Role of Enteral Nutrition in Pediatric Crohn’s Disease

Joanna Yeh

Peds GI

Case Conference

May 2012

Objectives

• Understand the role of enteral therapy in treating Crohn’s disease

• Understand the differences in practice internationally

• Understand the pros and cons of enteral therapy

History

• First case reports in 1970s

• 1984: first controlled study to show elemental diet induced remission

• 2006: Europe and Japan independently published guidelines recommending enteral nutrition as first line induction therapy in children

• 2010: Similar conclusions by British society

• So why not in U.S.?

Pros

• Can induce remission

• Can maintain remission

• Reduced steroid dosage over long term (growth retardation, osteopenia)

• No major side effects

Cons

• Unpalatability

• Slower to get results

• Compliance concerns

• Costs/insurance

• Resource demands (nutritionist, nurse)

• QOL, psychosocial

International Variance

4%

36% 62%

Why does enteral therapy work?

• Unknown

• Hypotheses:

– Overall nutritional repletion

– Altered gut microflora

– Correction of intestinal permeability

– Decreased synthesis of inflammatory mediators via reduction in dietary fat

– Elimination of dietary antigen uptake

Steroid concerns

• Growth

• Bone mineral density

• Lack of mucosal healing

• Infections

• Psychosocial (depression, anxiety, loss of concentration, irritability, sleep disturbance)

“A stunted, cushingoid child without GI sx is not a success story”

Growth

• Positive effect of enteral therapy compared to steroids occurs within 10 week to 6 months

Mucosal healing

• New standard to aim for?

• Improved endoscopic and histologic scores with decreased mucosal inflammatory cytokines

• Documented in enteral therapy

Induction Therapy

• CHOP

– Semi elemental formula

– 90% of caloric needs from formula

– Nocturnal NG feeds (outpatient teaching program)

– Normal diet during day

– 7 days per week for 8-12 weeks

Induction therapy

• Cochrane 2007 meta analysis of 6 trials

• Steroids vs. enteral therapy

• Favored steroid therapy

• Adults and pediatrics but more adults

• 3 pediatric meta analysis

• Benefits of enteral therapy differ in children from adults?

Pediatric Meta Analysis

0

20

40

60

80

100

Healing of GI tract

Enteral nutrition Corticosteroids

0

20

40

60

80

100

Clinical improvement

Borrelli O, et al. Clin. Gastroenterol. Hepatol.; 2006

% %

n=19 n=18

P<0.05

Polymeric Diet Alone vs. Steroids for Active Pediatric CD

(Induction Therapy)

Duration of therapy

• Majority of centers use 6-8 weeks

• Inflammatory markers improve in as little as 1 week

• Time to remission 11 days to 2.5 weeks

• NASPGHAN group suggests a period of 3-4 weeks to see if therapy is effective

Remission Rates

• Induction – Range: up to 85% (53-80%)

– CHOP 75% at 12 weeks

– Steroid remission rates = 70-80%

• Maintenance – 32% at 1 year

– Old studies (1988, 1996) from Canada • At 12 month, 43% of enteral group relapsed vs. 79% in non

enteral group

– No recent studies

Maintenance Therapy • By itself or with medical therapy

• Options:

– Overnight NG feeds with normal daytime eating 5 days per week (CHOP)

– Short bursts of NG feeds every few months (“European”)

• i.e. 4 week cycles of exclusive enteral nutrition q3-4 months

– Oral supplements +/- medical therapy

Partial enteral therapy

• Lack of published data

• UK study of 50 children (Johnson, Gut, 2006)

• 100% of caloric needs seems better than 50% (15% vs. 42% remission)

• CHOP, unpublished data, allows 10% of energy intake as regular diet

Formula composition

• Comparisons between elemental, semi elemental, and polymeric (whole protein) show no significant differences

• ? Fat composition remains unclear, non significant trend favoring very low fat and low long chain triglyceride (larger trials needed)

Disease location

• Some evidence that enteral therapy works better in small bowel disease rather than in colonic disease but overall unclear

• Afzal (2005) – 11/12 with ileal disease achieved remission

– 32/39 with ileocolonic

– 7/14 with isolated colonic

• Buchanan (2009) – 10/13 with isolated small bowel

– 15/19 with isolated colonic

Reasons Preventing Widespread use of Enteral Therapy In U.S.

• Side effects: emesis, nausea, diarrhea, NG tube problems

• Compliance

• Psychosocial (food as an important social event)

• Lack of financial support

• Poor access to dietician/nursing support

• Lack of experience

• Lack of understanding of mechanisms of actions

• Lack of confidence in efficacy

Medical Therapies for Crohn’s Disease

• Induction: Steroids, anti TNF

• Maintenance: 6MP/AZA, MTX, anti TNF

• Mucosal healing: anti TNF > 6MP/AZA/MTX

• Improved growth: anti TNF > 6MP/AZA/MTX

Where does enteral therapy fit in?

Enteral Therapy in Crohn’s Disease

• Induction: Yes

• Maintenance: Yes

• Mucosal healing : Yes

• Improved growth : Yes

• Serious adverse events : No

Unanswered Questions

• Phenotype (SB vs. colonic)

• Induction protocol (100% vs. 90%)

• Maintenance protocol

• Induction Maintenance – Nutritional -> 6MP/AZA/MTX/anti TNF

– Steroid -> 6MP/AZA/MTX/anti TNF

Does induction with enteral therapy result in better long term outcomes? (height, bone density, mucosal healing, remission rate, etc.?)

Summary

• Enteral therapy is an effective induction therapy in newly diagnosed Crohn’s (grade A)

• Enteral therapy has an improved adverse effect profile over steroids (grade A)

• Enteral therapy improves mucosal healing, linear growth (grade A)

• Enteral therapy can be considered in the motivated, compliant patient

References

• Critch, et al, “Use of Enteral Nutrition for the Control of Intestinal Inflammation in Pediatric Crohn Disease,” JPGN, Feb 2012.

• Levine, et al, “Consensus and Controversy in the Management of Pediatric Crohn Disease: An International Survey,” JPGN, April 2003.

• Stewart, et al, “Physician Attitudes and Practices of Enteral Nutrition as Primary Treatment of Pediatric Crohn Disease in North America,” JPGN, Jan 2011.

• Heuschkel, et al, “Enteral Nutrition and Corticosteroids in the Treatment of Acute Crohn’s Disease in Children,” JPGN, July 2000.

• Zachos, et al, “Enteral Nutritional Therapy for Induction of Remission in Crohn’s Disease,” Cochrane Review, 2007.

• Borrelli, et al, “Polymeric Diet Alone Versus Corticosteroids in the Treatment of Active Pediatric Crohn’s Disease: A Randomized Controlled Open-Label Trial,” Clinical Gastroenterology and Hepatology, May 2006.