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Therapeutic Diets for IBD: What is the Evidence?
Lindsey Albenberg, DOChildren’s Hospital of PhiladelphiaCenter for Pediatric Inflammatory Bowel DiseaseAssistant Professor of PediatricsDivision of Gastroenterology, Hepatology, and Nutrition
Presented March 10, 2020
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Financial Support for this presentation was provided by Nestlé Health Science.The views expressed herein are those of the presenter and do not necessarilyrepresent Nestlé’s views. The material herein is accurate as of the date it waspresented, and is for educational purposes only and is not intended as asubstitute for medical advice.
Reproduction or distribution of these materials is prohibited.
Beaugerie L, Kisrchgener J. Clin Gastroenterol Hepatol 2019
Safety concerns…
19 Beaugerie L, Kisrchgener J. Clin Gastroenterol Hepatol 2019
Safety concerns…
• Patients with IBD exposed to thiopurines exhibit an increased risk of cancers. • Young patients, particularly males, are at risk of postmononucleosis lymphomas and hepatosplenic T‐cell lymphomas.
• Patients with IBD exposed to thiopurines exhibit an increased risk of nonmelanocytic skin cancers
• Patients exposed to anti‐TNF agents are at increased risk of melanoma.
• Whether patients treated with anti‐TNF agents alone exhibit an excess risk of lymphoma remains controversial.
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• Because it makes sense !
• Medications have limited efficacy
• Medications are not a cure !
• Safety concerns
• Children with IBD have a lifetime of treatment ahead of them
• Enteral nutrition (EN) is a term used to describe the use of a liquid nutrition formula administered orally or through nasogastric tube for the treatment of CD
– Replacing all or the majority of daily calories with formula and excluding or limiting food
• Dates back to the 1970’s when the use of TPN and elemental formula diets were reported as potential treatments for CD
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Meta‐analysis: EEN vs Steroids
Induction of remission: equivalent; OR 1.26 (0.77, 2.05) favoring EEN
Mucosal Healing: EEN is superior: OR 4.5 (1.46, 12.23)
Swamimanth et al., Aliment Pharmacol Ther 2017;46:546‐56. 27
Defined Formula Diets for CD
PCDAI CRP CDEISHistol ‐Ileum
Histol ‐Colon
Polymeric diet ‐ Pre 38.1 10.4 12.9 10.4 10.7
Polymeric diet ‐ Post 6.53 2 5.9 3.8 4.6
Corticosteroids ‐ Pre 35.5 11.9 12.7 11 11.1
Corticosteroids ‐ Post 7.5 2.2 9.8 9.6 8.8
0
5
10
15
20
25
30
35
40
45
Group M
ean
*
*
* * * *
*
10 Week open label RCT in newly diagnosed children with Crohn’sPolymeric diet (n=19) vs. Steroids (n=18)
* P<0.05 for Pre vs Post
Borrelli O. Clin Gastroenterol Hepatol 2006;4:744‐53 28
Elemental vs. Nonelemental
Response to Dietary Therapy
0
20
40
60
80
100
Elemental Nonelemental
Adapted from Zachos M. Cochrane Review 2007
No difference
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EN for Induction of Remission in CD: Duration of Therapy
• 6‐8 weeks most common in the literature (range 4‐12 weeks)• Clinical response seen at 4 weeks (Rubio et al. 2011, PCDAI and Guo at al. 2013., CDAI)
• PLEASE Study: Prospective cohort study of children with Crohn disease from Philadelphia (used Peptamen), Toronto (used Modulen) and Halifax (used Osmolite); (n=90)
– Enteral therapy with defined formula diet (38) vs. anti‐TNFα therapy (52)
– PCDAI measured at baseline and 8 weeks
– Stool for calprotectin (FCP) and microbiome• measured at baseline, 1 week, 4 weeks, and 8 weeks
Lewis JD, et al. Cell Host & Microbe 2015; 18: 489 30
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27 28
29 30
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EN for Induction of Remission in CD: Duration of Therapy: PLEASE study
• The microbiota composition among the EEN‐treated group changed within 1 week of therapy
• Significant reduction in FCP by week 4
Lewis JD, et al. Cell Host & Microbe 2015; 18: 489 31
0
10
20
30
40
50
60
70
FCP<50 FCP<250
0
14
5
45
30
62
Percentage of Patients
Calprotectin Concentration at Week 8 (mcg/g)
Partial EnteralNutrition (n=16)
Exclusive EnteralNutrition (n=22)
Anti‐TNF (n=52)
**
*p< 0.05 EEN vs anti‐TNF** p<0.05 PEN vs EEN and PEN vs. anti‐TNF
Lee, et al. Inflamm Bowel Dis 2015;21:1786‐92
For Induction of Remission, How Exclusive is Exclusive?
