Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview...
Transcript of Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview...
![Page 1: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/1.jpg)
Inflammatory Bowel DiseaseA selected overview
Dr Richard Gearry
Department Of Gastroenterology, Christchurch Hospital
Dr Richard GearrySenior Lecturer, Department of Medicine, UOC
Consultant Gastroenterologist, Christchurch Hospital
Medical Director, Digestive Health Services Ltd
Medical Advisor, Christchurch Crohn’s and Colitis Support Group
![Page 2: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/2.jpg)
Who am I?
• Gastroenterologist with a passion for IBD• Born and bred in Christchurch• House Surgeon Nelson / Christchurch• House Surgeon Nelson / Christchurch• Gastroenterology Registrar, Christchurch• PhD “Aspects of IBD in Canterbury”• IBD Fellow, Box Hill Hospital, Melbourne• IBD Researcher, Christchurch• Nutrition Support Fellowship, St Mark’s, London
![Page 3: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/3.jpg)
Acknowledgements
• Brian Poole
• Pharmaco / Ferring• Pharmaco / Ferring– Distributers of Pentasa
![Page 4: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/4.jpg)
Conflicts of Interest
• I have received support to present research at international meetings from– Ferring/Pharmaco– Ferring/Pharmaco– Pharmatel Fresenius Kabi– Schering Plough– Abbott– Orphan
![Page 5: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/5.jpg)
IBD – a selected overview• IBD in NZ
– A New Epidemic?
• What Causes IBD?– Insights from your backyard– Insights from your backyard
• Drug Treatment of IBD– The battle to get and keep you well
• Diet and IBD– Are you what you eat?
![Page 6: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/6.jpg)
IBD in New Zealand
A new epidemic?
Department Of Gastroenterology, Christchurch Hospital
![Page 7: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/7.jpg)
Overview
• What is IBD• Things that can get mixed up with IBD• IBD International• IBD International• IBD in NZ (the past)• IBD in NZ (now)• What does the future hold?
![Page 8: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/8.jpg)
Overview
• What is IBD• Things that can get mixed up with IBD• IBD International• IBD International• IBD in NZ (the past)• IBD in NZ (now)• What does the future hold?
![Page 9: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/9.jpg)
Inflammatory Bowel Disease
Crohn’s disease Ulcerative Colitis
Indeterminate colitis
![Page 10: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/10.jpg)
The Gastrointestinal Tract
Ulcerative ColitisColon only
Crohn’s diseaseAny part of the GI tract
Continuous inflammation
Inflammation starts at the bottom and moves proximally
Inflammation affects inner lining of bowel only (mucosa)
Patchy inflammation
Inflammation affects full thickness of intestine
Perianal disease
![Page 11: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/11.jpg)
Normal Colon
![Page 12: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/12.jpg)
Inflammatory Bowel Disease
Abdominal Pain
DiarrhoeaMedication/
Surgery
Weight Loss
Diarrhoea
Rectal Bleeding
Colorectal Cancer
Surgery
![Page 13: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/13.jpg)
Normal v IBD
Why?Why?
![Page 14: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/14.jpg)
Overview
• What is IBD• Things that can get mixed up with IBD• IBD International• IBD International• IBD in NZ (the past)• IBD in NZ (now)• What does the future hold?
![Page 15: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/15.jpg)
IBD Differential Diagnosis
Other causes of GI Sx• Irritable Bowel
Syndrome (IBS)
Other causes of Inflammation• Infective gastroenteritis• Drugs (NSAIDS)
• Colorectal Cancer• Diverticular disease• Microscopic colitis• Coeliac disease
• Drugs (NSAIDS)• IBD
– Crohn’s disease– Ulcerative colitis
![Page 16: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/16.jpg)
Overview
• What is IBD• Things that can get mixed up with IBD• IBD International• IBD International• IBD in NZ (the past)• IBD in NZ (now)• What does the future hold?
