Challenges in IBD
Treatment of IBD in the elderly
Jean-Frédéric Colombel, MD
Joannie Ruel, MD
Icahn School of Medicine at Mount Sinai, New York
Conflicts of interest disclosure
J-F Colombel has served as consultant, advisory board member or speaker for or
received research grants from
Abbvie, Amgen, Bristol Meyers Squibb, Celltrion, Ferring, Genentech, Giuliani SPA,
Given Imaging, Janssend and Janssen, Merck & Co., Millenium Pharmaceuticals Inc.,
Nutrition Science Partners Ltd., Pfizer Inc. Prometheus Laboratories, Sanofi,
Schering Plough Corporation, Takeda, Teva Pharmaceuticals, UCB Pharma, Vertex,
Dr. August Wolff GmbH & Co.
Fit versus frail elderly
Outline
• Epidemiology
• Special considerations
• Medical and surgical therapies in the elderly
• Therapeutic strategies in the elderly
Epidemiology
Aging of the population makes elderly-onset IBD and IBD in elderly
patients with disease starting at a younger age a rising problem.
Epidemiology
•
10-15 % of IBD cases will receive their diagnosis > 60 years of
age
o 65% in their sixties
o 25% in their seventies
o 10% in their eighties
•
•
1/20 cases of CD & 1/8 of UC cases are diagnosed in patients
> 60 years of age
Elderly IBD population will increase as majority of IBD
patients attain an older age
Special considerations
Differential diagnosis
•
Consider an appropriate differential diagnosis
before making a definitive diagnosis
•
•
•
•
•
•
•
Ischemic colitis
Infectious colitis
Complicated diverticular disease and SCAD
Drug-associated colitis
Microscopic colitis
Radiation colitis
Neoplasia
Natural history in elderly-onset IBD
EPIMAD
Registry
1988-2006
6 million inhabitants (9.3% of french population)
3 Academic hospitals (CHU) (Lille, Rouen, Amiens)
27 Regional hospitals
250 adult gastroenterologists private and public
12 pediatric gastroenterologists
6 909 CD
367 (5%)
1 175 (17%)
4 310 UC
474 (11%)
689 (10%)
213 (5%)
1 189 (27%)
4 678 (68%)
2 434 (57%)
Gower-Rousseau C et al. Gut 1994
Gower-Rousseau C et al. DLD 2012
UC: disease location and extension according to age
Proctitis
%
70
60
48
41
50
40
Left-sided colitis
50
Extensive colitis
45
31
30
29
20
10
Elderly-onset
0
<17 y
(N=213)
Pediatric-onset
70
%
60
17-39 y
(N=2434)
40-59 y
(N=1189)
%
≥ 60
(N=474)
70
6 years median follow-up
50
34
60
40
50
30
40
30
26
14
Disease extension in 16%
20
Disease extension in 49%
10
49
60
0
At maximal
Follow-up
Charpentier C et al. Gut 2013, Gower-Rousseau C et al. Am J G 2009
17
20
10
0
At maximal
follow-up
CD: Evolution of behavior from diagnosis to maximal
follow-up
Elderly-onset patients (>60 yrs at diagnosis)
5%
17%
Penetrating
Stricturing
10%
22%
78%
Inflammatory
68%
Pediatric-onset patients
(<17 yrs at diagnosis)
Natural history in elderly patients with younger age
at-onset
• In elderly patients with disease
onset at a younger age, a more
aggressive presentation may still
occur.
• Crohn's disease activity does not
burn out with time, and roughly
25% of patients still have active
disease 20 years after diagnosis.
Etienney I et al. GCB 2004
Comorbidities
•
Heart failure
o
•
Caution as worsening and new onset HF have been reported
Diabetes mellitus
o Increased risk of infections
o Steroid use may disturb glycemic control
•
Cancer
o Risk of reactivation of latent cancer
•
Anxiety and depression
o
May influence compliance & outcome of therapy in the elderly
Polypharmacy
• Cross-sectional study of 128 IBD patients aged >65 years, patients were
taking an average of 9.5 routine medications.
