

Male Sex ◽

Disease Location

Abstract Background Exclusive Enteral nutrition (EEN) is not routinely used as induction therapy for adults with active Crohn’s disease (CD)due to limited adherence and palatability. The aim of this study was to assess the efficacy, tolerability and safety of EEN in adult patients with CD. Methods Retrospective analysis of data from patients with active CD who underwent induction therapy with EEN at a single centre from January 2018 to July 2019. All patients who completed at least 4 weeks of polymeric EEN diet were included in the final analysis. Primary Endpoint (PE) was steroid-free clinical remission (CDAI ≤150) or response (100 point decrease in CDAI) at the end of therapy. Secondary endpoint (SE) was achievement of biochemical remission (CRP <5 mg/l or Calprotectin <150 μg/g) at 8–10 weeks. Results Sixty-three patients were initiated on EEN, 50 patients who completed at least 4 weeks of EEN were included in the final analysis. Mean age was 42.4 years, 25 (50%) were females. Mean CDAI score at baseline was 260. Forty per cent of patients were on concurrent biologics and 66.6% were on concurrent immunomodulators. At the completion of EEN, 72% (36/50) of patients achieved PE (29 remission, 7 response). SE was achieved in 65.7% (23/35) of patients. EEN duration ≥ 6 weeks was more likely to achieve PE (75% vs. 55.5%, OR 2.7, P 0.01) and SE (71% vs. 25%, OR 7.3, P 0.001).EEN duration < 6 weeks and current smoking were less likely to achieve PE and SE. Patients with concomitant steroid use at baseline had PE of 77.7% (vs. 68.8% with EEN alone; OR 0.9, P 0.5), and SE of 66.6% (vs. 60.9% with EEN alone, OR 0.77, P 0.74). Disease location, behaviour, sex, disease duration, concurrent biologic use or concurrent immunomodulator use did not affect the PE or SE. Six patients reported adverse effects (3 nausea,2 diarrhoea,1 constipation). Male sex, ileal location, B2/B3 phenotype were more likely to complete a 6 week EEN course. Conclusion Polymeric EEN is well-tolerated, safe and efficacious in inducing remission in adults with active CD. EEN duration of ≥ 6 weeks has better outcomes. EEN alone or in combination with steroids induces remission in adult patients with active CD. Further controlled trials using polymeric EEN are necessary.

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Exclusive enteral nutrition in the management of Crohn’s disease: a qualitative exploration of experiences, challenges and enablers in adult patients

Journal of Human Nutrition and Dietetics ◽

10.1111/jhn.12829 ◽

2020 ◽

Author(s):

R. N. Mutsekwa ◽

J. T. Edwards ◽

R. L. Angus

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Enteral Nutrition ◽

Adult Patients ◽

Exclusive Enteral Nutrition ◽

Qualitative Exploration

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Efficacy and tolerability of exclusive enteral nutrition in adult patients with complicated Crohn’s disease

Intestinal Research ◽

10.5217/ir.2019.09172 ◽

2020 ◽

Cited By ~ 1

Author(s):

Sanchit Sharma ◽

Arti Gupta ◽

Saurabh Kedia ◽

Samagra Agarwal ◽

Namrata Singh ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Enteral Nutrition ◽

Adult Patients ◽

Exclusive Enteral Nutrition

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Mucosal Healing and Bacterial Composition in Response to Enteral Nutrition Vs Steroid-based Induction Therapy—A Randomised Prospective Clinical Trial in Children With Crohn’s Disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjy207 ◽

2018 ◽

Vol 13 (7) ◽

pp. 846-855 ◽

Cited By ~ 14

Author(s):

Bénédicte Pigneur ◽

Patricia Lepage ◽

Stanislas Mondot ◽

Jacques Schmitz ◽

Olivier Goulet ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Enteral Nutrition ◽

