The Burden of IBD Charles N. Bernstein, MD University of Manitoba IBD Clinical and Research Centre Winnipeg, Manitoba, Canada.

The Burden of IBD

Charles N. Bernstein, MDUniversity of Manitoba

IBD Clinical and Research Centre

Winnipeg, Manitoba, Canada

IBD Database Construction

Persons with at least one IBD contact, 1984-1995 (n=10,541)

Exclude if <3 contactsbeginning prior to 1993(n=5,359)

Distribute consent and demographic questionnaire to current residents. (n=4,514)

Optimize “case definitions”versus self-reported diagnosis

Analyze medical contact patternsfor questionnaire respondents.(n=2,725)

“Crohn’s disease”(n=1,230)

“Ulcerative colitis”(n=1,222)

“No IBD”(n=273)

Evaluate “case definitions”versus random charts (n=448)

Apply case definitions toentire health database

60%

Bernstein Am J Epidemiol 1999

Case Definitions: Crohn’s Disease and UC

• At least 5 separate hospital/physician contacts with a diagnosis between 1984 and 1995.

OR

• If registered with Manitoba Health for <2 years, at least 3 separate hospital/physician contacts with a diagnosis.

• If both CD and UC criteria were met, then the majority diagnosis of the most recent 9 contacts was used.

• Diagnosis date is the first hospital/physician contact (applied only to first contacts beginning in 1988 or later).

Time Trends

Crohn’s disease prevalence and incidence, Manitoba,

1990 - 2001, cases/100,000, age standardized to the 1996 Manitoba population

165178

190199 208 217 225

237249 256 262 270

15.2 15.9 14.5 14.6 13.9 12.6 14.9 18.2 16.6 12.6 15.1 13.70

50

100

150

200

250

300

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

143155 163

173188

199 208 216 223 231 236 241

16.2 13.4 13.6 17.8 18.2 15.2 12.6 14.3 15.3 14.1 13.8 10.50

50

100

150

200

250

300

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

UC prevalence and incidence, Manitoba, 1990 - 2001, cases/100,000

age standardized to the 1996 Manitoba population

Annual Age-Adjusted Prevalence of CD and UC,

by First Nation (FN) Status, Manitoba.

0

50

100

150

200

250

1987 1988 1989 1990 1991 1992 1993 1994

Pre

vale

nce

per

100

,000

Non-FN CD

Non-FN UC

FN UC

FN CD

176

14

57

209

Blanchard Am J Epidemiol 2001

M

BM

B

BCAB

SKNS

Age-specific incidence of Crohn’s Disease: by Province

05

1015202530354045

<10 10-19

20-29

30-39

40-49

50-59

60-69

70-79

80+

Age Group

Inci

den

ce p

er 1

00,0

00

BC

AB

SASK

MB

NS

Bernstein AJGI 2005

Age-specific incidence of UC: by Province (1998-2000)

0

5

10

15

20

25

30

35

<10 10-19

20-29

30-39

40-49

50-59

60-69

70-79

80+

Age Group

Inci

den

ce p

er 1

00,0

00

BC

AB

SASK

MB

NS

Bernstein AJGI 2005

Age-specific prevalence of Crohn’s Disease: by Province

(2000)

0

100

200

300

400

500

600

<10 10-19

20-29

30-39

40-49

50-59

60-69

70-79

80+

Age Group

Cas

es p

er 1

00,0

00

BC

AB

SASK

MB

NS

Bernstein AJGI 2005

Age-specific prevalence of UC: by Province (2000)

050

100150200250300350400450

<10 10-19

20-29

30-39

40-49

50-59

60-69

70-79

80+

Age Group

Cas

es p

er 1

00,0

00 BC

AB

SASK

MB

NS

Bernstein AJGI 2005

Population = 30,750,087

Prevalence of Crohn’s disease: 85,854

Prevalence of UC: 64,975

Total IBD: 150,829

?2005: 170,000

Projected prevalence of IBD in Canada in 2000

• MB rates similar to elsewhere in Canada

• Low rates of Crohn’s disease in BC; 22% visible minorities

• High rates of both Crohn’s & UC in Canada;

