Partial Enteral Nutrition Research Articles

Prospective cohort study on the effectiveness of the Crohn's disease exclusion diet + partial enteral nutrition in inducing and maintaining remission in adult patients with Crohn's disease

Prospective cohort study on the effectiveness of the Crohn's disease exclusion diet + partial enteral nutrition in inducing and maintaining remission in adult patients with Crohn's disease

Review article: Evidence-based dietary management of inflammatory bowel disease.

Dietary management of patients with inflammatory bowel disease (IBD) involves more than defining a therapeutic diet. The profusion of 'expert advice' is not necessarily built on evidence. To provide evidence-based guidance on all clinically relevant aspects of nutritional and dietary management of patients with IBD. A comprehensive review of the published literature was made. Four pillars of management should be considered in all patients. First, nutritional status should be optimised, since myopenia and visceral obesity are associated with poorer outcomes, which can be improved with attention to their correction. Accurate point-of-care measurement of body composition is advocated to identify problems, guide interventions and monitor outcomes. Second, exclusive enteral nutrition and the Crohn's Disease Exclusion Diet with partial enteral nutrition in reducing intestinal inflammation in patients with Crohn's disease have sufficient evidence to be advocated. Multiple other dietary approaches, while promising, have insufficient evidence to be recommended. Third, dietary approaches are important in symptomatic control in many non-inflammatory scenarios. Finally, guidance on following a healthy diet is fundamental to the general health of patients. Multiple approaches are advocated, but the optimal strategy is unclear. The precarious nutritional status of patients with IBD together with the risks of nutritional inadequacy and maladaptive eating behaviours associated with restrictive diets dictate involvement of expert dietitians in assessment and personalised delivery of dietary interventions. Four pillars of nutritional management require specific assessment and interventional strategies that should be chosen by evidence. Optimal delivery requires the skills of a specialised dietitian.

A real-life pediatric experience of Crohn's disease exclusion diet at disease onset and in refractory patients.

We aimed to appraise the real-life efficacy of Crohn's disease exclusion diet (CDED) coupled with partial enteral nutrition (PEN) in inducing clinical and biochemical remission at disease onset and in patients with loss of response to biologics and immunomodulators. We retrospectively gathered data of patients aged less than 18 years of age with a diagnosis of Crohn's disease (CD), who received CDED coupled with PEN at a tertiary level pediatric inflammatory bowel disease center. Sixty-six patients were identified. Forty (60.6%) started CDED plus PEN at disease onset and 26 (39.4%) received CDED with PEN as add-on therapy. Forty-six (69.7%) patients achieved clinical remission (weighted Pediatric Crohn's Disease Activity Index < 12.5) at the end of phase 1, 44 (66.7%) normalized c-reactive protein levels (<0.5 mg/dL) and 18 (27.2%) patients normalized calprotectin levels (<150 µg/g). Nine of 19 (47.3%) of patients with clinically severe disease (defined by Physician Global Assessment) achieved clinical remission at the end of phase I. Patients with extraintestinal manifestations had statistically lower clinical response rates to the dietary regimen (p = 0.018). Among patients who received CDED + PEN as add-on treatment, a previous successful course of Exclusive Enteral Nutrition was associated with statistically higher clinical remission rates at Week 8 (p = 0.026). Clinical response at Week 4 was an independent predictor of clinical remission and fecal calprotectin normalization at Week 8 (p = 0.002). CDED with PEN confirmed its efficacy in a real-life setting, proving to be effective also in refractory patients and those with severe disease. Early clinical response predicts clinical remission at the end of phase 1.

Preoperative Crohn's Disease Exclusion Diet and Exclusive Enteral Nutrition in Adults with Crohn's Disease: A Feasibility Randomised Controlled Trial.

Preoperative exclusive enteral nutrition (EEN) improves nutritional status, reduces intestinal inflammation, and likely improves surgical outcomes. Crohn's disease exclusion diet with partial enteral nutrition (CDED) also reduces intestinal inflammation but its safety preoperatively is unknown. This single-blinded, multicentre, randomised controlled trial of three preoperative nutritional therapies aimed to assess the feasibility of recruiting and retaining patients and collecting primary and secondary effectiveness outcomes. Adults undergoing elective Crohn's disease surgery with a body mass index (BMI) > 18.5 kg/m2 and without significant weight loss were eligible to participate. Patients were randomly assigned to six weeks of preoperative EEN, CDED, or standard care. Feasibility, nutritional, radiological, and surgical outcomes were recorded. Over 18 months, 48 patients were screened, 17 (35%) were randomised, and 13/17 (76%) patients were retained in the intervention phase. It was feasible to collect primary and secondary effectiveness data; at day 30, three patients had Clavien Dindo Grade 2 complications, and 10 had no complications. Nutritional therapy adherence of patients retained in the study was high. Recruitment and retention of patients who need elective Crohn's disease surgery for preoperative nutritional therapy is possible, although a shorter duration may improve EEN completion. The impact on surgical outcomes should be assessed in a larger study.