Intestinal Microbiota ◽

Clinical Remission ◽

Molecular Mechanisms ◽

Mucosal Healing ◽

Bacterial Composition ◽

Exclusive Enteral Nutrition ◽

Index Of Severity

AbstractAimsExclusive enteral nutrition [EEN] is as efficacious as corticosteroids [CS] to induce remission in Crohn’s disease [CD], without their adverse effects. EEN seems to be more efficient than steroids to induce mucosal healing, but the underlying molecular mechanisms are only sparsely understood. We aimed in the present work to study the anti-inflammatory effects of EEN with Modulen IBD® vs CS in active paediatric CD, and to assess its modulatory effects on the intestinal microbiota as compared with steroids.Materials and MethodsNineteen patients with new-onset active CD (Harvey-Bradshaw index [HBI] >5), aged from 6 to 17 years, were included in this prospective randomised induction trial with CS [n = 6] or EEN [n = 13]. Patients were assessed at Weeks 0 and 8 using clinical parameters HBI, endoscopic findings (Crohn’s Disease Endoscopic Index of Severity [CDEIS] score) and analysis of faecal microbiota composition.ResultsAt 8 weeks, clinical remission [HBI <5] was achieved in 13/13 patients on EEN and 5/6 patients on steroids; the mucosal healing rate was significantly higher in the EEN [89%] compared with steroid group [17%]. There were no significant differences between groups regarding biological markers, but the intestinal microbiota profiles shifted upon EEN-induced remission to a higher proportion of Ruminococcus bacteria compared with steroid-induced remission [p = 0.049], and with higher proportions of bacteria belonging to Clostridium in EEN-treated patients.ConclusionsBoth steroid and EEN induced clinical remission. However, patients with EEN-induced remission showed a higher rate of mucosal healing and this was associated with a different gut microbiota compositional shift in these children.

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Review of exclusive enteral therapy in adult Crohn’s disease

BMJ Open Gastroenterology ◽

10.1136/bmjgast-2021-000745 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000745

Author(s):

Nikola Mitrev ◽

Hin Huang ◽

Barbara Hannah ◽

Viraj Chandana Kariyawasam

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Enteral Nutrition ◽

Opportunistic Infections ◽

Adult Patients ◽

Suboptimal Control ◽

Induction Treatment ◽

Major Drawback ◽

Exclusive Enteral Nutrition ◽

Mesh Terms

BackgroundExclusive enteral nutrition (EEN) is a potentially effective but underused therapy for Crohn’s disease (CD) in adults. It is first-line induction treatment for paediatric patients but remains a second-line or third-line therapy in adults.ObjectiveTo analyse the evidence for EEN in adult patients with CD, and summarise this in a narrative review.MethodsIn April/May 2020 and July 2021, a literature search was performed using the Medical Subject Headings (MeSH) terms: ‘Crohn’s disease’, ‘CD’, ‘inflammatory bowel disease’, ‘IBD’, ‘exclusive enteral nutrition’, ‘enteral nutrition’, ‘EEN’, in PubMed, Scopus, Cochrane. Additional studies were obtained from references of search result articles as well as general reading. Studies with adult patients with CD treated with EEN were selected. 79 articles of relevance were found. Where data in adults were lacking, data from paediatric studies as extrapolated with care.ResultsEEN in adult patients been shown to improve clinical, biomarker, endoscopic and radiologic measures of disease activity. EEN avoids the potential adverse effects of recurrent corticosteroids for induction such as metabolic derangements and opportunistic infections. EEN has also demonstrated benefits among adult patients with fistulising and stricturing CD. It may avoid surgery in such patients. Preoperative EEN has also been shown to reduce postoperative complications and recurrence. There appears to be benefits in combing EEN with antitumour necrosis factor agents, however, benefits of combination therapy with other biologics are less clear. A major drawback of EEN therapy in adults has been poor compliance. More palatable polymeric formulations improved patient education and dietitian support may overcome this. Evidence in adults is limited to small studies, often with suboptimal control arms and lack of blinding. Larger scale studies with improved study design are needed to confirm these beneficial effects.ConclusionDespite limitations in evidence EEN should be considered in treating adults with CD.

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DOP66 The effect of exclusive enteral nutrition on circulating inflammatory protein levels in paediatric patients with Crohn’s Disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab073.105 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S100-S101

Author(s):

M Pidoux ◽

M Logan ◽

S Milling ◽

U Z Ijaz ◽

R Hansen ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Enteral Nutrition ◽