![Page 17: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/17.jpg)
![Page 18: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/18.jpg)
IntroductionIBD epidemiology
2.5
5.0
7.5
10.0
12.5
15.0
17.5UppsalaFlorenceOrebroIcelandCopenhagenOlmstedStockholmCardiff
Inci
denc
e (/
100
000)
2
4
6
8
10 CardiffCentral SwedenCopenhagenDerbyFlorenceIcelandNE ScotlandOlmstedC
D in
cide
nce
(/10
0 00
0)
Figure 1.1BIncidence of UC in various regions
1950 1960 1970 1980 19900.0
2.5 Cardiff
Year
The incidence of IBD has risen rapidly over the last 50 years
Figure 1.1AIncidence of CD in various regions
1940 1950 1960 1970 1980 19900
OlmstedOrebroStockholmUppsalaYear
CD
inci
denc
e (/
100
000)
![Page 19: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/19.jpg)
Overview
• What is IBD• Things that can get mixed up with IBD• IBD International• IBD International• IBD in NZ (the past)• IBD in NZ (now)• What does the future hold?
![Page 20: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/20.jpg)
Epidemiological studies of IBD in New Zealand
• Wigley, et al., 1962 Wellington
• Eason, et al., 1982
• Schlup, et al., 1986
Auckland
Otago
![Page 21: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/21.jpg)
Epidemiological studies of IBD in New Zealand
Wellington1962
Auckland1982
Otago1986
UC is about as common as other placesCD is less common than other places
Very few Maori / Pacific Island people have IBD
1962 1982 1986
![Page 22: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/22.jpg)
Introductionthe reality in Christchurch
• clinics full of IBD patients
• most clinically difficult group of patients
• � use of expensive tests/therapies
• CD >> UC
• little understanding of aetiology
![Page 23: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/23.jpg)
How common is IBD in Canterbury?
• Try to find every person living in Canterbury ever diagnosed with IBD
= Prevalence• Try to find every person living in
Canterbury diagnosed with IBD in 2004
= Prevalence
= Incidence
![Page 24: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/24.jpg)
MethodsCase recruitment and prevalence study
Outpatientclinics
InpatientsClinicalinformation
The Canterbury IBD Study
Epidemiology
SupportGroups
Advertising
DirectMail
Serum
Environmentalinformation
DNA
Genetic studies
Environmental risk factors
Drug studies
Role of microbes
Effect on people
![Page 25: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/25.jpg)
Canterbury
464 700 people (2005)
75% live in Christchurch
10% of NZ population10% of NZ population
Centralised health services
Good public/private health relationships
![Page 26: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/26.jpg)
Canterbury, New Zealand
![Page 27: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/27.jpg)
Incidence of IBD in Canterbury (2004)
– Previous highest published 14.6/100 000
CD 16.5 / 100 000
– Previous highest published 14.6/100 000 (Manitoba, Canada - 1994)
– About average compared to other populations
UC 7.6 / 100 000
![Page 28: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/28.jpg)
Worldwide incidence of CD
10
15
20CardiffCentral SwedenCopenhagenDerby
CD
inci
denc
e (/
100
000)
Figure 1.1AIncidence of CD in various regions
1940 1950 1960 1970 1980 1990 20000
5
10 FlorenceIcelandNE ScotlandOlmstedOrebroStockholmUppsalaCanterbury
Year
CD
inci
denc
e (/
100
000)
![Page 29: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/29.jpg)
Worldwide incidence of UC
10.0
12.5
15.0
17.5UppsalaFlorenceOrebroIceland
Inci
denc
e (/
100
000)
Figure 1.1BIncidence of UC in various regions
1950 1960 1970 1980 1990 20000.0
2.5
5.0
7.5
10.0 IcelandCopenhagenOlmstedStockholmCardiffCanterbury
Year
Inci
denc
e (/
100
000)
![Page 30: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/30.jpg)
Prevalence of IBD in Canterbury
Crohn’s disease715
Ulcerative colitisUlcerative colitis680
IBD total1420
![Page 31: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/31.jpg)
Prevalence of IBD in Canterbury
Crohn’s disease715
155 / 100 000
Ulcerative colitis 145 / 100 000Ulcerative colitis680