Similar amounts of formula intake for the Partial EN and Exclusive EN groups
• Literature very heterogenous, difficult to assess systematically
• Systematic review of 12 studies (3 RCTs, only 1 evaluated to be low risk of bias) of EN for inactive CD (children and adults) concluded EN more effective than regular diet and as effective as some medications in maintaining remission (El‐Matary et al. Journal of Parenteral and Enteral Nutrition. 2017.)
– Could not perform metaanalysis
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Where should we place EEN?
• Most common placement of EEN observed in the literature: alternative to corticosteroid as a bridge to thiopurine
• Scarce data evaluating combination of EEN with other therapies (1 study with anti‐TNF)
• Bridge to PEN for maintenance?
• Bridge to exclusion diets?
• Bridge to anti‐TNF (delayed insurance approval, allow immunization catch‐up in unimmunized, patients with intra‐abdominal abscess)
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Exclusive Enteral Nutrition: Pros and Cons
+ At least as effective as steroids
+ Associated mucosal healing
+ Works quickly
+ Improves nutritional status
+ Improves bone health
+ No side effects
‐ Demands resources, education, & dedication
‐ Limited long‐term benefit
‐ Exit strategy?
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CD‐TREAT: Emulating EEN with food
• Hypothesis: Ordinary food diet based on composition of Modulen formula can achieve similar efficacy as EEN for treatment of Crohn’s
• Diet: – Avoid gluten, lactose– Match macronutrients, vitamins, minerals, and fiber– Food delivered by catering company
• Results:– 28 Healthy adults: similar effects on microbiome and metabolome
– 5 children with Crohn’s: 4 improved, 1 discontinued because of symptom exacerbation
Svolos V. Gastroenterology. 2018.40
The Specific Carbohydrate Diet (SCD)• Restricted foods on the SCD:
– All grains
– Refined sugars
– Cow’s milk products (fully fermented yogurt ok)
– “Processed foods”
• Popular following in the community for variety of GI illnesses
– Anecdotal evidence plentiful
• Concerns: Elimination of whole food groups from the diet, inadequate calories, emotional well‐being
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Author Study design n Summary
Two ongoing multicenter trials: 1) n‐of‐1 study of SCD and modified SCD (120 participants)2) SCD vs. Mediterranean diet (194 participants)
9 Nutrient intake comparable to 2012 NHANES reference group for protein, vitamins, minerals
Obih C, Nutrition (2016)
Retrospectivecase series
26 Improved clinical and laboratory parameters for Crohn’s disease and UC
Suskind DL, Dig Dis Sci (2016)
Patient survey 417 Majority of respondents perceive clinical benefit to SCD
Burgis JC, World J Gastro (2016)
Retrospectivecase series
11 Improved labs, growth parameters
Kakodkar S, J AcadNut Diet (2015)
Retrospectivecase series
50 SCD is effective for some adults with IBD; High quality of life reported
Suskind DL, J Ped Gastro Nut (2014)
Retrospectivecase series
7 Improvement in clinical + lab parameters (Hct, CRP)
Cohen SA, , J Ped Gastro Nut (2014)
Prospective case series
16 Clinical and mucosal improvements seen
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39 40
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Crohn’s Disease Exclusion Diet is Equally Effective but Better Tolerated than Exclusive Enteral Nutrition for Induction of Remission in Mild to Moderate Active Paediatric
Crohn’s Disease: A Prospective Randomized Controlled Trial
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CDED Trial ‐ RCT comparing CDED+PEN to EEN followed by PEN
78 patients mild to moderate CD , mean age 14.2±2.7 years
Week 6: Comparison EEN vs CDED + PEN (50% calories from formula)
Levine A. Gastro. 2019. 46
Week 6 PCDAI and CRP
Levine A, Gastro. 2019. 47
Median FCP weeks 6 and 12
Levine A, Gastro. 2019.
Rebound at week 12 in EEN group with transition to 25% formula, 75% free diet
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CDED RCT Conclusions
• Large (relatively)! And randomized, controlled!
• Not powered to be an efficacy trial but as good (? better) than EEN for induction of remission
• Mild disease cohort with short disease duration (<36 mos)
• No mucosal healing endpoint, but significant reduction in FCP
• Long term outcomes unknown
– Will patients achieve mucosal healing with diet alone by 6 months?
– Is the diet sustainable long term?
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Conclusion• Exclusive enteral nutrition (EEN) is effective therapy for Crohn’s
• Restriction diets involving regular food have shown promise
• There are limitations to the clinical data for dietary therapy in IBD. This should not be a deterrent. – Shared decision making and following objective outcomes closely are critical– Consider dietary therapy ”a drug”
• I expect the same compliance with therapy and with monitoring and willingness to move on if therapy not working
• Further studies on dietary therapy needed, particularly those that address mechanism
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Questions
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