The New Kid on the Block The Crohns

The New Kid on the Block: The Crohn’s Disease Exclusion Diet for Induction of Remission Rotem Sigall Boneh, RD Clinical and research dietitian Wolfson Medical Center, Holon, Israel October 18, 2019 Chicago, IL

Disclosures § Speaker for Nestlé Health Science and Takeda § Consulting for Nestlé Health Science

Why use the CDED? Includes whole food, easier to perform and maintain compared to EEN, with better tolerance Offers effective treatment for short and long terminduction and maintenance of remission Includes fiber and substrates required to produce SCFA Is designed to be nutritionally balanced

The Crohn’s Disease Exclusion Diet (CDED) § Previously demonstrated in case series ü CDED+PEN induced remission, decreased inflammation in children and adults and was associated with mucosal healing ü CDED+PEN induced remission and decreased inflammation in children and adults who LOR to anti-TNFα Sigall Boneh et al. Inflamm Bowel Dis 2014; 00: 1 -8 Sigall Boneh et al. J Crohns Colitis. 2017 Oct 1; 11(10): 1205 -1212

Crohn’s Disease Exclusion Diet + PEN vs. Exclusive Enteral Nutrition Gastroenterology 2019 CDED+PEN EEN 50% EN Exclusive EN Western Diet Habitual Diet Triggering Crohn’s Disease Increased Proteobacteria Dysbiosis, Intestinal permeability, Inflammation, Active Disease Western Diet CDED Remove Animal Fat Wheat Dairy Red Meat Emulsifiers Maltodextrin Carrageenan Add Fruits Vegetables Crohn’s Disease Exclusion Diet+PEN vs. EEN Primary endpoint: CDED+PEN is better tolerated than EEN Secondary endpoints: Both CDED+PEN and EEN are effective to achieve remission at week 6 CDED+PEN is superior to sustain remission and reduce inflammation at week 12 CDED+PEN: associated with reduction in Proteobacteria and Intestinal Permeability Levine A et al. Gastroenterology 2019; 157: 440 -450

CDED Trial - RCT comparing CDED+PEN to EEN followed by PEN 78 patients mild to moderate CD , mean age 14. 2± 2. 7 years Levine A et al. Gastroenterology 2019; 157: 440 -450

Primary and secondary endpoints Similar Response and Remission Week 6 p=0. 002 p=0. 52 100 p=0. 36 p=0. 51 p=0. 14 97. 5 80 82. 5 Percent 73. 7 85. 3 85 76. 5 60 80 73. 5 75 58. 8 40 20 0 Tolerance Good compliance Response CDED EEN Remission PCDAI≤ 10 Remission PCDAI<10

Change in median PCDAI and CRP baseline & week 6 P<0. 001 27. 5 30 25 P<0. 001 25 24 23. 6 20 15 10 5 5 2. 5 5 4. 1 0 PCDAI CDED PCDAI EEN CRP CDED Baseline PCDAI CRP EEN week 6 CRP; mg/L 8

What happens by week 12? Sustained remission week 12 IMM Week 6 -12 CDED 37. 5% vs. EEN 45%; P=0. 6 P=0. 04 P=0. 01, OR 5. 5 (1. 48 -20. 42) 100 85. 5 80 75. 9 75. 6 56 60 45. 1 47. 6 40 20 0 Remission PCDAI<10 Normal CRP remission Sustained remission PCDAI<10 CDED+PEN EEN

Median Calprotectin changes over 12 weeks 3500 3126 3000 P=0. 001 P=0. 026 2647 2500 2000 P=0. 002 P=0. 01 1744 1589 1500 1021 1000 732 500 0 CDED+PEN Calpro Wk 0 E E N Calpro wl 6 Calpro wk 12

Microbiome & intestinal permeability Normal Intestinal Permeability Lactulose Mannitol week 0 and week 3 Baseline 46% Week 3 69% Improved Baseline 56% Week 3 56% No Change

Allowed foods Mandatory foods 50% Partial Enteral Nutrition Foods with reduced exposure Excluded Foods Crohn’s Disease Exclusion Diet Developed by Prof. Arie Levine

The C D E D Sustainable Multi-seasonal Progressive Exposure No regional limitation Balanced, allows growth Palatable Reduction in exposure to dietary componen ts is the ded d a s Food ection rr for co biosis of dys prove im and to tional nutri s statu main mech anism of action Increased: § Fruits and Vegetables and Resistant Starch § High quality of lean protein sources Contains: § Complex carbohydrate § Healthy oils Reduced: § Animal and saturated Fat § Taurine § Wheat § Heme/iron § Emulsifiers § Maltodextrins § Carrageenans § Sulphites § Dairy products KEEP IT BALANCED

CDED – Mandatory and allowed foods

CDED – Disallowed food

CDED- Program for life Phase 1 6 weeks Phase 2 6 weeks Maintenance Lifestyle 9 months Self restriction • Induction of • remission Restricted • phase 50% PEN • More foods • includes 25% PEN • CDED principles • Free meals • 25% PEN • The first 12 weeks are “All or None” It will only work if patients adhere to it properly

Recipe booklet Mobile App Support the patients Trained dietitian Handout

Patient support platform- by HCP only Track food intake, diet adherence and well being Watch videos with helpful tips for each phase of CDED diet Access a robust database of CDED-friendly recipes and meal plans Message nutrition experts about the CDED diet, anywhere, anytime HCP- Health Care Professional

CDED history and near future First CDED RCT; 2019 IBD, 2014 JCC, 2017 CDEDADULTS; 2021 DIETOMICS-CD; 2021

Conclusions § CDED+PEN is an effective treatment for induction of clinical and biochemical remission after 6 weeks as shown in RCT § Re-exposure to free diet after EEN increased inflammation and reduced sustained remission § CDED+PEN allows patients an easier treatment approach with the same efficacy as EEN § CDED is a nutritional balanced, sustainable, palatable, multi-seasonal dietary program with an established support system; including recipes, mobile app and HCP training sessions § The CDED+PEN program should be used as instructed, especially during the first 12 weeks § More studies are warranted

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