Clinical Response ◽

Clinical Remission ◽

Innate Immune ◽

Plasma Samples ◽

Exclusive Enteral Nutrition ◽

Protein Levels ◽

Inflammatory Proteins

Abstract Background Exclusive enteral nutrition (EEN) is the recommended first line treatment for active paediatric Crohn’s disease (CD). The mechanism of action and immunological effects of EEN remain unclear. This study compared circulating inflammatory proteins of patients with CD and ulcerative colitis (UC) with non-inflammatory bowel disease (non-IBD) controls and explored the effect of EEN in children with active CD. Methods Patients with CD were treated with EEN for 8 weeks, with plasma samples collected prior to EEN start and upon EEN completion. Levels of 92 inflammatory proteins were quantified using Olink Inflammation panel. Paired faecal samples were collected to measure faecal calprotectin (FC) levels by ELISA. Patients in which FC decreased >50% during EEN were classed as FC responders; whereas patients who had a <50% decrease in FC were classed as FC non-responders. Results 84 patients were recruited (CD:54, UC:11, non-IBD:19). Paired plasma samples were collected from 18 patients with CD receiving EEN. Of these 18 patients, 72% achieved clinical remission by the end of EEN (wPCDAI <12.5 points). Prior to EEN start, 29 proteins were significantly different between patients with CD compared to non-IBD; and 25 proteins were significantly different between UC and non-IBD, Fig 1. EEN lead to the significant alteration of 23 proteins. This included 5 proteins, CCL23, CXCL10, IL6, IL24, and MMP-1 which were higher in patients with CD prior to EEN start compared to non-IBD, Fig 2. In patients who achieved clinical remission during EEN, 22 proteins significantly changed from their EEN start levels by the end of EEN, Fig 3. FC responders had a similar pattern of protein changes, in which 22 proteins changed significantly during EEN, Fig 4. 16/22 (72%) of the proteins that changed significantly in the FC responder group during EEN, also changed during EEN in patients who entered clinical remission including significant reductions in several innate immune proteins such as IL-6 and IL-18. Patients who did not achieve clinical remission did not have significant reductions in these proteins. Despite being higher in patients with CD prior to treatment compared to non-IBD, the level of 17 proteins, including IL17a and oncostatin M, did not change in FC responders during EEN. Conclusion EEN leads to alteration of multiple inflammatory proteins, in keeping with a reduction in innate immune pro-inflammatory activity and improvement in clinical response, although some inflammatory proteins remain elevated. Figure 1: Venn diagram of proteins significantly different Figure 2: Effect of EEN on protein levels Figure 3: Effect of EEN on protein levels, stratified based on clinical response during EEN Figure 4: Effect of EEN on protein levels, stratified based on FC response

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Exclusive enteral nutrition for induction of remission in anti-tumor necrosis factor refractory adult Crohn’s disease: the Indian experience

Intestinal Research ◽

10.5217/ir.2019.00094 ◽

2020 ◽

Vol 18 (2) ◽

pp. 184-191 ◽

Cited By ~ 1

Author(s):

Ajit Sood ◽

Arshdeep Singh ◽

Ritu Sudhakar ◽

Vandana Midha ◽

Ramit Mahajan ◽

...

Keyword(s):

Crohn’S Disease ◽

Tumor Necrosis Factor ◽

Crohn's Disease ◽

Enteral Nutrition ◽

Clinical Remission ◽

Tumor Necrosis ◽

Activity Index ◽

Exclusive Enteral Nutrition ◽

Number Of Patients ◽

Necrosis Factor

Background/Aims: Exclusive enteral nutrition (EEN) is recommended for induction of remission in pediatric Crohn’s disease (CD). However, it is not currently recommended for inducing remission in adults. This report describes the use of 12-week EEN for induction of remission in anti-tumor necrosis factor (anti-TNF) refractory adult CD.Methods: This is a retrospective analysis of adults with moderate to severe active (Crohn’s Disease Activity Index [CDAI] >220) anti-TNF refractory CD, who received EEN for 12 weeks between April 2018 and March 2019 at Dayanand Medical College and Hospital, Ludhiana, India. Primary outcomes included achievement of clinical remission and fistula healing at 12 weeks. Improvement in inflammatory markers and nutritional status were the secondary end points.Results: Out of 23 patients who received anti-TNF agents, 7 (30.4%) were refractory and were offered EEN as a salvage therapy. Six patients (66.7% females, mean age 25.6±6.5 years) consented. Four patients (66.6%) achieved clinical remission (CDAI <150). Mean CDAI of patients decreased significantly after 12 weeks of EEN (388.8±74.8 vs. 160.0±25.2, P<0.001). Perianal fistulas showed clinical response (drainage decreased by >50%), though none achieved remission. Entero-enteric fistulae showed complete healing. Mean body mass index improved from 15.6±3.1 to 18.9±1.9 kg/m2 at week 12 (P=0.003). Hemoglobin and serum albumin also improved from 8.2±1.1 g/dL and 2.8±0.3 g/dL at baseline to 12.6±0.6 g/dL and 3.6±0.5 g/dL post-EEN respectively (P<0.001 and P=0.006 respectively).Conclusions: EEN appears to be an effective and well tolerated therapy for induction of remission in anti-TNF refractory adult CD. More data from prospective trials with larger number of patients is required.

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