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Summary Background The Crohn's disease exclusion diet (CDED) with partial enteral nutrition is effective for induction of remission in children with mild-to-moderate Crohn's disease. We aimed to assess the CDED in adults with Crohn's disease. Methods We did an open-label, pilot randomised trial at three medical centres in Israel. Eligible patients were biologic naive adults aged 18–55 years with mild-to-moderate Crohn's disease (defined by a Harvey–Bradshaw Index score of 5–14 points), a maximal disease duration of 5 years, with active disease on colonoscopy, or imaging with elevated inflammatory markers (C-reactive protein >5 mg/L or faecal calprotectin concentration >200 μ/g). Patients were randomly assigned (1:1) to CDED plus partial enteral nutrition or CDED alone for 24 weeks. Randomisation was via block randomisation (block sizes of six) using sealed, numbered, and opaque envelopes. Patients and investigators were aware of which group patients were assigned to due to the nature of the different interventions. The primary endpoint was clinical remission, defined as a Harvey–Bradshaw Index score of less than 5 at week 6. The primary endpoint was assessed in the intention-to-treat (ITT) population, which included all patients who used the dietary therapy for at least 48 h. We report results of the final analysis. This trial is registered with ClinicalTrials.gov , NCT02231814 . Findings Between Jan 12, 2017, and May 11, 2020, 91 patients were screened, of whom 44 were randomly assigned to the CDED plus partial enteral nutrition group (n=20) or CDED alone group (n=24). 19 patients in the CDED plus partial enteral nutrition group and 21 patients in the CDED alone group received the allocated intervention for at least 48 h and thus were included in the ITT analysis. At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618). Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group). 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group). No serious adverse events or treatment-related adverse events were reported in either group. Interpretation CDED with or without partial enteral nutrition was effective for induction and maintenance of remission in adults with mild-to-moderate biologic naive Crohn's disease and might lead to endoscopic remission. These data suggest that CDED could be used for mild-to-moderate active Crohn's disease and should be assessed in a powered randomised controlled trial. Funding Azrieli Foundation and Nestle Health Science.

OBJECTIVES Pediatric ulcerative colitis (UC) is characterized by low sustained remission rates and frequent extension of disease even if clinical remission is obtained with therapy. Moderate-to-severe endoscopic activity is a risk factor for relapse while prospective evidence regarding early mucosal healing or persistence of inflammation after remission in children is not available. Our aim was to evaluate if significant inflammation is common after clinical remission and could explain the high relapse rate in pediatric UC. METHODS Pediatric UC patients with clinical remission, defined as pediatric UC activity index (PUCAI) scores

Background Crohn’s disease exclusion diet (CDED) with partial enteral nutrition (PEN) is effective for induction of remission in children with mild-moderate Crohn’s disease (CD). Here we evaluated CDED in adults with CD. Methods This was an open-label prospective randomized controlled pilot trial in patients with mild-moderate CD defined as Harvey-Bradshaw Index (HBI) between 5–14, active disease on colonoscopy, or imaging with calprotectin>200 μ/gr. Group-I received CDED+PEN, and Group-II CDED-alone. A colonoscopy was performed at week-24. Endoscopic remission (ER) was defined as Simple Endoscopic Score for CD (SES-CD)≤3. The primary end-point was corticosteroid (CS) free remission defined as HBI Results Forty patients were included (median age 30 years [IQR;24–39], 19 patients- Group-I, 21 patients- Group-II). By intention-to-treat (ITT) analysis CS-free remission at week-6 was 62.5% of patients (25/40), comparable between Group-I 68.4%(13/19) vs.Group-II: 57.1%(12/21) (P=.46). Among remitters at week-6, sustained remission was present in 88%(22/25) week-12, and 80%(20/25) week-24. For patients with baseline elevated C-reactive protein (CRP) (n=30), median CRP decreased from 14.5 mg/L [IQR;7.7–37] to 8.4[IQR;5.4–18.5] at week6(P=.006), and to 8[IQR;5.4–20.6] week-24(P=.002). ER at week-24 was present in 14/28 patients (50%) and was 14/40(35%) by ITT. ER week-24 was similar between groups, 8/15(53.3%) vs. 6/13(46.1%) (P=.7). A comparison between baseline and week-24 SES-CD revealed a median of 5-points decrease (IQR; [-6.25]-[-1]), corresponding to 72.8% (IQR;20–100%) decline from baseline (P=.003). Conclusion CDED with or without PEN was effective for induction and maintenance of remission in adults with mild to moderate CD and may lead to endoscopic remission.

Background & Aims: Dietary therapies based on exclusion of usual dietary elements induce remission in children with Crohn's disease (CD), whereas re-exposure induces rebound inflammation. We investigated whether a short trial of dietary therapy, to identify patients with and without a rapid response or remission on the diet (DiRe), can be used to predict success or failure of long-term dietary therapy. Methods: We collected data from the multicenter randomized trial of the CD exclusion diet (CDED). We analyzed data from 73 children with mild to moderate CD (mean age, 14.2 ± 2.7 y) randomly assigned to groups given either exclusive enteral nutrition (EEN, n = 34) or the CDED with 50% (partial) enteral nutrition (n = 39). Patients were examined at baseline and at weeks 3 and 6 of the diet. Remission was defined as CD activity index scores below 10 and response was defined as a decrease in score of 12.5 points or clinical remission. Inflammation was assessed by measurement of C-reactive protein. Results: At week 3 of the diet, 82% of patients in the CDED group and 85% of patients in the EEN group had a DiRe. Median serum levels of C-reactive protein had decreased from 24 mg/L at baseline to 5.0 mg/L at week 3 (P

