Risk stratification of pediatric IBD: What disease
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Transcript Risk stratification of pediatric IBD: What disease
RISK STRATIFICATION OF
PEDIATRIC IBD: WHAT DISEASE
PHENOTYPE DOES YOUR PATIENT
REALLY HAVE?
Ghassan Wahbeh MD
Associate Professor, Director IBD Program
Seattle Children’s Hospital
University of Washington
Content
Background
The natural history of pediatric IBD
Phenotypes and behavior
Complications
Can we predict pediatric IBD course?
Impact of mucosal healing
IBD: Age at presentation
0
10
20
Years
30 40
50
60
70
80
Percent of Cases
25
20
15
10
5
0
Loftus, Gastroenterology 2003; 124:abstract 278
Puberty
Social
Growth
Sexual
development
Development,
Bone
Independence
Density
Emotional
Growth,
Relationships
Wahbeh G et al. Inflamm Bowel Dis. 2008 Dec;14(12):1753
Challenges in Peds IBD
Early Diagnosis
Longer exposure to disease
Longer exposure to medication
Risk of adverse events
Medications
Testing
Presentation more severe than adult onset
Pediatric IBD: burden & opportunity
Achieving treatment
goals
Clinical remission
Restoring growth
&development
Restoring bone health
Mucosal healing
IBD does not end at
age 18-21 years
Response to therapy is
different in early IBD
Changing the natural
history
Can it be done?
Natural History of Pediatric IBD
Phenotypes, behavior & complications
Defining Disease
Phenotype
The observable properties of an organism
that are produced by the interaction of the
genotype and the environment
Phenotype evolution:
Extent
&
Behavior
Does the extent change and when?
Does the behavior change and when?
Crohn’s Disease: Initial Location
EUROKIDS
2004-2009
0-18 years
N = 582
L4:A+B: 4%
De Bie CL et al. Inflamm Bowel Dis. 2013 Feb;19(2):378-385
Crohn’s Disease: Location
EPIMAD
1998-2002
0-17 years
N = 281
Median f/u 84 months (52-124)
Vernier-Massouille et al. Gastroenterol 2008;135:1106–1113
Crohn’s Disease: Behavior & Surgery
34%
5 years
25
44%
Perianal 9-27%
first intestinal resection
EPIMAD
1998-2002
0-17 years
N = 404
Median f/u 84 months (52-124)
Vernier-Massouille et al. Gastroenterol 2008;135:1106–1113
Crohn’s disease Steroid therapy
3 months
1 year
84% complete or partial response
31% steroid dependent
8% surgery
N= 109
Markowitz J et a.l. Clin Gastroenterol Hepatol. 2006 Sep;4(9):1124-9.
Crohn’s disease at younger age
10% pediatric CD <5 years
IBDU more common
Perianal disease less common
Less aggressive behavior
IBD <2 years of age
IL10 & IL10 receptor dysfunction
Gupta N et al. Am J Gastroenterol. 2008 August; 103(8): 2092–2098
Glocker E et al. N Engl J Med 2009;361
Kotlarz D et al. Gastroenterology. 2012 Aug;143(2):347-55
IL10 & IL10 Receptor Mutations
Pre transplant
Day 108 post
Ulcerative colitis: Initial Location
Pancolitis
Left sided colitis
Extensive colitis
Proctitis
78%
18%
9%
5%
Atypical features
2004-2009
0-18 years
N=670
Rectal Sparing
5%
Backwash ileitis
10%
UGI lesions
4%
Levine A et al. Inflamm Bowel Dis 2012;000:000–000)
Ulcerative Colitis: Behavior
• 28% hospitalized within 3 years
• 36% with acute severe colitis steroid refractory
• 61% needed colectomy within 1 year pre biologics
Colectomy
1 year
5 years
8%
26%
Turner D et al. Am J Gastroenterol 2011; 106:574–588
Gower-Rousseau C et al. Am J Gastroenterol, 104(8), 2080-2088 (2009)
Hyams JS et al . J Pediatr, 129(1), 81-88 (1996)
UC Post surgical outcomes
Pouch complications
50% children will have ≥ 1 complication
Crohn’s of the pouch 6-13%
IBDU: progression and surgery outcomes
Ill defined in children
Wahbeh G et al. Expert Rev Gastroenterol Hepatol. 2013 Mar;7(3):215-23
Pediatric vs adult IBD
UC :
Pancolitis, steroid dependence more common
“atypical” features
Rectal Sparing
Fewer chronic architecture changes
CD:
More aggressive phenotypes
IBDU more common at younger age
Van Limbergen et al. Gastroenterology. 2008;135:1114-1122
Kugathasan S et al. J Pediatr. 2003;143:525-531
Hyams J et al. J Pediatr. 1988;112:893-898
Hyams JS, et al. Clin Gastroenterol Hepatol 2006;4:1118-1123
Vernier-Massouille G et al. Gastroenterology. 2008;135:1106-1113
Can we predict pediatric IBD
course?
Phenotype & behavior evolution
Risk of complications
Current risk assessment tools
Clinical picture at presentation
Labs & stool markers
Genetics
Serology
Microbiome?
Clinical predictors: IBD surgery
↑ Risk
Female gender
Poor growth
Abscess
Fistula
Stricture
↓ Risk
Younger age
Fever
Azathioprine
Infliximab
5-ASAs
Gupta N, et al. Gastroenterology 2006;130:1069-1077
Vernier-Massouille et al. Gastroenterol 2008;135:1106–1113
Deep ulcers: activity at 1 year
333 children with newly diagnosed CD
169: deep ulcers on initial colonoscopy
2.7 x active disease at 1 year
10 x less likely active disease if Anti TNF in 3 mo
Hyams et al. RISK CCFA study, DDW 2012
Labs & stool markers
Not useful to predict behavior
Predictive of disease relapse
CRP (Crohn’s)
Calprotectin
Genetics
Disease course
NOD 2 & IL23 R: limited predictive value
Steroid response
Infliximab response
De Iudicibus SJ Clin Gastroenterol. 2011 Jan;45(1):e1-7
Dubinsky et al. Inflamm Bowel Dis. 2010 Aug;16(8):1357-66.
Predictors of Phenotype & Complications
SB
pANCA
ASCA
Anti OMP-C
Anti CBir1
Anti I2
FS
IP
SB
surgery
UC-like
Mow et al. Gastroenterology 2004; 126(2):414-424
Papadakis et al. Inflamm Bowel Dis 2007:13(5):524-530
Dubinsky M. World J Gastroenterol. 2010 June 7; 16(21): 2604–2608
Antibody response sum & phenotype
Dubinsky et al. Clin Gastr Hep 2008;6:1105-1111
Serology & time to surgery
Can mucosal healing predict
phenotype change &
complications?
Impact of mucosal healing
↑ Steroid-free remission
↓ Hospitalization
↓ Surgery
Children without mucosal healing:
more likely to receive treatment change
Deep mucosal healing predicts sustained
clinical remission after stopping anti-TNF ab
Allez M et al. World J Gastroenterol 2010;16:2626e32
Froslie et al. Gastroenterology 2007:133(2):412-422
van Assche G, et al . Curr Drug Targets 2010;11:227e33
Thakkar K et al. Am J Gastroenterol 2009;104:722e7
Louis E et al Gastroenterology 2012;142:63e70.e65
Conclusions
• Pediatric IBD includes a spectrum of phenotype
severity
• The burden of pediatric IBD is substantial with
significant cumulative need for surgery
• Evolving role for disease behavior predictors
• Mucosal healing is a strong predictor of future
course
The end