Revolution in diet therapy for inflammatory bowel disease.

Until recently, diet as a therapeutic tool to treat inflammatory bowel disease (IBD) has not been proven effective. Nearly a century in the making we are in the grips of a revolution in diet therapies for IBD, driven by emerging data revealing diet as a key environmental factor associated with IBD susceptibility, and observational studies suggesting that dietary intake may play a role in the disease course of established IBD. This review summarizes the current evidence for diets trialed as induction and maintenance therapy for IBD. For Crohn's disease, exclusive enteral nutrition and the Crohn's disease exclusion diet with partial enteral nutrition are supported by emerging high-quality evidence as induction therapy, but are short-term approaches that are not feasible for prolonged use. Data on diet as maintenance therapy for Crohn's disease are conflicting, with some studies supporting fortification, and others suppression, of certain food components. For ulcerative colitis, data are not as robust for diet as induction and maintenance therapy; however, consistent themes are emerging, suggesting benefits for diets that are plant-based, high in fiber and low in animal protein. Further studies for both Crohn's disease and ulcerative colitis are eagerly awaited, which will allow specific recommendations to be made. Until this time, recommendations default to population based healthy eating guidelines.

Effectiveness of a novel diet in attenuation of clinical activity of disease in patients with ulcerative colitis: a randomized, clinical trial

Dietary intake plays a pivotal role in ulcerative colitis (UC) initiation and prognosis. The aim of this study was to investigate the effect of a combined Mediterranean, low-FODMAP diet accompanied with partial enteral nutrition (PEN) on clinical and para-clinical characteristics of patients with UC. Fifty patients with active mild to moderate UC were received either a combined diet or a regular diet for 6 weeks. Before and after the intervention, disease activity index, quality of life and some inflammatory and oxidative stress factors were measured using valid and reliable questionnaires and blood sampling. Disease activity index was significantly decreased in the combined diet group in comparison to control diet group (p = 0.043), and baseline data (p < 0.001). Moreover, the quality of life score increased significantly in the combined diet group compared to the control group, and the baseline data (p < 0.001). Serum level of high sensitive C-reactive protein (hs-CRP) decreased significantly in the combined group (p < 0.01), while it increased in the control group non-significantly. Serum total anti-oxidant capacity (TAC) changes were not statistically significant in two groups. This study indicates that this combination diet has the potential to be used as a safe and highly effective approach in patients with significant intestinal symptoms. Further clinical trial studies with different duration of intervention are needed to confirm these results.Trial registration: The study was registered on IRCT.ir with registration number of IRCT20100524004010N38, on 25/04/2023.

Formula modifications to the Crohn's disease exclusion diet donot impacttherapy success in paediatric Crohn's disease.

The Crohn's disease exclusion diet (CDED) + partial enteral nutrition (PEN) is an emerging diet used to induce clinical remission in children with active Crohn's disease (CD). This study aims to determine the effectiveness of using the CDED+PEN to induce clinical remission in an Australian group of children with active CD using different PEN formulas and incorporating patient dietary requirements. We retrospectively collected data from children (both newly diagnosed and with existing CD while on therapy) with active CD (Paediatric Crohn's Disease Activity Index [PCDAI] ≥10)and biochemical evidence of active disease (elevated C-reactive protein [CRP], erythrocyte sedimentation rate [ESR] or faecal calprotectin [FC]) who completed at least phase 1 (6 weeks) of the CDED+PEN to induce clinical remission. Data werecollected at baseline, Week 6 and Week 12. The primary endpoint was clinical remission at Week 6 defined as PCDAI < 10. Twenty-four children were included in phase 1 analysis (mean age 13.8 ± 3.2 years). Clinical remission at Week 6 was achieved in 17/24 (70.8%) patients. Mean PCDAI, CRP, ESR and FC decreased significantly after 6 weeks (p < 0.05). Formula type (cow's milk based, rice based, soy based) did not affect treatment efficacy. A greater than 50% decrease in FC was achieved in 14/21 (66.7%) patients who completed phase 1 and 12/14 (85.7%) patients who completed phase 2 of the CDED+PEN. Formula modifications to the CDED+PEN do not impact the expected treatment efficacy in Australian children with active luminal CD.

A Short-Term Enteral Nutrition Protocol for Management of Adult Crohn's Disease-A Pilot Trial.

Crohn's disease (CD) is often treated with either exclusive or supplemental enteral nutrition (EN) in pediatrics, but adult practice guidelines primarily focus on medications. Here, we demonstrate the feasibility of a 4-week semi-elemental-formula-based oral nutrition delivery program for managing adult CD (n = 4). Patients consumed ~66% of calories from the formula, a finding that might provide an improved calorie target for future trials. We identified Flavinofractor as the only differentially abundant genus, distinguishing post-intervention samples from pre-intervention samples. Findings from this pilot trial demonstrate the feasibility of a partial enteral nutrition protocol in adult CD management and contribute to the growing body of literature on the potential role of EN therapy in adults with CD.