145 / 100 000
IBD total1420
308 / 100 000
![Page 32: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/32.jpg)
World-wide prevalence of IBD
(/100 000 population)
Location Year CD UC
Canada (Mannitoba)Canterbury (NZ)Britain (Aberdeen)Sweden (Orebro)USA (Minnesota)Germany (Tubingen)Denmark (Copenhagen)
1984200419881987199119941987
1991551471361335554
170145-23422925161Denmark (Copenhagen)
Hungary (Veszprem)Israel (Jews – southern)Netherlands (Leiden)Italy (Florence)Faroe IslandsIceland (Nation-wide)Spain (Granada)Puerto Rico (South-west)India (Punjab)
1987200119921983199219881979198920002000
5453514840321096-
161143--121157122211344
![Page 33: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/33.jpg)
CD age of diagnosis
50
60
70
80
MaleFemale
Num
ber
of C
D p
atie
nts
Figure 2.5ACD age of diagnosis by sex
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90
0
10
20
30
40
50 Female
Age of diagnosis
Num
ber
of C
D p
atie
nts
![Page 34: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/34.jpg)
UC age of diagnosis
30
40
50MaleFemale
Num
ber
of U
C P
atie
nts
Figure 2.5BUC Age of Diagnosis by Sex
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95
0
10
20
Age of UC Diagnosis
Num
ber
of U
C P
atie
nts
![Page 35: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/35.jpg)
IBD gender splitCrohn’s disease Ulcerative colitis
59%
p = 0.042
FemaleMale 49%
p = ns
![Page 36: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/36.jpg)
How common is IBD in Canterbury?
• In 2004, Canterbury had the highest rate of newly diagnosed CD ever recorded
• There is more CD than UC in Canterbury
• Women are more likely than men to get CD
• People are often diagnosed when young
• IBD - uncommon in Maori / rare in Pacific Islanders
• More medical services will be needed to treat people with IBD
![Page 37: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/37.jpg)
IBD in New Zealanda new epidemic?
ep·i·dem·ic ( p -d m k) or ep·i·dem·i·cal (- -k l)adj.
– Spreading rapidly and extensively by infection and affecting many individuals in an area or a population at
– Spreading rapidly and extensively by infection and affecting many individuals in an area or a population at the same time, as of a disease or illness.
n.– An outbreak or unusually high occurrence of a disease or
illness in a population or area.
The American Heritage® Stedman's Medical DictionaryCopyright © 2002, 2001, 1995 by Houghton Mifflin Company. Published by Houghton Mifflin Company
![Page 38: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/38.jpg)
What causes IBD?
Department Of Gastroenterology, Christchurch Hospital
Insights from your backyard
![Page 39: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/39.jpg)
What causes IBD?Insights from your backyard
• Genes
• The “coal face”• The “coal face”
• The environment – the forgotten factor
![Page 40: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/40.jpg)
Current concepts of IBD
Genetic Susceptibilty
Host Immune
Response
EnvironmentalFactors
![Page 41: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/41.jpg)
IBD and Genes
If you have IBD, you are 5-10x more likely than someone without IBD to have an
Genesaffected first degree relative
If you are an identical twin with Crohn’s disease, your twin has a 50% chance of
having Crohn’s disease as well
Are
Important
![Page 42: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/42.jpg)
How much genetic information does each of us contain?
• 60,000 genes in the human genome
• 2 metres of DNA in every cell
• many aspects of bodily function require multiple genes
![Page 43: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/43.jpg)
So what are genes?
• Our individual blueprint• The instructions needed to make proteins
– Building blocks– Building blocks– Enzymes– Receptors– Cytokines– ………
![Page 44: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/44.jpg)
IBD and Bacteria
• Immune system identifies and eliminates
foreign organisms and particles
• We are 1% human, 99% bacterial!