Background Pediatric ulcerative colitis (UC) is characterized by low sustained remission rates and frequent extension of disease even if clinical remission is obtained with therapy. Moderate to severe endoscopic activity is a risk factor for relapse while evidence regarding early mucosal healing or persistence of inflammation after remission in children is not available. Our aim was to evaluate if persistence of significant inflammation is common and could explain the high relapse rate in pediatric UC. Methods Pediatric UC patients with clinical remission, defined as pediatric UC activity index (PUCAI) scores < 10, were prospectively assessed for mucosal healing by endoscopy 3–5 months after remission was documented. Mayo score was assessed for each segment by a blinded adult gastroenterologist using central reading. Symptomatic patients prior to sigmoidoscopy were excluded Sustained remission was assessed retrospectively at 18 months follow-up. Results Forty-six children were enrolled, 28 children in continuous clinical remission at time of sigmoidoscopy were included in the final analysis. Mayo 0 was present in 12/28 (42.86%), Mayo 1 in 2/28 (7.1%) and Mayo 2–3 in 14/28 (50.0%) endoscopies. Among 23/28 patients with follow-up through 18 months, remission was sustained in 2/11 (18.18%) of patients with Mayo 2 and 3 versus 6/12 (50.0%) with Mayo score 0–1. Conclusion Over 50% of children assessed for mucosal healing 3–5 months after clinical remission is obtained have residual disease activity, primarily moderate to severe inflammation which was associated with lower sustained remission. Early sigmoidoscopy after clinical remission for assessment of mucosal disease should be considered in pediatric UC.

Background Pediatric ulcerative colitis (UC) is characterised by low sustained remission rates and frequent extension of disease even if clinical remission is obtained. Current therapy in pediatric UC is driven primarily by clinical response. Extension of disease and high relapse rates may be due to a failure to obtain mucosal healing with treatment despite clinical remission. Our aim was to evaluate this possibility by assessing endoscopic disease activity after remission was obtained. Methods Pediatric UC patients with clinical remission, defined as sustained PUCAI < 10 three months after remission was obtained, were prospectively assessed for mucosal healing by endoscopy. Mayo score was assessed for each segment by a blinded adult gastroenterologist using central reading. Results 41 children were enrolled after informed consent, 7 were excluded because of a PUCAI score 10–15 at the time of sigmoidoscopy. Thirty-four Sigmoidoscopies were performed 12–20 weeks after reporting clinical remission. Mucosal healing Mayo 0 was present in 15 endoscopies (44%), Mayo 1 was present in 2 endoscopies (6%) and moderate to severe endoscopic scores Mayo 2–3 was present in 17 endoscopies (50%). Conclusion About 50% of children assessed for mucosal healing 3–5 months after clinical remission is obtained have residual moderate to severe inflammation. Inadequate endoscopic improvement despite clinical remission may explain disease extension and the high relapse rate in children.

Background & Aims Exclusive enteral nutrition (EEN) is recommended for children with mild to moderate Crohn’s disease (CD), but implementation is challenging. We compared EEN with the CD exclusion diet (CDED), a whole-food diet coupled with partial enteral nutrition (PEN), designed to reduce exposure to dietary components that have adverse effects on the microbiome and intestinal barrier. Methods We performed a 12-week prospective trial of children with mild to moderate CD. The children were randomly assigned to a group that received CDED plus 50% of calories from formula (Modulen, Nestle) for 6 weeks (stage 1) followed by CDED with 25% PEN from weeks 7 to 12 (stage 2) (n = 40, group 1) or a group that received EEN for 6 weeks followed by a free diet with 25% PEN from weeks 7 to 12 (n = 38, group 2). Patients were evaluated at baseline and weeks 3, 6, and 12 and laboratory tests were performed; 16S ribosomal RNA gene (V4V5) sequencing was performed on stool samples. The primary endpoint was dietary tolerance. Secondary endpoints were intention to treat (ITT) remission at week 6 (pediatric CD activity index score below 10) and corticosteroid-free ITT sustained remission at week 12. Results Four patients withdrew from the study because of intolerance by 48 hours, 74 patients (mean age 14.2 ± 2.7 years) were included for remission analysis. The combination of CDED and PEN was tolerated in 39 children (97.5%), whereas EEN was tolerated by 28 children (73.6%) (P = .002; odds ratio for tolerance of CDED and PEN, 13.92; 95% confidence interval [CI] 1.68–115.14). At week 6, 30 (75%) of 40 children given CDED plus PEN were in corticosteroid-free remission vs 20 (59%) of 34 children given EEN (P = .38). At week 12, 28 (75.6%) of 37 children given CDED plus PEN were in corticosteroid-free remission compared with 14 (45.1%) of 31 children given EEN and then PEN (P = .01; odds ratio for remission in children given CDED and PEN, 3.77; CI 1.34–10.59). In children given CDED plus PEN, corticosteroid-free remission was associated with sustained reductions in inflammation (based on serum level of C-reactive protein and fecal level of calprotectin) and fecal Proteobacteria. Conclusion CDED plus PEN was better tolerated than EEN in children with mild to moderate CD. Both diets were effective in inducing remission by week 6. The combination CDED plus PEN induced sustained remission in a significantly higher proportion of patients than EEN, and produced changes in the fecal microbiome associated with remission. These data support use of CDED plus PEN to induce remission in children with CD. Clinicaltrials.gov no: NCT01728870 .