P681 Preliminary data from the Biologic and Partial Enteral Nutrition in Crohn’s Disease Study (BIOPIC)

Abstract Background Biologics such as adalimumab (ADA) are used to induce clinical remission (CR) in individuals with active Crohn’s disease (CD) but around 50% of patients actually achieve clinical remission. Exclusive enteral nutrition is also an effective induction treatment, but tolerability limits its use, especially in adults. This study aimed to assess the efficacy and tolerability of partial enteral nutrition (PEN) in combination with ADA compared to ADA monotherapy. Methods In this multi-centre (n=8) RCT (NCT04859088), adults with active CD (Crohn’s Disease Activity Index, CDAI ≥ 150) due to start ADA as their first-line biologic were randomised to either continue their habitual unrestricted diet (UD) or to replace half of it with PEN during their first 6 weeks of induction treatment Primary outcome clinical efficacy (i.e., clinical response, CDAI baseline decrease of ≥ 70 or CR, CDAI score &amp;lt;150) was assessed after 12 weeks of ADA initiation. Secondary outcomes included changes in inflammatory markers (faecal calprotectin, (FCAL), CRP) and quality of life (SIBDQ), at 3 (only FCAL), 6 and 12 weeks. To calculate adherence to PEN, used/unused tins were returned and compared to number provided. Analysis was performed using intention-to-treat analysis. Results 32 participants (13 UD, 19 PEN) have completed the study; 29 (13 UD, 16 PEN) of whom completed the full 12 weeks of the study. Adherence rate to PEN was high (~96%). Clinical efficacy (response &amp; remission) was UD: 92% vs PEN: 84%, p=0.490 at 6 weeks and UD: 85% vs PEN: 58%, p=0.11 at week 12. FCAL data was available for 22 participants (9 UD, 13 PEN). FCAL (g/g) significantly decreased after 12 weeks in patients receiving PEN (mean difference 189, p=0.009) but this effect did not quite reach statistical significance (p=0.052) in the UD group (Fig 1). Proportionally more patients from the PEN group had FCAL &amp;lt;100 mg/kg compared to the UD group (3, 6, 12 weeks, PEN: 62%, 69%, 69% vs UD: 33%, 33%, 56%) during the study course. CRP (mg/L) significantly decreased at week 6 and 12 in patients receiving PEN (week 6 &amp; week 12, p&amp;lt;0.0001) and in patients continuing their UD (week 6, p=0.001, week 12, p=0.007). SIBDQ score increased in both groups (PEN, p=0.023 vs UD, p=0.008). Conclusion Preliminary data from the BIOPIC study suggests equivalence in clinical efficacy between the two groups but better responses to blood and gut inflammatory markers when ADA is combined with PEN. High tolerability of PEN suggests it can be a viable option for adult patients with active luminal CD.

P919 Crohn’s Disease Exclusion Diet as add-on therapy in refractory pediatric patients

Abstract Background Despite the accumulating body of evidence of the efficacy and tolerability of Crohn’s disease exclusion diet (CDED) combined with partial enteral nutrition (PEN), there is still a paucity data regarding its use in combination with other medical treatments. We aimed at assessing its efficacy in re-inducing remission in pediatric CD patients experiencing disease relapse while on other maintenance therapies. Methods This was a single-center, retrospective, observational study conducted at an Italian national referral pediatric IBD center. Incident patients who received CDED coupled with PEN in the setting of the loss of response to other maintenance therapies from January 1st, 2020 to June 30th 2023 were included. Clinical remission at the end of each phase was defined by a weighted Pediatric Crohn’s Disease Activity Index (wPCDAI) below 12.5. Biochemical remission was defined by a c-reactive protein (CRP) lower than 0.5 mg/dL. A FC lower than 150 mg/kg was used as a surrogate of mucosal improvement (MI). Results 25 patients (52% males) met inclusion criteria and were included in the analysis. Median disease duration at CDED+PEN initiation was 31 months (Q1-Q3: 8.4-13.8). The most frequent disease location was ileocolonic (64%), 3 (12%) patients had isolated colonic involvement. 9 (36%) patients had stricturing/penetrating phenotype. 16 patients (68%) were being treated with an anti-TNF-alpha agent, whereas 5 (20%) patients were receiving ustekinumab (Table 1). wPCDAI, CRP and FC significantly decreased after the firs 8 weeks of treatment (22.5 vs 2.5, 1 vs 0.2, 640 vs 360, p&amp;lt;0.001, p=0.019 and p=0.007, respectively). At the end of phase I, 19/25 (76%) of the patients achieved clinical remission, 15 (60%) patients had CRP levels within normal range and 7 (28%) of them had normalized FC. 18/25 patients (72%) had received Exclusive Enteral Nutrition (EEN) for the induction of remission at diagnosis. Patients who achieved clinical remission with the EEN course (i.e.: a wPCDAI of &amp;lt; 12.5 after a complete course of EEN) were more likely to achieve clinical remission when receiving CDED + PEN (11/13 vs 1/5, p=0.022). Conclusion CDED coupled with PEN is a valid treatment strategy in the setting of secondary loss of response to maintenance treatments in children with CD. A previous successful course of EEN was associated with higher rates of clinical remission at the end of phase I, thereby possibly identifying a subset of “nutritional responder” patients.

