Transcript Fine_IBD and age

Inflammatory Bowel Disease
in the Elderly
Steven N. Fine, MD
Chief of GI, MetroWest Med Cntr
Med Director, Boston Endo Cntr
IBD and aging




Are there differences between older and
younger patients with IBD?
What are the differences?
What are the similarities?
How do we alter our approach to
treatment?
IBD and aging

Is there a difference between developing
IBD at an advanced age versus having
IBD at a young age and growing older?
Take Home Point #1

The onset of IBD at an advance age
occurs more frequently than previously
thought.
Epidemiology



Incidence varies from 3.1-14.6 cases per
100,000 for CD and 2.2-14.3 for UC
Incidence of CD after age 60 is 3.5-4.0 per
100,000
Incidence of UC after age 60 is 4.5-8.0 per
100,000
Loftus EV. Gastroenterol Clin N Am 2002; 31:1-20
Robertson DJ. Gastroenterol Clin N Am 2001; 30:409-26
Evans PE. Aging Health 2007; 3:77-84
Epidemiology



The onset of CD occurs after age 60 in
16% of patients (range: 7-26%)
The onset of UC occurs after age 60 in
12% of patients (range: 8-20%)
65% in 60s, 25% in 70s, 10% in 80s
Loftus EV. Gastroenterol Clin N Am 2002; 31:1-20
Robertson DJ. Gastroenterol Clin N Am 2001; 30:409-26
Evans PE. Aging Health 2007; 3:77-84
Take Home Point #2

The burden on the health care system
from older IBD patients is rising.
Epidemiology:
National Hospital Discharge
Survey



Using data from NHDS
Age-specific rates of hospitalization over
consecutive 5-year periods
Found more pronounced increase in rates
of hospitalization for older age group (65+)
Sonnenberg A. J Clin Gastroenterol 2009; 43:297-300
US Hospitalization: Crohn’s
700
600
500
65+
45-64
-44
400
300
200
100
0
1970- 1975- 1980- 1985- 1990- 1995- 2000- 20054
9
4
9
4
9
4
6
US Hospitalizations: UC
600
500
400
65+
45-64
-44
300
200
100
0
1970-4 1975-9 1980-4 1985-9 1990-4 1995-9 2000-4
Take Home Point #3

IBD at an advanced age has a less
aggressive natural history and a different
distribution at presentation.
Natural History





Northern France, EPIMAD Registry
1988-2006; 6 million people; 9.3% of pop
3 Academic and 27 Regional Hospitals
262 Gastroenterologists
Largest population-based study of elderlyonset IBD reported to date.
Charpentier C. Gut 2014; 63:423-432.
IBD and age: Northern France
Study
IBD and age: distribution at
presentation
IBD and age: Natural History


For Crohn’s: disease extension in 31% for
<17 years vs 8% for >60 years
For Ulcerative Colitis: disease extension in
49% for <17 years vs 16% for >60 years
Charpentier C. Gut 2014; 63:423-432
Long-Term Course of Crohn’s
Disease
Probability of remaining FREE of complications
N = 2002 patients with Crohn’s disease since diagnosis of the disease
100
Cumulative Probability (%)
90
80
70
60
Penetrating
50
40
30
Inflammatory
Stricturing
20
10
0
0
12
24
36
48
60 72
84 96
108 120 132 144 156 168 180 192 204 216 228 240
Months
These data precede biologic therapy for Crohn’s disease
Cosnes J et al. Inflammatory Bowel Disease. 2002;8:244–250.
CD: Evolution of behavior from diagnosis to maximal follow-up
Proportions of behaviors according to disease duration
Clinical Course
Elderly-onset patients (>60 yrs at diagnosis)
5%
17%
Penetrating
Stricturing
10%
22%
78%
Inflammatory
68%
Pediatric-onset patients
(<17 yrs at diagnosis)
Northern France Study
Conclusion: “Clinical course is mild in
elderly-onset IBD patients. This information
would need to be taken into account by
physicians when therapeutic strategies are
established.”
Charpentier C. Gut 2014; 63:423-432
CD diagnosed at a young age:
Natural History





No difference in activity 3 years after dx
compared with 20 years after dx
24% of Crohn’s patients had active
disease 20 years later
48% in remission on treatment
28% in remission off treatment
Crohn’s Disease does not “burn out”
Etienney I. Gastroenterol Clin Biol 2004; 28: 1233-9
IBD at advanced age





Relapses less likely
Fewer post-surgical recurrence
1st episode of UC more fulminant and more
likely to require surgery
Acute abdomen more common in CD
Lower frequency of FHx of IBD
Wagtmans MJ. J Clin Gastroenterol 1998; 27:129-33
Harper PC. Arch Int Med 1986; 146: 753-5
Softley A. Scand J Gastroenterol 1988; 23:27-30
Triantafillidis JK. Digest Liver Dis 2000; 32:498-503
Polito JM. Gastroenterology 1996; 111:580-6
IBD at advanced age