• Symbiotic relationship (immune tolerance)
• Dysregulation exacerbates inflammation
![Page 45: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/45.jpg)
IBD Pathogenesis
Intestine Body
Interaction NOD2
With
Immune
System
IL23R
ATG16LTLR4
DLG5
NCF4
![Page 46: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/46.jpg)
NOD2 mutations occur more frequently in some types of CD…
• Stricture (narrowing) 2x ����
• Ileal disease location 3x ����
• Bowel resection surgery 4x ����
• Relative with IBD 1.5x ����
• Diagnosed <17 years 2x ����
![Page 47: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/47.jpg)
IntroductionIBD epidemiology
2.5
5.0
7.5
10.0
12.5
15.0
17.5UppsalaFlorenceOrebroIcelandCopenhagenOlmstedStockholmCardiff
Inci
denc
e (/
100
000)
2
4
6
8
10 CardiffCentral SwedenCopenhagenDerbyFlorenceIcelandNE ScotlandOlmstedC
D in
cide
nce
(/10
0 00
0)
Figure 1.1BIncidence of UC in various regions
1950 1960 1970 1980 19900.0
2.5 Cardiff
Year
The incidence of IBD has risen rapidly over the last 50 years
Figure 1.1AIncidence of CD in various regions
1940 1950 1960 1970 1980 19900
OlmstedOrebroStockholmUppsalaYear
CD
inci
denc
e (/
100
000)
![Page 48: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/48.jpg)
The environment and IBD
• Genes cannot explain the rapid increase in IBD
• Rapid changes in disease incidence ==
Changes in environmental factors
“Genes may load the gun, but the environment pulls the trigger”
![Page 49: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/49.jpg)
Case-control study
Odds ratio 4/2
People with medical condition
People without medical condition
Odds ratio 4/2
= 2.0
![Page 50: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/50.jpg)
Case-control study
Odds ratio 2/4
People with medical condition
People without medical condition
Odds ratio 2/4
= 0.5
![Page 51: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/51.jpg)
Smoking and IBD
2
3
Odd
s ra
tio
Increased Risk
0
1
Crohn's disease Ulcerative colitis Ulcerative colitis
Odd
s ra
tio
Decreased Risk
Smoker at diagnosis Ex-smoker at diagnosisSmoker at diagnosis
![Page 52: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/52.jpg)
Maternal smoking and IBD
2
3
Odd
s ra
tio
Increased Risk
0
1
Crohn's disease Ulcerative colitis
Odd
s ra
tio
Decreased Risk
![Page 53: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/53.jpg)
Family history and IBD
6
8
10
12
14
Odd
s ra
tio
Increased Risk
0
2
4
6
Crohn'sdisease
Ulcerativecolitis
Crohn'sdisease
Ulcerativecolitis
Odd
s ra
tio
Decreased Risk
One relative with IBD Two relatives with IBD
![Page 54: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/54.jpg)
Duration of Breastfeeding & risk of CD
1.0
1.5
Odd
s ra
tio
(95%
CI)
Increased Risk
0 0-2 3-6 6-12 >120.0
0.5
1.0
Duration of breast-feeding (months)
Odd
s ra
tio
(95%
CI)
Decreased Risk
![Page 55: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/55.jpg)
Duration of Breastfeeding & risk of UC
1.5
2.0
Odd
s ra
tio
(95%
CI) Increased Risk
0 0-2 3-6 6-12 >120.0