P1207 Microbiome composition determines sustained remission after the Crohn’s Disease Exclusion Diet (CDED) with or without Partial Enteral Nutrition in adults with mild-moderate Crohn’s disease; Results from the CDED-AD Pilot Randomized Controlled Trial

Abstract Background The Crohn's Disease (CD) Exclusion Diet (CDED) is an established dietary therapy for children with active mild-to-moderate CD. A recent randomized controlled trial showed efficacy in mild-to-moderate CD in adults. We have previously demonstrated the impact of CDED on the microbiome of children. The aim of this work was to assess if we can determine sustained clinical remission (SCR) from the baseline microbiome composition and examine the effect of CDED on microbiome composition in adult CD. Methods This was an open-label, prospective, randomized, controlled pilot trial involving patients with mild-to-moderate CD and evidence of active inflammation. Patients were randomly assigned to receive CDED with partial Enteral Nutrition (PEN) or CDED alone, both for 24 weeks. The V4V5 region of the 16S rRNA gene was amplified and sequenced, and reads were processed using QIIME2 and the SILVA database. Relationships between the microbiome, SCR, and Fecal Calprotectin (FC) were analyzed using logistic regression, Poisson Principal Component Analysis, paired T-Tests and subsampling ranking forward selection. Results Clinical remission (CR) at weeks 6, 12 and 24 was achieved in 62.5%, 52.5%, and 50% of patients, respectively. Week 0, 6, 12 and 24 stool samples were available for 35,32,30 and 26 patients, respectively. In patients with SCR, defined as remission at both weeks 12 and 24, the baseline microbiome revealed lower alpha diversity compared to those without SCR (p=0.018), and differing Microbiome principal components (PC) scores (p &amp;lt; 0.01). PC1 and PC3, characterized mainly by Alistipes, Faecalibacterium and UCG-002 predicted SCR (P&amp;lt;0.01). PC2 predicted elevated FC&amp;gt;250 µg/g at week 12 (p=0.004). Baseline abundance of Haemophilus was associated with decreased SCR probability (p&amp;lt;0.01). At week 6 in the entire cohort, there was a significant decrease in Actinobacteriota (p=0.035) and a significant increase in Bacteroidota (p=0.003). Additionally, there was a significant increase in several genera, including beneficial Alistipes and Oscillibacter (p&amp;lt;0.02) in those who achieved CR after 6, 12, or 24 weeks. Higher Firmicutes at week 6 were associated with FC&amp;lt;250 at week 12 (p=0.031). An uncultured genus from the Oscillospiraceae family was significantly associated with a decrease in the probability of SCR (p&amp;lt;0.01) and was significantly increased at week 6 in patients who did not attain CR (p&amp;lt;0.05). Conclusion The baseline microbiome composition was associated with SCR and FC&amp;lt;250 at week 12 in adult patients treated with CDED (with or without PEN) over 24 weeks. This suggests that the microbiome could be useful tool to identify patients who would benefit from long-term dietary intervention.

P648 Dietary therapy using a short course of Exclusive Enteral Nutrition followed by the Crohn’s Disease Exclusion Diet in children with mild to severe Crohn’s Disease; maintenance update on the DIETOMICS trial