Colonic involvement is more likely
Overall less risk for surgery
Less risk for progression
Less fistulizing disease
Gisbert JP. Aliment Pharmacol Ther 2014; 1-19
Ha C. Curr Gastroenterol Rep 2013; 15: 310 (1-9)
IBD and the Elderly:
Mortality




Prospective study
20 geographic areas in 12 European
countries
2201 IBD patients
10 year clinical follow up
Wolters FL. Gut 2006; 55:510-8
IBD and the Elderly:
Mortality



Increased mortality risk in patients with Crohn’s
Disease
10 years after diagnosis
Above 40 years at diagnosis was the sole factor
associated with increased mortality
Wolters FL. Gut 2006; 55:510-8
IBD and the Elderly:
Mortality



Age is an independent predictor of
mortality in IBD inpatients
Malnutrition, male sex, need for surgery
were factors associated with higher risk
In IBD, elderly age predictive of mortality
with an odds ratio of 3.91
Ananthakrishnan A. Dig Dis 2009; 27: 327-34
Ananthakrishnan A. Inflamm Bowel Dis 2009; 15: 182-9
Take Home Point #4

Comorbidities and polypharmacy affect
outcome, morbitity and mortality.
Katz S. Inflamm Bowel Dis 2013; 19: 225772.
Ha C. Curr Gastroenterol Rep 2013; 15: 310 (1-9).
Kaplan GG. Arch Surg 2011; 146: 959-964.
Comorbid Conditions







CAD 33.8%
CLD 22.6%
CHF 22.6%
PVD 7.4%
CVD 12.5%
PUD/GIB 17.8%
Mod-sev Liver 10.7%







DM 18.8%
DM and end-org 9.4%
CVA 12.5%
Mod to sev RD 11.5%
Rheum 10.2 %
Dementia 2.5%
HIV 0.5%
Polypharmacy




128 IBD pts greater than 65 yo
Average of 9.5 routine medications
>10 meds (severe polypharmacy)
associated with comorbidity scores and
steroid use
80% of pts had at least one medication
interaction, 63% involved IBD therapy.
Parian AM. DDW 2013: Su1130
!" #$%&' %( )$*' +), -)! "#
$%
&&%
' %
() #*" -%#.*, " )
Clinical Course
Take Home Point #5

Look for, prophylax for, and treat C.difficile
and venous thromboembolism.
Risk Factors for Osteoporosis in
IBD






Medications
Advanced age
Low body mass
Reduced physical activity
Family History of Osteoporosis
TOB
Ali T. Am J Med 2009; 122: 599-604
AGA Recommendations
for Managing Osteoporosis
T score >-1
IBD patient:
Any of:
-Prolonged steroid use
(>3mo consec or recurrent
courses)
-Low trauma, fragility fracture
-Postmenopausal or male age
>50
-Hypogonadism
T score -2.5 to -1
DXA
T score <-2.5
Vert Fracture
Regardless of DXA
Gastroenterology 2003;124:795-841
Basic Prevention:
-Ca/Vit D
-exercise
-smoking cessation
-avoid alcohol
-minimize
corticosteroids
-treat hypogonadism
Prevention and:
-repeat DXA 2 years
-Prolonged CS consider BP
and DXA 1 year
Prevention and:
-Screen other causes low BMD
-Bisphosphonate therapy or
-Refer to bone specialist
Adherence to Guidelines




Survey
1000 AGA members
304 responders; 258 appropriate
49% utilized guidelines
Wagnon J. Inflam Bowel Dis 2009; 15: 1082-1089
Reasons for Non-Utilization
Adherence to Guidelines




Retrospective study
George Washington University
26.5% had DEXA
13.7% had vitamin D testing


Less than half ordered by GI MDs
35.7% had vitamin D deficiency
Bakshi A. Am J Gastroenterol 2009; 104: 791.
Adherence to Guidelines





Retrospective
George Washington University
Men with IBD
9% had vitamin D testing
21.5% had DEXA

65% had either osteoporosis or osteopenia
Nguyen HD. Am J Meds Health 2010; 4: 71-4.
Take Home Point #6

IBD patients over age 50 should have
Bone Density Testing and then follow-up
depending on results (follow the
guidelines)
IBD and the Elderly:
Surgery