0.5
1.0
Duration of breastfeeding (months)
Odd
s ra
tio
(95%
CI)
Decreased Risk
![Page 56: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/56.jpg)
Environmental risk factors & CDRisk Factor OR 95%CI
One relative IBDTwo relatives IBDSmoker at diagnosisMaternal smokingAppendicectomyTonsillectomy
3.07.02.01.71.71.5
2.2-4.13.3-151.5-2.71.2-2.31.2-2.01.1-2.0Tonsillectomy
Breastfed as infantOCP useHigh antibiotic use (adolescence)Urban livingChildhood vegetable gardenHigh childhood SESHigh recruitment SES
1.50.51.82.11.50.51.60.5
1.1-2.00.4-0.71.1-3.11.3-3.31.1-2.10.4-0.71.1-2.20.3-0.7
![Page 57: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/57.jpg)
Environmental risk factors & CDRisk Factor OR 95%CI
One relative IBDTwo relatives IBDSmoker at diagnosisMaternal smokingAppendicectomyTonsillectomy
3.07.02.01.71.71.5
2.2-4.13.3-151.5-2.71.2-2.31.2-2.01.1-2.0Tonsillectomy
Breastfed as infantOCP useHigh antibiotic use (adolescence)Urban livingChildhood vegetable gardenHigh childhood SESHigh recruitment SES
1.50.51.82.11.50.51.60.5
1.1-2.00.4-0.71.1-3.11.3-3.31.1-2.10.4-0.71.1-2.20.3-0.7
![Page 58: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/58.jpg)
Environmental risk factors & UC
Risk Factor OR 95%CI
One relative IBD
Two relatives IBD
Smoker at diagnosis
2.5
6.8
0.7
1.8-3.5
3.2-15
0.5-0.9
Ex-smoker at diagnosis
Appendicectomy
Breastfed as infant
High antibiotic use (adolescence)
Childhood vege garden
Childhood SES
1.8
0.4
0.7
1.7
0.6
1.7
1.4-2.4
0.3-0.7
0.5-0.9
1.1-2.8
0.4-0.9
1.2-2.4
![Page 59: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/59.jpg)
Environmental risk factors & UC
Risk Factor OR 95%CI
One relative IBD
Two relatives IBD
Smoker at diagnosis
2.5
6.8
0.7
1.8-3.5
3.2-15
0.5-0.9
Ex-smoker at diagnosis
Appendicectomy
Breastfed as infant
High antibiotic use (adolescence)
Childhood vege garden
Childhood SES
1.8
0.4
0.7
1.7
0.6
1.7
1.4-2.4
0.3-0.7
0.5-0.9
1.1-2.8
0.4-0.9
1.2-2.4
![Page 60: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/60.jpg)
Do environmental factors play an important role in IBD?
• Environmental factors are very important
• Some environmental factors may be modifiable• Some environmental factors may be modifiable
• Associations give us clues as to why IBD occurs
• Many risk factors may occur in infancy / childhood
![Page 61: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/61.jpg)
Causes of IBD are Multifactorial
1 2 3 4
![Page 62: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/62.jpg)
The effect of IBD
• Important to measure the effects of disease
– Resource allocation– Resource allocation• New treatments• Medical /nursing staff• Community support
– Prognostic information for patients
![Page 63: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/63.jpg)
The effects of IBD (1)
25
30
35
40
45
0
5
10
15
20
25
Control CD UC
%
Does a health problem or condition you have (>6 months) cause you difficulty with or stop doing everyday activities that people you age
can usually do?