?North-South gradient

Place - Geographic Distribution

Published Estimates of the Incidence of Crohn’s Disease from

Around the World

0

2

4

6

8

10

12

14

16

Nor 83-

86

Swe 78

-87

Den 7

9-87

UK Car

diff 8

1-85

Neth 8

8-92

N Fra

nce 8

8-90 Ger

Ital 7

8-87

Spain 7

9-88

USA, Min

n 84-

93

USA, Bal

t 77-

79

Man

itoba

1988

-96

Inci

den

ce p

er 1

00,0

00

Published Estimates of the Incidence of Ulcerative Colitis from

Around the WorldIn

cid

ence

per

100

,000

No

r 83

-86

Sw

e 78

-87

Den

79-

87

UK

Car

dif

f 81

-85

Net

h 8

8-92

N F

ran

ce 8

8-90

Ger

Ital

78-

87

Sp

ain

79-

88

US

A,M

inn

84-

93

Man

ito

ba

88-9

6

16

141210

8

6

4

2

0

CD Incidence, 1990 - 2001Cases/10,000, Smoothed

An Ecological StudyGreen Am J Epidemiol 2006

Crohn’s disease UC

Females 1.37 (1.24-1.50) 1.11 (1.02-1.2)

Urban 1.29 (1.17-1.41) 1.12 (1.04-1.21)

SESI top1/3 1.77 (1.55-2.02) 1.48 (1.34-1.63)

Non-Aboriginal 6.91 (3.15-15.16) 2.22 (1.71-2.89)

Non-Aboriginal* 5.47 (3.37-8.87) 1.99 (1.55-2.55)

Jewish* 1.52 (1.22-1.89) 1.45 (1.21-1.74)

Non-vis minorities

1.06 (0.92-1.22) 1.23 (1.1-1.39)

Low enteric infect

MS

1.52 (1.31-1.78)

2.90 (2.19-3.85)

1.19 (1.06-1.33)

1.8 (1.49-2.17)

Extraintestinal burden

to the patient

There is approximately 1 DVT-PE / 200 patient-

years

Bernstein Thromb Hemostasis 2001

Venous thrombosis in IBD

Venous thrombosis in IBD

DVT+PE IRR (95% CI)

Crohn’s disease 4.1 (3.21-5.25)

UC 3.04 (2.43-3.8)

All IBD 3.47 (2.94-4.09)

Males 3.11 (2.42-4.00)

Females 3.78 (3.53-4.71)

Bernstein Thromb Hemostasis 2001

Site-specific cancer IRR comparing cohorts with IBD to Site-specific cancer IRR comparing cohorts with IBD to non-IBD cohorts matched by age, gender and postal non-IBD cohorts matched by age, gender and postal

area of residence, Manitoba, Canada, 1984-1997.area of residence, Manitoba, Canada, 1984-1997.

Crohn’s UC Total IBD

Cancer typeIRR

(95% C.I.)IRR

(95% C.I.)IRR

(95% C.I.)

Lymphoma 2.40(1.17-4.97)

1.03 (0.47-2.24)

1.52 (0.90-2.57)

Hodgkin’s Undefined Undefined Undefined

Leukemia/Other

0.79 (0.24-2.54)

1.02 (0.37-2.86)

0.91(0.42-1.96)

Bernstein Cancer 2001

Other cancer risk ratesCrohn’s disease UC Total IBD

Cancer type IRR(95% C.I.)

IRR(95% C.I.)

IRR(95% C.I.)

