Post on 07-Aug-2020
Natural History of IBD=
Inflammatory bowel disease
Ulcerative colitis(UC)
Crohn’s disease
Inflam bowel disease unclassified(IBDU)
Are the definitions of MH reproducible?
- On an individual or group level
Localisation of Crohn’s disease
Classification of CD at inclusion in the IBSEN study (1990 – 1994)
L1, terminal ileum: 64L2, colon: 115L3, ileocolon: 54L4, upper GI: 4 Total: 237
Localisation of inflammation in UC in the IBSEN- study (1990-1994)
Proctitis: 17 Proctosigmoiditis: 101Left sided: 81Total colitis: 166Total: 519
Ulcerative colitis
The frequency of IBD over time
Recording by the IBSEN study
group
BjM, 93
GP
G-1
G-1
1 year
G 2 PL
Communication
Incidence according to age and
genderUC / IBDU CD
Moum B et al, Scand J Gastroenterol; 1996;31:362-66Moum B et al, Scand J Gastroenterol; 1996;31:355-61
20-35 år 15-25 år
Incidence of CD
2.7(1990-93)
6.7(2005-07)
2.8(1993-04)
1.9(1987-03)
4.9(1990-01)
2.5(1984-85)
3.1(1998-06)
Ref. Table 2
Fig. 3
IBD Incidence 0-16 years
0
2
4
6
8
10
12
In
cid
en
ce
/1
00
00
0/
ye
ar
CD UC IBDU total IBD
CD 2,7 1,9 3,6 6,7
UC 2 3,7 2,1 3,3
IBDU 0 0 0 0,7
total IBD 4,7 5,6 5,7 10,6
IBSEN 1990-93 Ahus 1994-98 Ahus 1999-04 IBSEN-II 2005-07
Incidence 0-16 years
Incidence of CD
2.5(1981-95)
2.2(1980-90)4.4(1990-99)
3.1(1998-99)
0.25(1990-99)1.25(1999-2001)
3.6(1996-2003)
2.1(1999-2001)2.3(1988-99)
8.5(1990-94)
1.4(1996-97)
Ref. Table 3
Fig. 4
Incidence of IBD in Europe - adults
32
24
2221
12
6 14
11
4
14
14
12
9
45
8
17
8 8
5
13
11
11
14
11
211.5
20 1919
16
11
29
22
4
20
19
Fig. 7
7.5
4.2
8.4
20
20
14.4
6.5
0
4.8
11.4
5.9
6.1
2.63.7
Incidence of IBD in the USFig. 6
Fig.5
20
30
40
5
4
12
6
5.5
4.5
2.2
5.5
19
12.5
5
2.5
2
32
6
1.5
6
24
Global incidence of IBD
Balance between the bacterial-flora of the gut and a dysfunctional immune-system in a genetically disposed host
Patogenesis of IBD
12.5
7.2 5.5
4.3 4.5
3.3
127.2
8.8
16
9.7
11.5
12.2
6.8
0
10
15.1
Etnicity and NOD2 mutations
The frequency of CARD15 (R702W) in Crohns Disease in European countries
GENETICS and IBD
• Having a family member with IBD represents the strongest risc factor (”dose respons effekt”)– First degree relative with IBD gives approx. 15% risc
• λs-”relative sibling risc” – (Crohn: 20-35, Ulcerative Colitis: 6-9)
• Twin studies:– Monozygotic twins risc vs dizygotic
• Crohn 35% vs dizygotic 7%
• Ulcerative Colitis 11% vs dizygotic 3%
NOD2/CARD15OCTN1/2ATG16LIL23R
Zahng et al, Br Med Bulletin, 2008;87, Rosenstiel et al, Sem Immunology 2009;21
The Hygiene hypothesis
The theory of reduced diversity of bakterial
stimulation as an explanation for increased allergic
and immunologic diseases
Faktors influencing our bakterial flora:
• Modern lifestyle
• Food consumption (milk- and meat products) and
industrialisation of food products
• Antibiotics
• Birth release
Environmental factors
• Smoking gives increased risc for
CD, but ”protects” against UC
• Breast feeding >3 mnd gives reduced
risc for IBD (bifidobact , anaerobe bact
)
• Antibiotics early in life may give
increased risc for IBD
Gearry et al,J Gastroent Hepatol,2010;25
Drinking water and IBD
• Analysis of drinkingwater and occurrence
of IBD showed:
By increase of iron concentration in
drinking
water by 0.1mg/L, the relative risc for
development of IBD increased by 21%
– Iron catalysis oksidativt stress
(inflammasjon and cell mutation)
– Iron stimulates bacterial growth (influence
on epithelial cell barrier and immune
response)
Aamodt et al, Am J Epidemiol,2008;168
Disease behaviour of IBD within
a region
Cum
ulati
ve
prob
abilit
y of
first
surg
ery
Years after diagnosis of CD
40 %
60 %
80 %
100 %
20 %
0 %
Risk factors for surgery in CDSolberg IC et al. Clin.Gastroenterol Hepatol. 2007;5:1430-38.