![Page 64: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/64.jpg)
Average number of days away from usual activities
15
20
25
Days
0
5
10
Control CD UC
Days
![Page 65: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/65.jpg)
The Canterbury IBD StudyConclusions
• IBD is not rare in Canterbury; CD is very common• IBD in Canterbury is similar to elsewhere• Genes are important – but not the whole story• Genes are important – but not the whole story• Environment is important – but difficult to unravel• IBD has a significant impact on the lives of many
Cantabrians• The Canterbury IBD Study provides a unique tool
for ongoing population-based research
![Page 66: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/66.jpg)
Drug Treatment of IBD
the battle to get and keep you well
Department Of Gastroenterology, Christchurch Hospital
the battle to get and keep you well
![Page 67: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/67.jpg)
Overview
• Treatment for IBD• Medical treatment for IBD• Medical treatment for severe IBD• Medical treatment for severe IBD• Remicade (Infliximab)• Humira (Adalimumab)• Costs and implications• Future directions• ACCA document
![Page 68: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/68.jpg)
Treatment for IBD
Drugs CAMs Stress
Surgery
Diet
Knowledge Lifestyle
Support
![Page 69: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/69.jpg)
Medical Treatment for IBDDisease flare
Biologicals
Immunomodulaters (Azathioprine. 6-MP,
Methotrexate)
Steroids
5-ASAs(Sulfasalazine, Pentasa, Asacol)
![Page 70: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/70.jpg)
Medical Treatment for IBDMaintenance of remission
Biologicals
No role for long term steroids in maintaining Biologicals
Immunomodulaters (Azathioprine. 6-MP, Methotrexate)
5-ASAs(Sulfasalazine, Pentasa, Asacol)
in maintaining remission in IBD
![Page 71: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/71.jpg)
Medical treatment for severe IBD(requiring admission to hospital)
Intravenous steroids (5-7 days given 6 or 8 hourly)
Biological Agents (Remicade / Humira)Biological Agents (Remicade / Humira)
Only for UC - IV Cyclosporin (rarely)
Only for CD Exclusive Enteral Nutrition (paediatric s)
Surgical Opinion
![Page 72: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/72.jpg)
Medical therapy for IBD
Treatment UC CD
relapse remission relapse remission
5-ASA/SSZ
Steroid
Aza/6MP/MTX
Biological Agents
Antibiotics
++++-
+-++-
+++++
+-+++
![Page 73: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/73.jpg)
Biological Therapieswhat are they?
• Designer drugs• Aimed at specific molecules in the inflammatory
cascade• Also known as “MABs” – Monoclonal AntiBodies• New drug - ?long term safety…• At least as effective as anything we have now• Fewer obvious side effects• Very expensive …
![Page 74: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/74.jpg)
Remicade (infliximab)
• Monoclonal antibody to TNF-α– Central cytokine in the inflammatory / immune response
• Given Weeks 0, 2, 8 then 8 weekly• 97% human sequence / 3% mouse sequence• 97% human sequence / 3% mouse sequence• Given as a 2-3 hour infusion• Rapid onset of action• Infection / ? Lymphoma / Allergy
• www.remicade.com
![Page 75: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/75.jpg)