Rate of early surgery for fulminant disease for
UC higher in elderly; after 5 years for young
Surgery for CD in elderly with higher mortality
rate and complications
8-fold increase in post-op mortality (perf/sepsis)
As the number of comorbidities increase, postoperative mortality increases
Greenwald DA. Curr Treat Options in Gastro 2003; 6:213-225
Almony G. Scand J Gastroenterol 2002; 37:1025-28
Juneja M. Dig Dis Sci 2012; 57:2408-15
Guy TS. Surg Clin North Am 2001; 81:159-168
Kaplan GG. Arch Surg 2011; 146: 959-964
IBD in the Elderly: Surgical
Outcomes





Medical College of Wisconsin
IBD surgeries in patients after 65 yo
Compared with 3 control groups: 18-35 yo,
36-49 yo, 50-64 yo
No difference in complication rate.
Comorbidity Index and nutritional status
are risk factors.
Bautista MC. Dig Dis Sci 2013; 58:2955-62
IBD and the Elderly:
Ileal Pouch-Anal Anastomosis





Mayo Clinic
2002 pts
IPAA for UC or FAP
Over a 9 year period
Question: does age affect surgical
outcome?
Chapman JR. Arch Surg 2005; 140:534-40
IBD and the Elderly:
Ileal Pouch-Anal Anastomosis



No increase in pouch failure in the elderly
Increase in incontinence
No difference in quality of life
Chapman JR. Arch Surg 2005; 140:534-40
Take Home Point #7

There is less tendency for surgery in the
elderly, but worse outcomes; and
comorbid conditions and nutritional status
are risk factors for poor surgical outcomes.
Fit Elderly and Frail Elderly




concept for individualizing therapy
walker, wheelchair, falls, polypharmacy,
comorbidities, oxygen, cognitive function,
level of activity help to define risk.
guide therapeutic decisions.
no scientific studies.
Katz S. Inflamm Bowel Dis 2013; 19: 2257-72
Katz S. Gastroenterol & Hep 2008; 4: 337-47
IBD and the Elderly:
5-ASA




More attention may be needed for patients
with chronic renal insufficiency and 5-ASA
Exacerbations of the IBD may increase
risk due to dehydration and pre-renal state
Half-life is increased in elderly
Interactions with warfarin and 6MP/AZA
Katz S. Inflamm Bowel Dis 2013; 19: 2257-72
Gisbert JP. Inflamm Bowel Dis 2007; 13:629-38
Katz S. Gastroenterol & Hep 2008; 4:337-47
IBD and the Elderly
Antibiotics



Neuropathic effects of metronidazole
Effects on warfarin
Cdifficile
Greenwald DA. Curr Treat Option Gastroenterol 2003; 6:213-25
Katz S. Gastroenterol & Hep 2008; 4:337-47
Katz S. Inflamm Bowel Dis 2013; 19: 2257-72
IBD and the Elderly:
Steroids






Infection
Osteoporosis
Mental status
Depression
HTN
DM
Katz S. Gastroenterol & Hep 2008; 4:
337-47






Hypertension
Hypokalemia
Hyperglycemia
Osteonecrosis
CHF
Consider budesonide
IBD and the Elderly:
Methotrexate




Decrease in GFR impacts on drug
clearance
Effects on warfarin
May increase atherosclerosis and
cardiovascular mortality by increasing
levels of homocysteine
Increase risk of osteoporosis
Katz S. Inflamm Bowel Dis 2013; 19: 2257-72
Landewe RBM. Lancet 2000; 355:1616-7
Greenwald DA. Curr Treat Options Gastro 2003; 6:213-225
IBD and the Elderly:
6MP/Azathioprine




Myelosuppression is unrelated to age
Significant dose reduction if used with
allopurinol; inhibit warfarin effect
Use TPMT enzyme activity and Thiopurine
metabolites to guide therapy
MTX to avoid risk of Lymphoma/Skin Ca
Present DH. Ann Int Med 1989; 111:641-9
Connell WR. Gut 1993; 34:1981-5
O’Brien JJ. Gastroenterology 1991; 101:39-46
CESAME
Incidence rates of lymphoproliferative disorders according to thiopurine
exposure grouped by age at entry in the cohort
Beaugerie L et al. Lancet 2009
Take Home Point #8

6MP/AZA pose a significant risk of
lymphoproliferative disorders in the
elderly, so methotrexate may be a better
option.
IBD and the Elderly:
Anti-TNFs




Evaluated the safety of infliximab in older
pts (70 yo)
Used infliximab withdrawal and the reason
for withdrawal as outcome
9 hospitals around Burgundy, France
83 pts (RA and AS)
Chevillotte-Maillard H. Rheumatology 2005; 44:696-7
IBD and the Elderly:
Anti-TNFs
14
12
10
8
20-40
41-60
60+
6
4
2
0
% infections
IBD and the Elderly:
Anti-TNFs