11109876543210
Time in years since diagnosis
1,0
0,8
0,6
0,4
0,2
0,0
Cu
mu
lati
ve
ha
zard A2 (>40 yrs)
A1 (<40 yrs)
Age
One Minus Survival Function for patterns 1 - 211109876543210
Time in years since diagnosis
1,0
0,8
0,6
0,4
0,2
0,0
Cu
mu
lati
ve h
azard
Ileocolonic (L3)
Colonic (L2)
Small bowel (L1 or L4)
Disease location
One Minus Survival Function for patterns 1 - 3
11109876543210
Time in years since diagnosis
1,0
0,8
0,6
0,4
0,2
0,0
Cu
mu
lati
ve h
azard
B3: Penetrating
B2: Stricturing
B1: Pure inflammatory
Disease behaviour
One Minus Survival Function for patterns 1 - 3
Non significant
variables
Gender
Smoking status,
Familial IBD,
Systemic steroids
P = 0.03
P = 0.001
P = 0.001
11109876543210
Time in years since diagnosis
1,0
0,8
0,6
0,4
0,2
0,0
Cu
mu
lati
ve
ris
k o
f in
testi
na
l re
secto
in
One Minus Survival Function
13.6%
27.0%
37.9%
N = 237
E = 85 65%
34%
23%
IBSEN study: Disease course during
the first 10-year period, patients’ perceptive
CD 43%
CD 19% CD 37%
CD 3%
Remission rate(grey) during the
first and second 5 years period
of CD
(50)(4)(94)(N) (148) (49) (51) (94) (48) (4) (127) (50)
p = 0.7p = 0.2
I. First 5-years
period
p = 0.8p = 0.9p = 0.08
85
15
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
B1
78
22
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
A2
49
51
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
L2
83
17
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
L2
87
13
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
L3
100
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
L4
85
15
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
B1
84
16
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
B2
90
10
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
B3
61
39
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
A1
43
57
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
A2
57
43
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
L1
49
51
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
L2
69
31
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
L3
75
25
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
L4
54
46
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
B1
64
36
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
B2
55
45
0 %
10 %
20 %
30 %
40 %
50 %
60 %
70 %
80 %
90 %
100 %
B3
p = 0.03 *
(20) (N) (148) (49) (51) (48) (127) (20)
II. Second 5-years period
Figure V. Cumulative drug consumption (after initial treatment) in CD patients during the first 5 years period
(patterned bars) vs. the second 5 years period (grey bars) (): = percentage of total number (N)
0
20
40
60
80
100
120
140
160
180
200
First 5-year
Second 5-year
5-ASA Systemic
steroids
Azathioprine TNF-blocker
175(88)
125(64)
143(73)
82(42)
42(21)51(26)
8(4)
p<0.001
p<0.001
Ns
Num
ber of
patie
nts
treate
d
Conventional treatment in IBD:• Combination of general guidelines and individual
experience with a patient
• A close follow up from start of treatment should aim at
detecting intolerance or lack of effect
• Drug therapy should aim at the lowest dose(s) giving relief
of symptoms
• Biologics are the most effective drugs on disease activity
and QoL short term, and anti-metabolites effective long
term, in the complicated patient.
• Documented and experienced
increased efficacy
– an indication of top down
strategy
• Still recommendation of step up
strategy:
– adverse reactions
(hypersensitivity, infections)
– long term complications
(neoplasisia)
– cost benefit (prize,
resources)
The introduction of biologics in
the treatment of IBD
Antimetabolites
Biologics
Steroids
Budesonide
5-ASA/Sasp/
Antibiotics/Local
5-ASA/ SASP/
Antibiotics/ Local
Budesonide
Steroids
Antimetabolites
Biologics
MV-11-01
Gs1
GP
Gs1
Gs2 Pc
C-C
GP Gs2Gs1
Epidemiology of IBD in SE Norway in 1990’s
1 yr
Gs15 yr
Gs110 yr
Diagnose
Rheu
QoL IBD 2TK
Genetics
National registration of IBD
Quartiles of incidences of ulcerative
colitis in the study area
The municipalities in
black represent the
upper quartile etc
USA
Iowa
Germany:
RegensburgSpain:
Gijon
Switzerland
Zurich
Greece:
Athens
Croatia:
Rijeka
Zagreb
Argentina:
Buenos Aires
Uruguay
Monevideo
Israel:
Telaviv
Norway:
Oslo
Czech
Prague
Hungary:
Budapest
Early IBD – International Concortium
USA
Rhode Island
Crete