Colon 2.64(1.69-4.12)

2.75(1.91-3.97)

2.71(2.04-3.59)

Rectum 1.08(0.43-2.70)

1.90(1.05-3.43)

1.56(0.95-2.57)

Small Bowel 17.4(4.16-72.9)

Undefined 10.4(3.02-36.1)

Hepatobiliary 5.22(0.96-28.5)

3.96(1.05-3.43)

4.38(1.54-12.4)

Bernstein Cancer 2001

Colon cancer population under 50 yrs Colon cancer population 50 yrs + older

Rectal cancer population under 50 yrs Rectal cancer population 50 yrs + older

Age-specific rates of selected comorbidity in IBD and non-IBD hospitalized population, 1994/95-2002/03

Rate per 100,000

**

*

0

50

100

150

200

250

300

1994/95 1995/96 1996/97 1997/98 1998/99 1999/00 2000/01 2001/02 2002/03

IBD Non-IBD

Rate per 100,000

0

100

200

300

400

500

1994/95 1995/96 1996/97 1997/98 1998/99 1999/00 2000/01 2001/02 2002/03

IBD Non-IBD

Rate per 100,000

******

0

100

200

300

400

500

1994/95 1995/96 1996/97 1997/98 1998/99 1999/00 2000/01 2001/02 2002/03

IBD Non-IBD

Rate per 100,000

0

50

100

150

200

250

300

1994/95 1995/96 1996/97 1997/98 1998/99 1999/00 2000/01 2001/02 2002/03

IBD Non-IBD

* The rate is significantly higher in IBD compared to non-IBD cases, p<0.05.

Pulmonary emboli population under 50 yrs Pulmonary emboli population 50 yrs + older

DVT population under 50 yrs DVT population 50 yrs + older

Rate per 100,000

0

100

200

300

400

1994/95 1995/96 1996/97 1997/98 1998/99 1999/00 2000/01 2001/02 2002/03

IBD Non-IBD

Rate per 100,000

0

100

200

300

400

1994

/95

1995

/96

1996

/97

1997

/98

1998

/99

1999

/00

2000

/01

2001

/02

2002

/03

IBD Non-IBD

Rate per 100,000

0150300450600750900

1994

/95

1995

/96

1996

/97

1997

/98

1998

/99

1999

/00

2000

/01

2001

/02

2002

/03

IBD Non-IBD

Rate per 100,000

0150300450

600750900

1994/95 1995/96 1996/97 1997/98 1998/99 1999/00 2000/01 2001/02 2002/03

IBD Non-IBD

There is approximately 1 fracture/100 patient-

years

Bernstein Ann Intern Med 2000

Incidence rate ratios of All fractures comparing IBD to matched population-

based non-IBD cohorts

Crohn’sIRR

UCIRR

All IBDIRR

0-39 yrs 1.37 1.38 1.37(1.10-1.69)

40-59 yrs 1.27 1.60 1.44(1.17-1.76)

60+ yrs 1.41 1.41 1.41(1.21-1.64)

Total 1.36(1.17-1.59)

1.45(1.26-1.67)

1.41(1.27-1.56)

A positive association between chronic inflammatory diseases with either form of IBD could suggest

• common genetic predisposition

• common etiologic triggers,

• or possibly the triggering of one inflammatory condition secondary to Rx of a primary inflammatory condition.

Am J Gastroenterol 2001Gastroenterology 2005

• Since the specificity of a single contact of any of these conditions is not known we analyzed the data for having

at least 5 health system contacts.