• Severe polypharmacy (>10 med) is associated with comorbidity index
scores and steroid use, but not with disease activity or type.
• 80% of patients had at least one medication interaction, with the majority
involving IBD therapies (63%).
• CHECK for interactions before prescribing any IBD therapy in order to prevent
potential adverse effects
Parian AM et al. DDW 2013
Increased risk …
•
•
•
•
Denutrition
Infections including C.difficile colitis
DVT/Thromboembolism
Cancer
o Prior history of malignancy
o Reactivation of latent cancer
Major risk for cancer = past history of
malignancy
Beaugerie L et al. Gut 2013
Increased risk of C.
difficile infection
Increased risk of venous
thromboembolism
3% of elderly UC admissions had
venous thromboembolism
Nguyen GC, Sam J, Am J Gastroenterol 2008; 103: 2272-2280.
Increased risk of hospitalization
•
•
•
•
•
IBD hospitalizations < age 64 (n=105,423)
IBD hospitalizations > age 65 (n=35,573)
Elderly IBD accounted for one quarter of IBD
hospitalizations in 2004
Elderly UC – 33.7% of total UC hospitalizations
Elderly CD – 20.3% of total CD hospitalizations
Ananthakrishnan AN et al. Inflamm Bowel Dis 2009
IBD hospitalization mortality by age
• Significant in-hospital morbidity
and mortality with increased rates
of VTE, pneumonia, UTI, sepsis,
and C.difficile infection.
• Preventive measures:
o VTE/DVT prophylaxis
o Incentive spirometry
o Prompt removal of indwelling
catheters
o Appropriate hand hygiene
o Early initiation of physical and
occupational therapy
Nguyen GC et al. Am J Gastroenterol 2008
Ananthakrishnan AN et al. J Crohns Colitis 2013
Ananthakrishnan AN et al. Gut 2008
Ananthakrishnan AN, et al. Inflamm Bowel Dis 2009
Outline
• Epidemiology
• Special considerations
• Medical and surgical therapies in the elderly
• Therapeutic strategies in the elderly
Specific concerns of medical therapy
•
•
It is currently unknown if treatment goals in older patients
should be different with regard to the need for clinical and
endoscopic remission.
There are no sweeping conclusions to be made from clinical
trials since this aged population with comorbidities is
excluded from almost all new drug development programs.
Specific therapeutic considerations
5-ASAs
•
The wide use of 5-ASAs among patients with elderly- onset CD is
suggestive of a possible role in patients with mild CD.
•
5-ASAs are effective for inducing and maintaining remission in UC
and appear comparable in efficacy in both younger and older
patients.
•
Foam formulation of topical therapy and single daily dosing of oral
5-ASAs may improve compliance.
•
Creatinine clearance should be monitored in the elderly every 6-12
months during therapy, especially when long-term high-dose
regimens are used.
•
Drug interactions with warfarin, 6-MP, AZA
Solberg IC, et al. Clin Gastroenterol Hepatol 2007 Dignass A et al. J Crohns Colitis 2012
Muller AF, et al. Aliment Pharmacol Ther 2005
Specific therapeutic considerations
Corticosteroids
•
The use of corticosteroids carries the risk of precipitating
or exacerbating pre-existing diabetes mellitus, congestive
heart failure, hypertension, altered mental status and
osteoporosis.
•
Early bone densitometry, with repeated annual
examinations, and vit D & calcium supplementation with
> 12 weeks of steroids.
•
Treatment with budesonide may be considered as it
interferes less with bone metabolism; budesonide in UC.
•
Drug interactions: phenytoin, phenobarbital, ephedrine,
rifampin.
Akerkar GA et al. Am J Gastroenterol 1997
Dignass A et al. J Crohns Colitis 2010
Specific therapeutic considerations
Immunomodulators
•
Immunomodulators should be considered in
patients with corticosteroid dependence to
maintain remission.