Northern Ireland
94 patients
Severe inflammatory arthritis
Mean age of pts with major infections was
65 yo
Cairns AP. The Ulster Medical Journal 2002; 71: 101-5
IBD and the Elderly:
Anti-TNFs




Mayo Clinic experience
500 patients; Crohn’s Disease
1% mortality
3 of the 5 attributable deaths were
associated with “relatively old age” and
“severe comorbidities”
Colombel J. Gastroenterlogy 2004;126:19-31
Older age is an independent risk factor for
serious infections and mortality in IBD patients
on anti-TNFs
Patients >65 Patients <65
years with
years with
biologics
biologics
(n=95)
(n=190)
Patients >65
years
without
biologics
(n=190)
Serious
infections
11%
2.6%
0.5%
Neoplasms
3%
0%
2%
Deaths
10%
1%
2%
Cottone M et al. Clin Gastroenterol Hepatol 2011
Efficacy of Anti-TNF in the elderly
ALL PATIENTS
EXCLUDING PNR
Reason for stopping the anti-TNF
(n=63)
<65
(n=118)
Primary NR (%)
44
19
Loss of response (%)
6
37
Side effects (%)
19
29
Remission-other (%)
31
14
P < 0.001
Lobaton T et al. Leuven group.
Safety of anti-TNF in the elderly1
(n=63)
< 65 anti-TNF
(n=118)
-CS
(n=70)
Infection (%)
21
12
20
Infection with hospitalization (%)
13
(p= 0.026)
3
16
Any SAE (%)
56
(p= 0.028)
39
10
Need for surgery (%)
19
10
14
Death (%)
6
1
Malignancy (%)
6
2
19
Acute reaction with antiTNF (%)
5
11
-
Delayed hypersensitivity with antiTNF (%)
4
11
-
Adverse events
-TNF
Lobaton T et al. Leuven group
Take Home Point #9

Anti-TNFs have a lower efficacy and a
higher risk in the elderly
Take Home Point #10

Step-Up Therapy is the better approach
than Top-Down Therapy for elderly IBD
patients.
Medical
Therapy
Proposed step-up medical therapy in
elderly-onset IBD
Biologic therapy use increases the risk of
severe infections in elderly patients with
IBD.
A step-up approach of adding therapies
may be preferred over a top-down
approach in elderly-onset IBD.
In patients requiring anti-TNF therapy for
induction, monotherapy for
maintenance of remission should be the
preferred choice given the greater risk of
lymphoma and infection in this age
group with combination therapy.
If a patient has failed
immunomodulators, monotherapy with
anti-TNF therapy would appear
appropriate.
Biologic
therapy
Methotrexate*
>
Thiopurines
Antibiotics / Budesonide
>
Corticosteroids
5-Aminosalicylates
* In patients with CD
Additional Thoughts/Concerns





Colon Cancer Screening/Surveillance
Depression
Compliance
Intestinal Bacteria
Vaccination
Gisbert JP. Aliment Pharmacol Ther 2014; 1-19
Long MD. J Crohns Colitis 2013; 1-7
Enck P. Z Gastroenterol. 2009; 47: 653-8
Vaccination concerns
Stop
IS / TNF inhibitor
Diagnosis of IBD
3 weeks
Live and live
attenuated
vaccines
3 months*
NO
VZV/MMR (children)
Others: case by case
Inactivated
vaccines
DTP / influenza / pneumococcal polysaccharide / recombinant hepatitis B /
HPV
* This delay may be reduced to 1 month in case of use of corticosteroids alone
IS = immunosuppressant; DTP = diphtheria/tetanus toxoids and pertussis vaccine; HPV = human
papillomavirus vaccine; MMR = measles, mumps and rubella vaccine; VZV = varicella-zoster virus vaccine.
Conclusions: Take Home Points



The onset of IBD at an advanced age
occurs more frequently than previously
thought.
The burden on the healthcare system from
older IBD patients is rising.
IBD at an advanced age has a less
aggressive natural history and a different
distribution at presentation.
Conclusions: Take Home Points




Comorbidities and polypharmacy affect
outcomes, morbidity, and mortality.
Look for, prophylax for, and treat Cdifficile
and venous thromboembolism.
IBD patients over age 50 should have
bone density testing.
Less tendency for surg, but worse
outcomes; comorbid conditions&nutritional
status are RFs for poor surgical outcomes.
Conclusions: Take Home Points



6MP/AZA pose significant risk of
lymphoproliferative disorders in the
elderly, so methotrexate may be a better
option.
Anti-TNFs have a lower efficacy and a
higher risk in the elderly.
Step-Up Therapy is the better approach
than Top-Down Therapy for the elderly.