Remicade for Perianal Disease
• 68% v 26% had >50% of fistulas closed• 55% v 13% had all fistulas close• Well-tolerated• Well-tolerated
• But if you stop taking it – they come back!!
![Page 76: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/76.jpg)
Remicade for Luminal CD
• Remission at 4 weeks– 33% v 4%
• Improvement at 4 weeks– 81% v 17%
• Maintenance of remission (1 year)– 39% v 21%
![Page 77: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/77.jpg)
Remicade for UC
![Page 78: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/78.jpg)
Remicade for UC
![Page 79: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/79.jpg)
• Fully human monoclonal antibody (IgG1)– specifically neutralizes TNF-α
• Self-administered sub cut injection• RA / PsA / AS dose
HUMIRA (Adalimumab)
– 40 mg every other week (eow)
• Crohn’s Disease: – Induction 160mg week 0 / 80mg week 2– Maintenance 40 mg eow
• >180,000 patients currently being treated worldwide
![Page 80: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/80.jpg)
CLASSIC I Trial: Results at Week 4
36%
54%59%
37% 34%40%
50%
Sub
ject
s (%
)
*
‡
40
50
60
70
Placebo/placebo Adalimumab 40/20
Adalimumab 80/40 Adalimumab 160/80
59%*†*
•p<0.05; † p=0.003; ‡ p=0.002 Clinical remission=CDAI <150
Clinical response ∆∆∆∆70 or ∆∆∆∆100=CDAI decrease from baseline ≥70 or ≥100
18%
24%
36%
12%
37% 34%
Sub
ject
s (%
)
25%
0
10
20
30
40
Clinical Remission
Response, ∆∆∆∆70
Response, ∆∆∆∆100
![Page 81: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/81.jpg)
CLASSIC I: Treatment-Emergent Serious Adverse Events Summary
Placebon=74
40/20 mg EOWn=74
80/40 mg EOWn=75
160/80 mg EOWn=76n=74 n=74 n=75 n=76
SAE*, n (%) 3 (4) 0 (0) 1 (1) 3 (4)
Serious infections
0 (0) 0 (0) 0 (0) 2 (3)
Perianal abscess
0 (0) 0 (0) 0 (0) 1 (1)
Pneumonia 0 (0) 0 (0) 0 (0) 1 (1)
![Page 82: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/82.jpg)
CHARM Co-Primary End points
Primary Responders
![Page 83: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/83.jpg)
CHARM Secondary End points –steroid weaning
![Page 84: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/84.jpg)
4-week OL n=854
Post randomization (weeks 4–56)
n (%)Placebon=261
40 mg EOWn=535
40 mg weeklyn=410
Infections and infestations* 10 (1.2) 9 (3.4) 16 (3.0) 11 (2.7)
Infectious SAEs of InterestAbscess 7 (0.8) 5 (1.9) 5 (0.9) 6 (1.5)
TB 0 (0.0) 0 (0.0) 1 (0.2) 1 (0.2)
CHARM: SAEs of InterestAll Adalimumab-treated Patients
TB 0 (0.0) 0 (0.0) 1 (0.2) 1 (0.2)
Other opportunistic infections 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
Wound infection, sepsis, post-operative infection 3 (0.4) 0 (0.0) 0 (0.0) 1 (0.2)
Pneumonia 0 (0.0) 0 (0.0) 0 (0.0) 2 (0.5)
Cancer 0 (0.0) 1 (0.4) 0 (0.0) 0 (0.0)
Multiple Sclerosis 1 (0.1) 0 (0.0) 0 (0.0) 0 (0.0)
Serum Sickness 1 (0.1) 0 (0.0) 0 (0.0) 0 (0.0)
Death 1 (0.1) 0 (0.0) 0 (0.0) 0 (0.0)
Colombel JF, et al. T686d, DDW 2006; data on file.
![Page 85: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/85.jpg)
GAIN: Efficacy Outcomes at Week 4
25
3438
52
30
40
50
60
PBO 160/80 mg
*
% o
f Pat
ient
s
*†
25
7
21
0
10
20
30
Remission Response CR-70 Response CR-100
*
*P<0.001, †P<0.01, both vs. placebo.
% o
f Pat
ient
s
34/159 56/166 82/159 41/166 61/15912/166
Sandborn WJ, et al. Ann Intern Med. 2007;146(12).