•
In elderly patients with adequate kidney function,
methotrexate should be considered as aging is a risk
factor for lymphoma and skin cancer in patients
exposed to thiopurines.
•
Allopurinol use could potentially have a benefit in
reducing the thiopurine dose but its concomitant
use with immunomodulators increases the
incidence of infection in older patients with lower
absolute lymphocyte counts.
Dignass A et al. J Crohn’s Colitis 2010
Ansari A et al. Aliment Pharmacol Ther 2010
Govani SM et al. J Crohns Colitis 2010
Magro F et al. J Crohns Colitis 2013
CESAME
Incidence rates of lymphoproliferative disorders according to thiopurine
exposure grouped by age at entry in the cohort
Beaugerie L et al. Lancet 2009
Specific therapeutic considerations
Anti-TNF therapy
DATA ON SAFETY AND EFFICACY
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
Reason for stopping the anti-TNF
EXCLUDING PNR
≥65
(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
Adverse events
≥ 65 anti-TNF
(n=63)
< 65 anti-TNF
(n=118)
≥65 IS-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
-
Lobaton T et al. Leuven group
Why surgery?
•
•
•
More aggressive disease presentation at diagnosis in UC
in the elderly?
Suboptimal response to conventional therapy?
Physicians’ concerns about recommending
immunosuppressive agents for older patients with
comorbidities?
o Disease recurrence tends to be lower postoperatively among
elderly-onset CD
o However, time to recurrence may be shorter for older patients
Wagtmans MJ et al. J Clin Gastroenterol 1998
Surgery
•
•
•
•
Approximately 25% of intestinal IBD surgeries are among
pateints over the age of 55 years.
Older age is associated with an eight-fold increased risk
of in-hospital postoperative mortality, with bowel
perforation and sepsis reported as leading causes of
death.
Older age is associated with an higher postoperative
morbidity
When considering surgical options:
•
•
Consider pre-existing comorbidities – multidisciplinary care
Kaplan GG et al. Arch Surg 2011
Optimization of their nutritional status
Kaplan GG et al. Gastroenterology 2008
Juneja M et al. Dig Dis Sci 2012
IPAA – patient selection
•
For elderly UC patients requiring colectomy : IPAA vs
functional ileostomy:
•
•
Consider their overall functional status
Evaluate the anorectal zone pre-operatively
• Sphincter tone weakens with aging, which may impact
functional outcomes following pouch creation
• >40% of elderly pts experience FI and the majority have
nocturnal seepage
• Major postoperative complications in 24%
• Pouch failure rate : 4%
Delaney CP et al. Ann Surg 2002
Delaney CP et al. Ann Surg 2003
Delaney CP et al. Dis Colon Rectum 2002
Therapeutic strategies in the elderly
Proposed step-up medical therapy in elderlyonset IBD
 Biologic therapy is associated with a risk
of severe infections in elderly patients
with IBD.
Biologic
therapy
Methotrexate*
 A step-up approach of adding therapies
may be preferred over a top-down
approach in elderly-onset IBD.
>
Thiopurines
Antibiotics / Budesonide
 Azathioprine should be avoided in
patients >65 years
 In patients requiring anti-TNF therapy
for induction, monotherapy for
maintenance of remission or association
with methotrexate should be preferred
>
Corticosteroids
5-Aminosalicylates
* In patients with CD
RED FLAGS
•
•
Importance of nutritional status
•
•
•
Vaccination
Chemoprophylaxis for opportunistic
infections
DVT prophylaxis for hospitalized patients
Assess psychologic status & evaluate social support
Conclusion
• There are many uncertainties regarding therapeutic strategies in the
elderly
•
Lack of efficacy and safety data from clinical trials in this population –
often excluded
•
Risks of misdiagnosis
•
Increased risk of side-effects
•
High rate of comorbidities
•
Polypharmacy
• Recent evidence has outlined that the disease course of elderly-onset
IBD is less aggressive than that in the younger population.
• This distinction should be considered when discussing therapeutic
management in this complex population.