Abstract Background Exclusive enteral nutrition (EEN) is the first-line treatment for active Crohn’s disease (CD) in children. CD Exclusion Diet (CDED) combined with Partial Enteral Nutrition (PEN) has demonstrated better tolerance with a comparable effect in inducing remission among children with mild to moderate CD. This study evaluated the effectiveness of 2 weeks of EEN followed by CDED+PEN for maintaining remission for up to 24 weeks in children with mild-severe disease. Methods We conducted an international, multicenter, randomized controlled trial comparing 2 weeks of EEN using Modulen®, followed by 3 phases of the CDED+PEN (hereafter CDED), to 8 weeks of EEN followed by PEN with a free diet (hereafter EEN), all extended up to week 24 with a follow up till week 52. Children aged 8-18 with luminal CD duration less than 3 years, mild-severe disease [pediatric CD activity index (PCDAI),15-47.5], and active inflammation [elevated C-reactive protein (CRP),or fecal calprotectin (FC)] were included. Remission was defined as PCDAI≤10. Stable immunomodulator (IM) treatment was allowed, and naïve patients could initiate IM from week 4. Results We randomized 56 patients into two groups: Group CDED (n=30) and Group EEN (n=26); mean age 12.7±2.4, 37% female. Intention-to-treat analysis revealed remission in 18/30(60%) patients with CDED compared to 11/26(42%) with EEN at week 24,p=0.18 and 27% in CDED and 23% in EEN at week 52,p=0.75. Per protocol analysis showed 18/20(90%) remission in CDED compared to 11/14(78%) in EEN at week 8, p=0.35. Among patients who achieved remission at week 8, 18/23(78%) with CDED and 9/14(64%) with EEN maintained remission up to week 24, p=0.15. In CDED,15/20(75%) and 100% of EEN used IM, p=0.04. All CDED patients without IM remained in remission. Reduction of &amp;gt;50% in FC from baseline was obtained in 55% in the CDED and 28% in EEN, p=0.12. PCDAI improved from 31.2[20-35.6] to 5[0-12.5] in CDED and from 22.5[20-29.3] to 5[0-15.6] at week 24 in EEN, p&amp;lt;0.001 to all. CRP and FC significantly improved in both groups. Z score BMI improved from -1.3 [-2.1-(-0.1)] to -0.2 [-0.9-0.4], p=0.003 in CDED and from 0.08[-1.1-0.4] to 0.2[-1.7-0.7] at week 24 in EEN,p=0.098. Remission at week 2 (p=0.006) and overall high compliance (p=0.009) were identified as predictors of response at week 24. Conclusion While 2 weeks of EEN followed by CDED+PEN was not superior to EEN at 14 weeks (as previously reported), extending CDED+PEN for 24 weeks successfully maintained remission for up to 52 weeks in children with mild-to-severe CD. Moreover, a subset of patients maintained sustained clinical remission following CDED monotherapy. The long-term implementation of dietary therapy using CDED+PEN resulted in a significant improvement in nutritional status.

P721 Dutch Crohn’s disease patients’ (pediatric and adult) perspectives of CDED diet and Modulife program

Abstract Background The Crohn’s Disease Exclusion Diet (CDED) with partial enteral nutrition can induce remission in patients with mild-to-moderate Crohn’s disease. As adherence is the key of (possibly) success of a medical therapy and CDED might be a complicated diet to perform, we aimed to investigate patients’ experience with CDED and the available tools (Modulife programme) to improve patientcare. Methods All mild-to-moderate active Crohn’s disease (CD) (adult and pediatric) patients treated with CDED as nutritional therapy as part of their medical treatment at Amsterdam UMC between 2019-2022 were approached for this retrospective qualitative study. A structured telephone interview was conducted by a dedicated dietician/doctor with the patients and/or parent/guardian in case of children. Questions about CDED-experience and Modulife program were either measured with the NET Promotor Score (NPS -100 - +100), as yes/no answer options or with 5-point likert scales (1=strongly agree/always to 5=strongly disagree/never). Lastly, patients were asked to evaluate the effectiveness of CDED on complaints and experience on a scale from 0-10. Results 44 patients (33 pediatric/11 adults; 26 women) participated in the interviews. The majority (61%) of the pediatric patients started CDED at diagnosis. The remaining 39% started 1-11 years (median 3[IQR 2-5]) after diagnosis at an age of 7-17 years (median 15[IQR 12-16]). 91% of the adult patients started CDED 3-37 years (median 11[IQR 4-28]) after diagnosis and only 1 immediately after diagnosis at an median age of 48 [IQR 33-60] (range: 19-69). The majority of the pediatric participants would recommend CDED to others (77%) and consider to start the diet again (55%). All of the adults would recommend CDED to others and consider to start CDED again. The NPS scores on CDED experiences are shown in figure 1. The median score for the effect of the diet on complaints was 8[IQR 5-9] (range 0-10) and 7[IQR 6-7](range 2-8.5) for experience. The majority of the patients (75%) used the Modulife program always or often during therapy and did (strongly) agree that the Modulife program was helpful. A NPS of 31 was given for recommending the app to others. The recipes-feature was the most used and most esteemed part of the app and was assessed with a good NPS of 27 for recommendation to others. Conclusion The majority of the pediatric and all of the adult participants would recommend CDED to others and would reconsider starting the diet again. CDED is better assessed by adults (positive NPS) then children and/or their parents (negative NPS). Most of the patients, assess the Modulife programme very positively and the majority would rate this as helpful in performing the diet.