The precedent for this in Manitoba:

• Ulcerative colitis

• Crohn’s disease

• Multiple sclerosis

Manitoba: 6.2% have a single extraintestinal disease (exclusive of arthritis)(0.3% have >1 extraintestinal disease)

Sweden (UC): 6-12% (CD): <12%(includes abnormal liver tests)

UC Crohn’s

Uveitis 1.6% 1%

PSC 3.7% <10%

Ank Spond 1.6% 2.2%

PG 0.8% 0.6%

E. nodosum 2.6% 1.9%

Period Prevalence of comorbid diagnoses in UC Disease Controls UC PR (95% CI)

Asthma 4.9% 7.88% 1.66(1.46-1.88)

Bronchitis 0.32% 0.67% 2.10(1.36-3.23)

Arthritis 8.35% 11.77% 1.55(1.39-1.74)

MS 0.29% 0.54% 1.90(1.19-3.03)

Ch Renal Dis 0.16% 0.39% 2.46(1.40-4.35)

Psoriasis 1.04% 1.7% 1.65(1.27-2.15)

Pericarditis 0.07% 0.23% 3.33 (1.57-7.07)

Period Prevalence of comorbid diagnoses in CD Disease Controls CD PR (95% CI)

Asthma 5.1% 7.09% 1.43(1.26-1.62)

Bronchitis 0.26% 0.48% 1.86(1.15-3.02)

Arthritis 6.32% 7.88% 1.24(1.12-1.39)

Psoriasis 1.07% 1.7% 1.59(1.24-2.05)

Pericarditis 0.06% 0.19% 3.07 (1.39-6.78)

Sociological burden

*Health Care Utilization

IBD(n=5756)

Controls(n=66,406)

% Users 91% 77% P<0.05

Mean # Visits 14.4 (0.19) 9.8 (0.05) P<0.05

≤5 25% 41%

6-11 27% 29%

12-23 31% 23% OR=1.50 (1.32 – 1.71)

24+ 17% 7% OR=2.72 (2.24 – 3.30)

OR (95% CI) Visit 3.14 (2.87 – 3.46) P<0.05

OR (95% CI) Surgery

2.82 (2.65 – 3.00) P<0.05

Cross-Sectional StudyIBD vs. Controls: Outpatient Visits

2000-2001

IBD(n=5756)

Controls (n=66,406)

% Users 16% 7% P<0.05

Mean # Days (se) 10.9 (0.85) 10.5 (0.37) not sig

Mean # Visits (se) 1.53 (0.03) 1.34 (0.01) P<0.05

OR (95% CI) Visit 2.52 (2.32 – 2.72) P<0.05

OR (95% CI) Surgery 1.73 (1.29 – 2.26) P<0.05

Cross-Sectional StudyIBD vs. Controls: Hospitalizations

2000-2001

Longobardi CGH 2006

Longitudinal Study II15 Year Follow-up 1987 IBD

Incidence Cohort Between 1987 and 2002

43% IBD cases have an IBD-specific overnight hospitalization

47% CD

21% UC

30% IBD cases have an IBD-specific inpatient visit with a digestive disease surgery (excluding diagnostic endoscopy)

41% CD

16% UCLongobardi CGH 2006

Longitudinal Study II15 Year Follow-up 1987 IBD

Incidence Cohort Readmission Rates Between 1987 and 2002

65% IBD cases admitted for an IBD-specific overnight hospitalization are readmitted

70% CD

53% UC

39% IBD cases admitted for an IBD-specific inpatient visit with a digestive disease surgery (excluding diagnostic endoscopy) are readmitted

39% CD

39% UC

Longitudinal & cross sectional population-based studies in Manitoba

5 year cohort studyThe Manitoba IBD Cohort Study

To describe predictors and patterns of outcomes among subjects diagnosed within 7 years

• Psychological

• Disease outcomes (phenotype)

• Genotype

• Health care utilization

Risk factor study

Population-based case control study

• Crohn’s disease and UC from U of M IBD Research Registry

• Matched healthy controls from MH Registry

• Non-affected sibs

Environmental Study• Assessing water sources to

high and low incidence areas

• Assessing biofilms, filters, and water for microbes

Health Sciences: The Organizational Unit of

ApplicationMolecular &SubmolecularParticles

Cells Organs Individuals Families Communities Societies

Epidemiology

Clinical Research

Pathology, Physiology

Cell Biology

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