![Page 86: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/86.jpg)
Outside the square• Children
– Remicade• Used effectively• Safety data• Clinical trial data• Clinical trial data
• Pregnancy– Remicade
• Contraindicated• Pregnancy may occur on the drug
• Breastfeeding– Remicade
• Not advised
![Page 87: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/87.jpg)
Costs and Implications
• These drugs only work if you keep taking them– Need to have a viable alternative option – Need to have a viable alternative option
in the future (eg azathioprine or methotrexate)
– No other alternative available (including surgery)
• Long term safety data are lacking
![Page 88: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/88.jpg)
Costs and Implications
• Remicade cost $1175/ 100mg vial– 5mg/kg is the standard dose– 5 X 60kg = 300mg ($3525/dose)– 3 X induction doses then 8 weekly = $31725 per year– 3 X induction doses only = $10575
• Humira cost $900/ 40mg injection– 160mg / 80mg / 40mg eow– 3 X induction doses then 40mg fortnightly = $27000 per year– 3 X induction doses only = $6300
![Page 89: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/89.jpg)
Costs and Implications
• Current use at Christchurch Hospital
• Remicade– July-Sept 2005 $70500– July-Sept 2006 $185395– July-Sept 2007 …
• No Humira data as yet
![Page 90: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/90.jpg)
ImplicationsCanterbury IBD incidence (2004)
1940 1950 1960 1970 1980 1990 20000
5
10
15
20
Year
CD
inci
denc
e (/
100
000)Inflammatory bowel disease
25.2 / 100 000
Crohn’s disease
16.5 CROHN'S DISEASE
Year
ULCERATIVE COLITIS
1950 1960 1970 1980 1990 20000.0
2.5
5.0
7.5
10.0
12.5
15.0
17.5
Year
Inci
denc
e (/
100
000)
16.5 / 100 000
Ulcerative colitis
7.6 / 100 000
Indeterminate colitis
1.1 / 100 000 Gearry et al, Inflammatory Bowel Diseases, 2006
![Page 91: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/91.jpg)
ImplicationsSex and age of onset
0
10
20
30
40
50
60
70
80
MaleFemale
Num
ber
of C
D p
atie
nts
Crohn’s DiseaseFemale > Male (p=0.042)
Peak age onset ~25 years
Second peak ~55 years
Median age onset 29.5 yearsCROHN'S DISEASE
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90
0
Age of diagnosis
ULCERATIVE COLITIS
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95
0
10
20
30
40
50MaleFemale
Age of UC Diagnosis
Num
ber
of U
C P
atie
nts
Median age onset 29.5 years
Ulcerative colitisMale > Female (ns)
Peak age onset ~30 years
Median age onset ~36.5 years
![Page 92: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/92.jpg)
Future directions• New Mabs mean competition• Competition lowers price
• Lobbying Pharmac / Politicians• NZSG / Gastroenterologists / Patients
• Signalling high cost to hospital managers
![Page 93: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/93.jpg)
Key Messages• Mabs are not magic bullets• Long term safety data is lacking• Effective alternative in specific situations• Effective alternative in specific situations• Costs are high• National disparity in access• Pressure on Pharmac and Politicians• Joint approach is advocated
![Page 94: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/94.jpg)
ACCA IBD Document• Economic cost of IBD = $2.7 billion (includes a financial cost
of $500 million + net cost of lost wellbeing $2.2 billion)
• Lost productivity accounts for > half cost ($266.7 million)
• Estimated cost of absenteeism for IBD patients = $52.3 million• Estimated cost of absenteeism for IBD patients = $52.3 million
• Costs to the health system = $79 million
• 939,000 hours of informal care provided to IBD patients ($23.5 million)
• Estimated out of pocket expenses for IBD patients = $35.8 million
www.acca.net.au (media page)
![Page 95: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/95.jpg)
IBD Drug Treatment Summary
• UC – 5ASA is the best option
• CD – less evidence for 5-ASA• CD – less evidence for 5-ASA
• CD – immunomodulators key for maintenance
• Steroids – no long term role
• Biologicals – the missing link
![Page 96: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/96.jpg)
Canterbury IBD Studyresearch team
Gastroenterology• Murray Barclay• Bruce Chapman• Michael Burt• Judith Collett• James Yeo
Epidemiology / Statistics• Ann Richardson• Chris Frampton
Research Assistants• Judy Hoar• James Yeo • Judy Hoar• Rhondda Brown• Pip Shirley• Ramez Ailabouni• Andrew Dodgshun• Megan Reilly• Charlotte Duncan• David Tan
Gene Structure & Function Lab• Martin Kennedy• Rebecca Roberts• Nick Bockett• Melanie Allington• Aliison Miller
![Page 97: Inflammatory Bowel Disease - Crohns and Colitis NZ...Inflammatory Bowel Disease A selected overview Dr Richard Gearry Department Of Gastroenterology, Christchurch Hospital Senior Lecturer,](https://reader031.fdocuments.net/reader031/viewer/2022041110/5f1061227e708231d448d206/html5/thumbnails/97.jpg)