Inflammatory Bowel Disease in the Elderly Steven N. Fine, MD Chief of GI, MetroWest Med Cntr Med...

Inflammatory Bowel Disease in the Elderly

Inflammatory Bowel Disease in the Elderly

Steven N. Fine, MD

Chief of GI, MetroWest Med Cntr

Med Director, Boston Endo Cntr

Steven N. Fine, MD

Chief of GI, MetroWest Med Cntr

Med Director, Boston Endo Cntr

IBD and agingIBD 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?

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 agingIBD and aging

Is there a difference between developing IBD at an advanced age versus having IBD at a young age and growing older?

Is there a difference between developing IBD at an advanced age versus having IBD at a young age and growing older?

Take Home Point #1Take Home Point #1

The onset of IBD at an advance age occurs more frequently than previously thought.

The onset of IBD at an advance age occurs more frequently than previously thought.

EpidemiologyEpidemiology

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

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




EpidemiologyEpidemiology

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




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





The burden on the health care system from older IBD patients is rising.

The burden on the health care system from older IBD patients is rising.

Epidemiology:National Hospital Discharge

Survey

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

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’sUS Hospitalization: Crohn’s

US Hospitalizations: UCUS Hospitalizations: UC


IBD at an advanced age has a less aggressive natural history and a different distribution at presentation.


Natural HistoryNatural 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 elderly-

onset IBD reported to date.

Charpentier C. Gut 2014; 63:423-432.

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 elderly-

onset IBD reported to date.

Charpentier C. Gut 2014; 63:423-432.

IBD and age: Northern France Study

IBD and age: Northern France Study

IBD and age: distribution at presentation

IBD and age: distribution at presentation

IBD and age: Natural HistoryIBD 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

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


Long-Term Course of Crohn’s Disease

Long-Term Course of Crohn’s Disease

Cosnes J et al. Inflammatory Bowel Disease. 2002;8:244–250.These data precede biologic therapy for Crohn’s disease

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StricturingInflammatory

N = 2002 patients with Crohn’s disease since diagnosis of the disease

Probability of remaining FREE of complications

Clinical CourseClinical Course

Northern France StudyNorthern 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.”


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.”


CD diagnosed at a young age:Natural History

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

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 ageIBD 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; 27:129-33Harper PC. Arch Int Med 1986; 146: 753-5

Softley A. Scand J Gastroenterol 1988; 23:27-30Triantafillidis JK. Digest Liver Dis 2000; 32:498-503Polito JM. Gastroenterology 1996; 111:580-6

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; 27:129-33Harper PC. Arch Int Med 1986; 146: 753-5

Softley A. Scand J Gastroenterol 1988; 23:27-30Triantafillidis JK. Digest Liver Dis 2000; 32:498-503Polito JM. Gastroenterology 1996; 111:580-6

IBD at advanced ageIBD 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)

Colonic involvement is more likely Overall less risk for surgery Less risk for progression Less fistulizing disease


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

Prospective study 20 geographic areas in 12 European

countries 2201 IBD patients 10 year clinical follow up




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


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




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

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


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.

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 ConditionsComorbid 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%

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%

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%

PolypharmacyPolypharmacy

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

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 CourseClinical Course


Look for, prophylax for, and treat C.difficile and venous thromboembolism.

Look for, prophylax for, and treat C.difficile and venous thromboembolism.

Risk Factors for Osteoporosis in IBD

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

Medications Advanced age Low body mass Reduced physical activity Family History of Osteoporosis TOB

Ali T. Am J Med 2009; 122: 599-604

AGA Recommendationsfor Managing Osteoporosis

AGA Recommendationsfor Managing Osteoporosis

IBD patient:Any of:-Prolonged steroid use(>3mo consec or recurrent courses)-Low trauma, fragility fracture-Postmenopausal or male age >50-Hypogonadism

DXA

T score >-1

Basic Prevention:-Ca/Vit D-exercise-smoking cessation-avoid alcohol-minimize corticosteroids-treat hypogonadismT score -2.5 to -1

Prevention and:-repeat DXA 2 years-Prolonged CS consider BP and DXA 1 year

T score <-2.5

Vert FractureRegardless of DXA

Prevention and:-Screen other causes low BMD-Bisphosphonate therapy or-Refer to bone specialist

Gastroenterology 2003;124:795-841

Adherence to GuidelinesAdherence to Guidelines

Survey 1000 AGA members 304 responders; 258 appropriate 49% utilized guidelines

Wagnon J. Inflam Bowel Dis 2009; 15: 1082-1089

Survey 1000 AGA members 304 responders; 258 appropriate 49% utilized guidelines

Wagnon J. Inflam Bowel Dis 2009; 15: 1082-1089

Reasons for Non-UtilizationReasons for Non-Utilization


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.

