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Ghassan Wahbeh MD Associate Professor, Director IBD Program Seattle Children’s Hospital University of Washington.

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Presentation on theme: "Ghassan Wahbeh MD Associate Professor, Director IBD Program Seattle Children’s Hospital University of Washington."— Presentation transcript:

1 Ghassan Wahbeh MD Associate Professor, Director IBD Program Seattle Children’s Hospital University of Washington

2 Content  Background  The natural history of pediatric IBD  Phenotypes and behavior  Complications  Can we predict pediatric IBD course?  Impact of mucosal healing

3 IBD: Age at presentation 010 20304050 6070 80 Percent of Cases 25 20 15 10 5 0 Loftus, Gastroenterology 2003; 124:abstract 278 Years

4 Puberty Growth Sexual development Social Development, Independence Emotional Growth, Relationships Bone Density

5 Wahbeh G et al. Inflamm Bowel Dis. 2008 Dec;14(12):1753

6 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

7 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?

8 Phenotypes, behavior & complications Natural History of Pediatric IBD

9 Defining Disease  Phenotype The observable properties of an organism that are produced by the interaction of the genotype and the environment  Phenotype evolution: Does the extent change and when? Does the behavior change and when? Extent & Behavior

10 Crohn’s Disease: Initial Location De Bie CL et al. Inflamm Bowel Dis. 2013 Feb;19(2):378-385 EUROKIDS 2004-2009 0-18 years N = 582 L4:A+B: 4%

11 Crohn’s Disease: Location Vernier-Massouille et al. Gastroenterol 2008;135:1106–1113 EPIMAD 1998-2002 0-17 years N = 281 Median f/u 84 months (52-124)

12 Crohn’s Disease: Behavior & Surgery Vernier-Massouille et al. Gastroenterol 2008;135:1106–1113 first intestinal resection 34% 5 years Perianal 9-27% 25 44% EPIMAD 1998-2002 0-17 years N = 404 Median f/u 84 months (52-124)

13 Crohn’s disease Steroid therapy N= 109 Markowitz J et a.l. Clin Gastroenterol Hepatol. 2006 Sep;4(9):1124-9.. 3 months 1 year 84% complete or partial response 31% steroid dependent 8% surgery

14 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

15 IL10 & IL10 Receptor Mutations Pre transplant Day 108 post

16 Ulcerative colitis: Initial Location Pancolitis78% Left sided colitis18% Extensive colitis9% Proctitis5% Levine A et al. Inflamm Bowel Dis 2012;000:000–000) 2004-2009 0-18 years N=670 Atypical features Rectal Sparing5% Backwash ileitis10% UGI lesions4%

17 28% hospitalized within 3 years 36% with acute severe colitis steroid refractory 61% needed colectomy within 1 year pre biologics Ulcerative Colitis: Behavior 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) Colectomy 1 year8% 5 years26%

18 UC Post surgical outcomes  Pouch complications  50% children will have ≥ 1 complication  Crohn’s of the pouch 6-13% Wahbeh G et al. Expert Rev Gastroenterol Hepatol. 2013 Mar;7(3):215-23 Ill defined in children IBDU: progression and surgery outcomes

19 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

20 Phenotype & behavior evolution Risk of complications Can we predict pediatric IBD course?

21 Current risk assessment tools  Clinical picture at presentation  Labs & stool markers  Genetics  Serology  Microbiome?

22 Clinical predictors: IBD surgery Gupta N, et al. Gastroenterology 2006;130:1069-1077 ↓ Risk Younger age Fever Azathioprine Infliximab 5-ASAs ↑ Risk Female gender Poor growth Abscess Fistula Stricture Vernier-Massouille et al. Gastroenterol 2008;135:1106–1113

23 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

24 Labs & stool markers  Not useful to predict behavior  Predictive of disease relapse  CRP (Crohn’s)  Calprotectin

25 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.

26 Predictors of Phenotype & Complications SBFSIPSB surgery UC-like pANCA  ASCA  Anti OMP-C  Anti CBir1  Anti I2  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

27 Dubinsky et al. Clin Gastr Hep 2008;6:1105-1111 Antibody response sum & phenotype

28 Serology & time to surgery

29 Can mucosal healing predict phenotype change & complications?

30 Impact of mucosal healing  ↑ Steroid-free remission  ↓ H ospitalization  ↓ S urgery  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

31 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

32 The end

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