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

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

scholarly journals 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

2018 ◽  
Vol 13 (7) ◽  
pp. 846-855 ◽  
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.

Mucosal Biomarker of Innate Immune Activation Predicts Response to Vedolizumab in Crohn’s Disease

2019 ◽  
Author(s):  
Mark T Osterman ◽  
Ilyssa O Gordon ◽  
Elisabeth M Davis ◽  
Matthew Ciorba ◽  
Sarah C Glover ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Immune Activation ◽  
Clinical Remission ◽  
Response Rate ◽  
Intestinal Inflammation ◽  
Innate Immune ◽  
Clinical Response Rate ◽  
Innate Immune Activation

Abstract Objective Mucosal barrier dysfunction plays a crucial role in intestinal inflammation in Crohn’s disease (CD). Intestinal epithelial cell (IEC) death resulting from innate immune activation, termed pyroptosis, was recently found to be a cause of this barrier defect. The aim of this study was to determine the predictive value of pretreatment ileal biopsy pyroptosis as a biomarker for clinical response to vedolizumab in CD. Design Crohn’s disease patients ranging 18 to 80 years old from 5 IBD centers with pre-vedolizumab ileal biopsies during colonoscopy were enrolled. Biopsies were stained for activated caspases, and levels of ileal IEC pyroptosis levels were quantified. The primary outcome was clinical response 6 months after therapy, defined as a reduction of Harvey-Bradshaw Index (HBI) of ≥5 points from baseline. Secondary outcomes included clinical remission, defined as HBI <5, and endoscopic improvement, as measured by the Simple Endoscopic Score for Crohn’s Disease (SES-CD). Results One hundred CD patients (45 male, 55 female), median age 47 (19, 78) years, were included; clinical response rate was 60%, and clinical remission was 36%. The response rate in patients with ileal pyroptosis <14 positive cells per 1000 IECs was significantly higher than those above the threshold: 89% (25 of 28) vs 49% (35 of 72), odds ratio (OR) 8.8 (95% CI, 2.3–48.6; P < 0.001). Corresponding remission rates were 54% (15 of 28) vs 29% (21 of 72; OR 2.8 [1.03–7.59; P = 0.036]). For endoscopic improvement, ileal pyroptosis of 22 positive cells per 1000 IECs was the optimal threshold that determines the magnitude SES-CD change. Conclusions Ileal biopsy IEC pyroptosis was predictive of clinical response and endoscopic improvement to vedolizmab in CD patients.

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

2019 ◽  
Vol 12 ◽  
pp. 175628481988130
Author(s):  
Yihan Xu ◽  
Zhen Guo ◽  
Liangyu Huang ◽  
Jianfeng Gong ◽  
Yi Li ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Enteral Nutrition ◽  
Predictive Factors ◽  
Clinical Remission ◽  
Validation Cohort ◽  
Characteristic Curve ◽  
Adult Patients ◽  
Exclusive Enteral Nutrition ◽  
Colonic Lesion

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.

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

2020 ◽  
Vol 18 (2) ◽  
pp. 184-191 ◽  
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, <i>P</i><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/m<sup>2</sup> at week 12 (<i>P</i>=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 (<i>P</i><0.001 and <i>P</i>=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.

scholarly journals DOP01 Exclusive enteral nutrition for the treatment of adult Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S041-S041
Author(s):  
D Shukla ◽  
L Purcell ◽  
M Palmer ◽  
L Pillay
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Enteral Nutrition ◽  
Disease Activity ◽  
Cell Count ◽  
Clinical Response ◽  
White Cell Count ◽  
White Cell ◽  
Exclusive Enteral Nutrition ◽  
The Impact

Abstract Background Crohn’s disease (CD) is a debilitating autoimmune disease affecting &gt;40 000 Australians. Exclusive enteral nutrition (EEN) is an effective, risk-free therapy in children with CD, offering an ~80% success rate. Despite similar efficacy in adults, including the potential to decrease the need for high-risk steroids and surgery, adherence remains an unresolved obstacle for its use, with withdrawal rates of up to 40% (Wall 2013). Lack of dietetic expertise and support for adults on EEN were identified as primary barriers (Wall 2013). This prospective, single-centre, observational study aimed to assess the impact of a 6-week EEN model of care on disease symptoms, nutrition and inflammatory markers. We also assessed if &gt;80% of adults with CD could adhere to EEN. Methods Adults with active CD were treated with oral EEN for six weeks between March 2018 and September 2019 which uniquely included weekly specialist Dietetic support. EEN is the provision of 100% of a patient’s nutritional requirements via a nutritionally complete liquid formula. Paired assessment at baseline and EEN completion occurred for Crohn’s disease activity index (CDAI), calprotectin, C-reaction protein (CRP), platelets, albumin, white cell count, weight and calprotectin using paired t-tests. The primary outcome measure was disease activity using CDAI. Results Twenty-seven eligible CD patients were identified. Most patients (85%, n = 23/27) successfully adhered to EEN treatment (45 ± 13 years, 63% female, 52% had Calprotectin ≥100). The patients were further subdivided as per Montreal classification (L1:n = 12; L2:n = 3; L3:n = 12) and 93% were on medications such as steroids (n = 9/27), immunosuppressives (n = 19/27) and biologics (n = 16/27). After EEN, 74% (n = 20/27) achieved clinical remission (CDAI &lt;150) 19/27 patients (70%) achieved clinical response with &gt;70-point reduction in CDAI score and most (77%) patients achieved greatest improvement in CDAI score in the well-being section. A trend showed that 37% (p = 0.087) more patients with L2 and L3 CD achieved clinical response through CDAI than L1 CD patients. Calprotectin also showed a trend for improvement (-23(-65230-150) µg, p = 0.067, n = 20). No differences were observed in CRP, white cell count, or albumin (p = 0.262–0.433, n = 12–13); however, platelets showed a trend for improvement (-26(-156-46) µl, p = 0.071, n = 12) and weight reduced by −2.4(3.2) kg (p = 0.001). Few (30%, n = 8/27) patients changed medications during EEN treatment. No significant side effects were observed. Conclusion EEN may be achievable for most adults with additional professional support and has merit in assisting patients with clinical improvement of CD.

scholarly journals Predictors of Response to Exclusive Enteral Nutrition in Newly Diagnosed Crohn´s Disease in Children: PRESENCE Study from SEGHNP

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1012
Author(s):  
Melinda Moriczi ◽  
Gemma Pujol-Muncunill ◽  
Rafael Martín-Masot ◽  
Santiago Jiménez Treviño ◽  
Oscar Segarra Cantón ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Enteral Nutrition ◽  
Disease Activity ◽  
Clinical Remission ◽  
Activity Index ◽  
Newly Diagnosed ◽  
Faecal Calprotectin ◽  
Exclusive Enteral Nutrition ◽  
Paediatric Crohn’S Disease

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014–2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6–8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn’s Disease activity index [wPCDAI] < 12.5). Faecal calprotectin (FC) levels (μg/g) decreased significantly after EEN (830 [IQR 500–1800] to 256 [IQR 120–585] p < 0.0001). Patients with wPCDAI ≤ 57.5, FC < 500 μg/g, CRP >15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6–8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn’s disease regardless of the location of disease and disease activity.

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