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.


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.

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.


IBD patients over age 50 should have Bone Density Testing and then follow-up depending on results (follow the guidelines)

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

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, post-

operative mortality increasesGreenwald DA. Curr Treat Options in Gastro 2003; 6:213-225Almony G. Scand J Gastroenterol 2002; 37:1025-28Juneja M. Dig Dis Sci 2012; 57:2408-15Guy TS. Surg Clin North Am 2001; 81:159-168Kaplan GG. Arch Surg 2011; 146: 959-964

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, post-

operative mortality increasesGreenwald DA. Curr Treat Options in Gastro 2003; 6:213-225Almony G. Scand J Gastroenterol 2002; 37:1025-28Juneja M. Dig Dis Sci 2012; 57:2408-15Guy TS. Surg Clin North Am 2001; 81:159-168Kaplan GG. Arch Surg 2011; 146: 959-964

IBD in the Elderly: Surgical Outcomes

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

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

Mayo Clinic 2002 pts IPAA for UC or FAP Over a 9 year period Question: does age affect surgical

outcome?




No increase in pouch failure in the elderly Increase in incontinence No difference in quality of life


No increase in pouch failure in the elderly Increase in incontinence No difference in quality of life



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.

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 ElderlyFit 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

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.



IBD and the Elderly:5-ASA

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


Gisbert JP. Inflamm Bowel Dis 2007; 13:629-38

Katz S. Gastroenterol & Hep 2008; 4:337-47

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


Gisbert JP. Inflamm Bowel Dis 2007; 13:629-38


IBD and the ElderlyAntibiotics

IBD and the ElderlyAntibiotics

Neuropathic effects of metronidazole Effects on warfarin Cdifficile

Greenwald DA. Curr Treat Option Gastroenterol 2003; 6:213-25



Neuropathic effects of metronidazole Effects on warfarin Cdifficile

Greenwald DA. Curr Treat Option Gastroenterol 2003; 6:213-25



IBD and the Elderly:Steroids

IBD and the Elderly:Steroids

Infection Osteoporosis Mental status Depression HTN DM


Infection Osteoporosis Mental status Depression HTN DM


Hypertension Hypokalemia Hyperglycemia Osteonecrosis CHF Consider budesonide

Hypertension Hypokalemia Hyperglycemia Osteonecrosis CHF Consider budesonide

IBD and the Elderly:Methotrexate

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 osteoporosisKatz 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

Decrease in GFR impacts on drug clearance Effects on warfarin May increase atherosclerosis and

cardiovascular mortality by increasing levels of homocysteine

Increase risk of osteoporosisKatz 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

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 CaPresent DH. Ann Int Med 1989; 111:641-9 Connell WR. Gut 1993; 34:1981-5

O’Brien JJ. Gastroenterology 1991; 101:39-46

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 CaPresent DH. Ann Int Med 1989; 111:641-9 Connell WR. Gut 1993; 34:1981-5

O’Brien JJ. Gastroenterology 1991; 101:39-46


6MP/AZA pose a significant risk of lymphoproliferative disorders in the elderly, so methotrexate may be a better option.

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

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



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

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



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

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


Anti-TNFs have a lower efficacy and a higher risk in the elderly

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 elderly IBD patients.

Step-Up Therapy is the better approach than Top-Down Therapy for elderly IBD patients.

Medical TherapyMedical Therapy

Additional Thoughts/ConcernsAdditional Thoughts/Concerns

Colon Cancer Screening/Surveillance Depression Compliance Intestinal Bacteria Vaccination


Long MD. J Crohns Colitis 2013; 1-7

Enck P. Z Gastroenterol. 2009; 47: 653-8

Colon Cancer Screening/Surveillance Depression Compliance Intestinal Bacteria Vaccination


Long MD. J Crohns Colitis 2013; 1-7

Enck P. Z Gastroenterol. 2009; 47: 653-8

Conclusions: Take Home PointsConclusions: 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.


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.



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.

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.


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.

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.

Inflammatory Bowel Disease in the Elderly Steven N. Fine, MD Chief of GI, MetroWest Med Cntr Med...

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