Prof Andrew Day Paediatric Gastroenterologist Christchurch, NZ
PIBD Case reports What is IBD all about Approaching and diagnosing IBD Management principles The future
1
2/09/15
JF 13 year old boy Presents with 18 m 12 m 6m
abdo pain, weight loss (7 kg), lethargy no increase in height loose motions (mucousy)
JF No longer swimming Missing school ++ Mother Crohn’s colitis from 18 y Uncle & cousin Coeliac disease
2
2/09/15
JF ESR 55 Platelets 558 CRP 43
Albumin 27 Hb 97
? IBD - scopes & small bowel imaging
BM Follow Through Wall thickening Irregularity TI stricture
3
2/09/15
JF UGIE: erythematous stomach: granulomatous gastritis Colonoscopy: aphthoid ulceration ileo-caecal region, active and chronic inflammatory changes
JF Long history pain, diarrhoea, weight loss
Ileocolonic CD with upper gut involvement
4
2/09/15
JF Commenced on Exclusive Enteral Nutrition 9 drinks daily 8 weeks Commenced Azathioprine week 2 Full dose week 4
JF Week 2 CRP 17, Weight gain 1.2 kg Back to school, energy improved Week 8 CRP 4, ESR 13, Alb 36 Weight gain 5.3 kg Ongoing followup…
5
2/09/15
CH – 12 year old boy Diarrhoea 6 weeks 3-4 day/ 1-2 nocte Bloody, loose, mucous occ vomit intermittent pain weight loss (1-2 kg) anorexia, lethargy
6
2/09/15
CH Stools (x4) WBC+++ No Clostridium, no pathogens Calprotectin
>500
ESR 2, CRP0.05 p=0.0003
p=0.002
Serum CrossLaps (ng/ml)
4 3 2 1 0 Control
CD Baseline CD Post EEN
41
2/09/15
Biologic therapies As more of the complex puzzle of immune system in gut is explained, more places to focus new therapies: Development of biologic therapies
42
2/09/15
Infliximab First biological agent to be used in Crohn’s Given to > 1 million people worldwide in last decade Indications:
Severe, unresponsive disease Fistulizing disease
Dosing:
5 mg/kg at 0, 2, and 6 weeks
Structure of Infliximab
Native (mouse) Antibody
Chimeric
Infliximab - a chimeric antibody (25% mouse derived, 75% human protein)
Humanized (Primatized™)
Human Protein Mouse Protein
43
2/09/15
Infliximab: Mechanism of Action Binds & neutralizes soluble & membrane bound TNFα - inhibits further activity = TNFα
Natalizumab Α4β1 Integrin inhibitor (CNS and gut) IV injection CD (and MS) Associated PML
Vedolizumab Gut selective integrin antagonist α4β7 integrin
45
2/09/15
Certolizumab
Pegylated anti-TNF inhibitor (Cimzia) Monthly s.c. injections CD
Others on the horizon… Mongersen – oral, enhances TGF-β Golimumab – human IgG1 monoclonal TNFα Tofacitinib – JAK inhibitor Ustekinumab – IL-12/IL-23 (p40) inhibitor Faecal Transplant – cautious anticipation Mesenchymal stem cells
46
2/09/15
Worm therapy The Hygiene Hypothesis Less exposure to infections including parasites Infections impt in development of immune system in gut ? Different responses without early priming
“Worm therapy” Pig whip-worm (Tricuris suis) Infects pigs: no human infection Trials with eggs (TSO): transiently live in gut Change type of response in the gut Prevent release of inflammation-causing proteins Promote release of protective proteins
47
2/09/15
“Worm therapy” in adults UC: 13 of 30 (43.4 %) got better with TSO over 12 weeks (controlled with placebo). CD: 21 of 29 (72.4%) under control at 12 and 24 weeks Treatment safe in short term No long-term data Subsequent data less clear