P518 Dietary and non-dietary predictors of treatment response to adalimumab in anti-TNFα-naïve adults with Crohn’s disease

Abstract Background Biologics, such as anti-TNFα agents, are commonly used in the management of Crohn’s disease (CD). A significant proportion of patients do not respond to treatment, necessitating the exploration of pre-treatment predictors of treatment response. Methods Anti-TNFα-naïve adults with active CD (Crohn’s Disease Activity Index; CDAI≥150) participating in an RCT (NCT04859088) were randomised to receive adalimumab monotherapy or adalimumab combination therapy with 50% partial enteral nutrition (PEN). Treatment response (CDAI&amp;lt;150) was assessed after 6 weeks, baseline diet was assessed with EPIC-Norfolk FFQ, alternative Mediterranean diet scores (aMED), and principal component analysis (PCA) with orthogonal (varimax) rotation was used to identify data-derived dietary patterns. Baseline predictors evaluated included PEN use, steroid use, immunomodulator use, age, disease duration, CDAI, C-Reactive protein (CRP), albumin, haemoglobin, Scottish Index of Multiple Deprivation (SIMD) score, adherence to dietary patterns identified, aMED score, smoking status, alcohol consumption, physical activity level, body mass index (BMI), fat mass (kg/m2), fat-free mass (kg/m2), and handgrip strength. Differential analysis between responders and non-responders was carried out with general linear model or chi-square test when appropriate. Random forest model with recursive feature elimination (RF-RFE) was used to identify the most predictive factors of treatment response. Results Of 42 participants recruited to the study, 62% (26) responded to treatment. PCA revealed four dietary patterns (Figure 1A). Responders to adalimumab were younger (mean (SD): 36.0 (17.1) vs 50.8 (10.0), P=0.004), had lower baseline CDAI (mean (SD): 228 (62) vs 286 (78), P=0.018), higher CRP (14.5 (19.2) vs 4.6 (5.8) mg/L, P=0.036), were less likely to smoke (31% (5 of 16) vs 8% (2 of 26), and less likely to adhere to a dietary pattern characterised by high consumption of animal products (PC2) (P=0.030). Adherence to PC2 also correlated positively with age (r=0.327, P=0.035). The RF-RFE algorithm highlighted young age, low baseline CDAI and low PC2 adherence as key factors (Sensitivity: 77%, Specificity: 63%, PPV: 77%, NPV: 63%, OOB: 29%, P=0.012) (Figure 1B). Interestingly, exclusion of dietary factors improved diagnostic performance of the model (Sensitivity: 77%, Specificity: 75%, PPV: 83%, NPV: 67%, OOB: 24%, P=0.003) (Figure 1C), indicating potential interactions by other factors like age. Conclusion Young age, non-smoking, low baseline CDAI and elevated CRP predict adalimumab response in anti-TNFα-naïve adults. While dietary factors may also play a role, their impact seems confounded by other non-dietary factors. Further research is warranted in this area.

P354 Tryptophan metabolites as predictive biomarkers for dietary therapy outcomes in paediatric Crohn's disease

Abstract Background Crohn's disease (CD) exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) are effective in inducing remission in mild-to-moderate paediatric CD. While tolerance is higher with CDED+PEN than with EEN, a subset of patients still does not achieve remission. Diet-induced remission at week 6 was associated with changes in tryptophan (Trp) metabolism.1 Our aim was to investigate whether baseline Trp metabolites could predict dietary therapy outcomes in paediatric CD. Methods In total, 26 mild-to-moderate treatment-naive paediatric CD patients from a prior randomized controlled trial 2, were classified as having remission 6 (R, n =19 (CDED+PEN=10 and EEN=9)) and No-Remission (NR, n=7 (CDED+PEN=3 and EEN=4)) following 6 weeks of CDED+PEN or EEN therapy, based on the Paediatric Crohn’s Disease Activity Index (PDCAI) score (≤10 remission, &amp;gt;10 no remission). We performed targeted quantitative analysis of 21 tryptophan metabolites in baseline faecal samples from both groups, utilizing liquid chromatography coupled with quadrupole mass spectrometry. Receiving Operator Characteristic Curve (ROC) and Random Forest Analysis were used to assess the predictive power of Trp metabolites for dietary outcomes. Results Baseline clinical characteristics were comparable between R and NR. Baseline fecal kynurenine was significantly higher in NR compared to R for CDED+PEN (p=0.02) (Fig 1A) and EEN (p=0.04) (Fig 2A). ROC analysis highlighted the robust predictive power of kynurenine for CDED+PEN (area under the curve (AUC)=0.97) (Fig 1B) and EEN (AUC=0.88) (Fig 2B) induced remission. Random Forest analysis corroborated these observations. Ratios of Trp metabolites were compared to investigate different downstream Trp pathways. The ratio serotonin/kynurenine was the strongest predictor of CDED+PEN-induced remission (AUC=1) (Fig 1C). The ratio 5-OH-Tryptophan/kynurenine (AUC=0.88) (Fig 2C) predicted EEN-induced remission. When data from CDED+PEN and EEN were combined, kynurenine (AUC=0.91) and the ratios of quinolinic acid/kynurenine (AUC=0.93) and kynurenine/indole-3-acetic acid (AUC=0.88) demonstrated strong predictive performance for dietary therapy in general (Fig 3A,B and C). Conclusion Baseline faecal kynurenine has potential as a prognostic biomarker for dietary therapies. Trp metabolite ratios, notably serotonin/kynurenine for CDED+PEN and 5-OH-tryptophan/kynurenine for EEN, showed promising predictive capabilities. If confirmed in validation studies, baseline faecal Trp markers may be able to provide much needed guidance to personalize dietary intervention within the management of paediatric CD.

