1. Pediatric IBD Research
STAKEHOLDER REVIEWER TRAINING PROGRAM
Pediatric IBD Research
Michael D. Kappelman, M.D.,M.P.H.
Pediatric Gastroenterology, and
Center for GI Biology and Disease
University of North Carolina at Chapel Hill

2. Children With IBD: Not Small Adults!

3. Nor large mice!

4. IBD in Children
Everything Dr. Long taught last night applies to children
Similarities between children and adults with IBD
GI symptoms
Extra-intestinal manifestations
Diagnostic testing
Treatment goals
Medical treatments
Surgical Treatments

5. IBD in Children: Unique Issues
Presentation is more severe in children
Crohn’s disease: ~20% risk of
surgery/complicated disease
UC: Higher incidence
of pancolitis (>80%)
Delay in growth and puberty
Psychological and emotional impact on children
Risks (and benefits) of medications
Van Limbergen Gastroenterology 2008

6. Epidemiology of Pediatric IBD
Peak age of onset is between yrs.
Prevalence = 1.2 million Americans
~50-75K IBD patients are < 18 years (5%)
~25% of patients with IBD will have onset of symptoms under the age of 18 yrs.
Annual incidence = 7/100,000 children
Kugathasan, et al J. Pediatr

7. Is it 25% or 5%? Incidence: # new cases/time period
Prevalence: total # cases at a given time
Prevalence = incidence * average duration
IBD: No cure (yet), near normal life expectancy
Long duration
Even if 25% of IBD is diagnosed during childhood, those individuals spend most of their lives as adults

8. Disease Costs Annual disease-attributable costs for IBD: $6.3 billion
Kappelman, et al Gastroenterology
Annual disease-attributable costs for IBD: $6.3 billion
*Costs greater in children vs. adults

9. Presentation of IBD in Children
Crohn’s disease (n=386)
Abdominal pain - 86%
Diarrhea - 78%
Blood in stool - 49%
Weight loss – 80%
Fever – 38%
Perianal lesions – 44%
Ulcerative colitis (n=195)
Abdominal pain 69%
Diarrhea – 93%
Blood in stool – 95%
Weight loss – 55%
Fever – 15%
Griffiths and Buller in Walker: Pediatric Gastrointestinal Disease (2000)

10. The Effect Of IBD On Growth
Growth often affected in children with IBD
More common in CD than in UC
Seen both before and after disease is diagnosed
Adult height may be compromised
CD: 32-88%
UC: 9-34%
Growth marker for disease
activity

11. The Effect Of IBD On Growth
“Growth window”
Pre - pubertal
Crucial to minimize time between symptom onset, diagnosis, and treatment

12. Causes of poor growth Intestinal inflammation Inadequate oral intake
Abdominal pain, anorexia, nausea
Diarrhea and nutrient losses
Steroids
Disease location

13. Pubertal Delay in IBD
Similar factors affecting growth affect onset of puberty
Poor nutrition
Pro-inflammatory cytokines
Delayed age of peak height velocity (middle of puberty) in Crohn’s disease, but not UC
~1/4 children with Crohn’s
Delay usually 6-12 months

14. Bone Density in IBD
Maximum accumulation of calcium in bone occurs in mid-teen years
Decreased bone mineral density common in children and adolescents with IBD
Poor calcium absorption/inadequate calcium intake and vitamin D deficiency (~36%)
Decreased physical activity
Inflammation
Steroid use increases short and long term risk
Shifts balance between bone formation to bone breakdown and fat cell production

15. Promoting Growth and Bone Health
Control inflammation
Induce remission
Maintain remission
Ensure adequate caloric intake
For some, high calorie supplements may be needed
Ensure adequate calcium and vitamin D
Avoid long-term or repetitive steroid use

16. Psychological Challenges
Specific issues facing patients
Being a teen is hard enough!
Defining what it means to have a chronic illness
Physical symptoms associated with IBD affect patients’ self-image
Coping with procedures, frequent clinic visits, and hospitalizations
Adhering to complicated medical/dietary regimens
Greater risk of low self-esteem, poor social functioning, and depression
When a child is faced with a chronic illness he or she may struggle with these issues: review each
Being aware of and addressing these challenges early on promotes the best types of adaptation.

17. Treatment Challenges Limited data
Treatment data taken from adult studies
Trials do not consider child-specific outcomes
Unanswered questions
Do medications work as well (or better) in kids?
Are there differences in safety?
Infections
Malignancy
*Impact of lifetime therapy duration
Practical considerations, not “one size fits all”
Swallowing medications
Ease of following a regimen

18. Absolute versus Relative
Relative risk (or benefit): Drug A doubles the chances of an outcome (remission, infection)
Absolute risk (or benefit): The actual probability that the event will occur.
For patients, its absolute risk that matters:
Doubling the chances of a rare event = a rare event
Important concept in peds, as the baseline risk of malignancy and serious infections is much lower

19. Risk of Developing Non-Hodgkin’s Lymphoma
Patient with Crohn’s disease
Estimated annual risk =
2 per 10,000 treated patients
Courtesy of Corey Siegel

20. Risk of Developing Non-Hodgkin’s Lymphoma
Patient with Crohn’s disease receiving 6MP or Azathioprine
Estimated annual risk =
4 per 10,000 treated patients
Courtesy of Corey Siegel

21. Towards Personalized Medicine
IBD is not two diseases, but dozens
Selecting the right treatment for the right patient at the right time is the ultimate goal
Balancing risk and benefits
Using clinical factors (symptoms, inflammation, growth/skeleton, psychological well-being)
Incorporating state of the art science (genetics, immunology, microbiome)

22. First visit to the clinic… Patient-specific treatment plan
IBD 2015 and beyond…
First visit to the clinic…
IBD Panel
Serology
Genetics
Proteomics
IBD Subtype
Disease Prognosis
Patient-specific treatment plan