Prospective study of an adalimumab combined with partial enteral nutrition in the induction period of Crohn’s disease

BackgroundAdalimumab monotherapy can suppress gut inflammation and induce remission in active Crohn’s disease but has some limitations. Exclusive enteral nutrition (EEN) is recommended for patients with mild to moderate Crohn’s disease (CD), but implementation is challenging.AimTo evaluate the effectiveness of adalimumab combined with partial enteral nutrition (PEN) in the induction therapy for Crohn’s disease.MethodsA prospective cohort study was designed and a total of 56 patients with active CD who met the criteria for enteral nutrition (EN) treatment in our hospital were selected. The baseline data of all patients were collected including age, sex and other general information. The changes in fecal calprotectin, C-reactive protein (CRP), albumin(Alb), hemoglobin (Hb), platelets (Plt), erythrocyte sedimentation rate (ESR), Crohn’s disease activity index score (CDAI), simple endoscopic score (SES-CD) and body mass index (BMI) were compared between the adalimumab combined with enteral nutrition (ADA+EN) group (N = 37) the adalimumab group (ADA) (N = 19) at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated. Then the ADA+EN group was divided into an adalimumab combined with exclusive enteral nutrition subgroup (ADA+EEN) and an adalimumab combined with partial nutrition subgroup (ADA+PEN) according to enteral nutrition intake. The changes in fecal calprotectin, CRP, Alb, Hb, Plt, ESR and CDAI, SES-CD and BMI were compared between the ADA+EEN group and the ADA+PEN group at week 0 (W0) and treatment outcomes at week 12(W12). The differences between the two groups before and after treatment were evaluated. To evaluate the effectiveness of the two treatments on patients’ quality of life, nutritional recovery and body composition, patients in the ADA+EN group were needed to complete the Inflammatory Bowel Disease Questionnaire (IBDQ), EQ-5D-5L, the EuroQol visual analogue scale (EQ-VAS) and body composition analysis.A total of 28 patients completed all questionnaires and body composition analyses at week 0 and week 12, including 10 patients in the ADA+EEN group and 18 patients in the ADA+PEN group, respectively. The differences of in IBDQ, EQ-5D-5L and body composition analysis were compared between the two groups at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated.ResultsThese investigated indexes such as calprotectin, Hb, Plt, ESR, Alb, BMI, CRP, CDAI and SES-CD scores were significantly different before and after treatment in the ADA+EN group (p < 0.01). However, fecal calprotectin, Hb, SES-CD scores and Alb in the ADA group were not statistically significantly different from W0 to W12 (p > 0.05). The fecal calprotectin and CDAI scores in the ADA+EN group were significantly lower than those in the ADA group after treatment. The differences in all factors before and after treatment between the ADA+PEN group and the ADA+EEN group were statistically significant (p < 0.05). However, there was no significant difference between the two groups at week 12 (p > 0.05).ConclusionAdalimumab combined with EN are more effective than ADA monotherapy in terms of endoscopy and clinical remission. By comparing the investigated indicators such as calprotectin, Hb, Plt, ESR ,CRP and SES-CD scores, it was proven that adalimumab combined with partial enteral nutrition or exclusive enteral nutrition has the same remission effect in induced Crohn’s disease. The combination of biological agents and partial nutrition can improve medical order compliance, psychological burden and quality of life. Therefore, adalimumab combined with partial nutrition can be used as the first-line treatment for CD induced remission.

Effectiveness of Partial Enteral Nutrition as Add-On to Biologics in Patients With Refractory and Difficult-to-Treat Crohn's Disease: A Pilot Study.

Partial enteral nutrition (PEN) is a well-established treatment for children with Crohn's disease (CD). However, its efficacy in adults with CD remains uncertain. We aimed to assess the effectiveness of PEN as an add-on to escalated biological therapy in adults with CD who have lost response to biologics. We conducted a retrospective observational study including patients who had lost response to biologics and received PEN in combination with escalated treatment, compared to those treated only with escalated therapy. The primary endpoint was steroid-free clinical remission (CR) at 24 weeks. Secondary endpoints included transmural healing (TH) and response (TR) rates along with selected clinical outcomes. Forty-two patients were screened; 12 (28.6%) were excluded for complicated disease and 30 (71.4%) were included in the final analysis. Fourteen (46.7%) patients completed PEN treatment at 8 weeks, while 16 patients (53.3%) discontinued treatment due to intolerance and continued with escalation of biologic (BT group). At 24 weeks, 9 patients (64.3%) in the PEN group achieved CR, compared to 4 patients (25%) in the BT group (P = .03). The TR rate was 64.9% in the PEN group and 25% in the BT group (P = .03). Patients receiving PEN exhibited an increase in albumin levels compared to those in the BT group (Δ = 0.5; P = .02). A higher rate of therapy changes (68.7%) was observed in the BT group compared to 14.2% in the PEN group (P = .004). Prior failure to 2 lines of biological therapy was associated with adherence to PEN (OR = 1.583; CI = 1.06-2.36; P = .01). In patients who had lost response to biologics, PEN in combination with escalated biologics was associated with CR and TR and improved nutritional status. Hence, the addition of PEN should be considered for patients with difficult-to-treat CD.

Perceptions Toward Established and Novel Dietary Therapies for Crohn's Disease Management Among Adult Patients: Results From a Questionnaire Survey.

Exclusive enteral nutrition (EEN) and partial enteral nutrition (PEN) remain the only established dietary therapies in Crohn's disease (CD) management. We conducted a questionnaire survey to evaluate the perceptions of adults with CD toward established and emerging food-based dietary therapies. A 26-question anonymous survey was mailed to 300 adults receiving biologic treatment. Two researchers independently conducted a thematic analysis of open-ended responses. Machine learning with the Random Forest-Recursive Feature Elimination algorithm identified predictors of willingness to try dietary therapies. One hundred and sixty patients (53% female) completed and returned the survey. Forty-two percent were following some form of exclusion diet, with low-spice and low-fiber diets being the most popular. Although only a quarter of patients believed that EEN/PEN could help with their CD, more than half believed that diet could help, with another 13% already using diet for CD management. While half of the patients were willing to try EEN, the majority were willing to try PEN instead (51% vs. 79%; P < .001). Forty-two percent of patients preferred food-based dietary plans prepared at home over EEN/PEN options. The most important predictors for willingness to try dietary therapies were age (25-65 years), recent symptoms, previous exposure to EEN/PEN, and current exclusion diet use. The top concerns about PEN were taste/palatability, satiety/hunger, and taste fatigue. Most adults preferred to follow a food-based dietary therapy over EEN/PEN. The majority would try PEN though which allows for more flexibility to incorporate in habitual diet and may be easier to comply with than the EEN.

Treatment of Crohn’s disease with complex fistula disease using an exclusion diet

Exclusive Enteral Nutrition (EEN) is considered the standard of care for the treatment of children with Crohns Disease (CD) but it is rarely used in adults. The main reason for this might be severe dietary restrictions, resulting in a reduced quality of life and a lack of compliance with the diet. The development of less restrictive dietary strategies has improved therapy adherence and thus also the success of the therapy in recent years. The therapy of fistulas in CD is generally considered difficult and nutritional therapy for fistulas has not been systematically investigated. We present the case of a patient with fistulizing CD. Immunosuppressive therapy with a biological was complicated by urothelial carcinoma, and an alternative treatment had to be found. In our patient, Crohns Disease Exclusion Diet (CDED) and Partial Enteral Nutrition (PEN) resulted in normal stool consistency and frequency, and one and a half years after the start of the exclusion diet, the patient remains in clinical remission.

Practical application of the Crohn's disease exclusion diet as therapy in an adult Australian population.

There is demand from patients and clinicians to use the Crohn's disease exclusion diet (CDED) with or without partial enteral nutrition (PEN). However, the therapeutic efficacy and nutritional adequacy of this therapy are rudimentary in an adult population. This review examines the evidence for the CDED in adults with active luminal Crohn's disease and aims to provide practical guidance on the use of the CDED in Australian adults. A working group of nine inflammatory bowel disease (IBD) dietitians of DECCAN (Dietitians Crohn's and Colitis Australian Network) and an IBD gastroenterologist was established. A literature review was undertaken to examine (1) clinical indications, (2) monitoring, (3) dietary adequacy, (4) guidance for remission phase, and (5) diet reintroduction after therapy. Each diet phase was compared with Australian reference ranges for food groups and micronutrients. CDED with PEN is nutritionally adequate for adults containing sufficient energy and protein and meeting >80% of the recommended daily intake of key micronutrients. An optimal care pathway for the clinical use of the CDED in an adult population was developed with accompanying consensus statements, clinician toolkit, and patient education brochure. Recommendations for weaning from the CDED to the Australian dietary guidelines were developed. The CDED+PEN provides an alternate partial food-based therapy for remission induction of active luminal Crohn's disease in an adult population. The CDED+PEN should be prioritized over CDED alone and prescribed by a specialist IBD dietitian. DECCAN cautions against using the maintenance diet beyond 12weeks until further evidence becomes available.