1. Treatment of IBD in the elderly
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

2. 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.

3. Fit versus frail elderly

4. Outline Epidemiology Special considerations
Medical and surgical therapies in the elderly
Therapeutic strategies in the elderly

5. Epidemiology

6. Aging of the population makes elderly-onset IBD and IBD in elderly patients with disease starting at a younger age a rising problem.

7. Epidemiology
10-15 % of IBD cases will receive their diagnosis > 60 years of age
65% in their sixties
25% in their seventies
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

8. Special considerations

9. 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

10. Natural history in elderly-onset IBD
EPIMAD Registry
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
4 310 UC
367 (5%)
474 (11%)
689 (10%)
1 175 (17%)
213 (5%)
1 189 (27%)
2 434 (57%)
4 678 (68%)
Gower-Rousseau C et al. Gut 1994
Gower-Rousseau C et al. DLD 2012

11. 6 years median follow-up
UC: disease location and extension according to age 50 48 41 45 31 29
Elderly-onset 17 49 34
Pediatric-onset
6 years median follow-up 60 26
Disease extension in 16% 14
Disease extension in 49%
At maximal
Follow-up
Charpentier C et al. Gut 2013, Gower-Rousseau C et al. Am J G 2009

12. CD: Evolution of behavior from diagnosis to maximal follow-up
Elderly-onset patients (>60 yrs at diagnosis) 5%
Penetrating
10%
17%
Stricturing
22%
78%
Inflammatory
68%
Pediatric-onset patients (<17 yrs at diagnosis)

13. 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

14. Comorbidities Heart failure Diabetes mellitus Cancer
Caution as worsening and new onset HF have been reported
Diabetes mellitus
Increased risk of infections
Steroid use may disturb glycemic control
Cancer
Risk of reactivation of latent cancer
Anxiety and depression
May influence compliance & outcome of therapy in the elderly

15. 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

16. Increased risk … Denutrition Infections including C.difficile colitis
DVT/Thromboembolism
Cancer
Prior history of malignancy
Reactivation of latent cancer

17. Major risk for cancer = past history of malignancy
Beaugerie L et al. Gut 2013

18. Increased risk of C. difficile infection

19. Increased risk of venous thromboembolism
3% of elderly UC admissions had
venous thromboembolism
Nguyen GC, Sam J, Am J Gastroenterol 2008; 103:

20. 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

21. 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:
VTE/DVT prophylaxis
Incentive spirometry
Prompt removal of indwelling catheters
Appropriate hand hygiene
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

22. Outline Epidemiology Special considerations
Medical and surgical therapies in the elderly
Therapeutic strategies in the elderly

23. 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.

24. 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 Dignass A et al. J Crohns Colitis 2012
Muller AF, et al. Aliment Pharmacol Ther 2005

25. 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

26. 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

27. CESAME
Incidence rates of lymphoproliferative disorders according to thiopurine exposure grouped by age at entry in the cohort
Beaugerie L et al. Lancet 2009

28. Specific therapeutic considerations
Anti-TNF therapy
DATA ON SAFETY AND EFFICACY

29. Older age is an independent risk factor for
serious infections and mortality in IBD patients
on anti-TNFs
Patients >65 years with biologics
(n=95)
Patients <65 years with biologics
(n=190)
Patients >65 years without biologics
Serious
infections
11%
2.6%
0.5%
Neoplasms 3% 0% 2%
Deaths
10% 1%
Cottone M et al. Clin Gastroenterol Hepatol 2011

30. Efficacy of Anti-TNF in the elderly
ALL PATIENTS
EXCLUDING PNR
Reason for stopping the anti-TNF
≥65
(n=63)
<65 (n=118)
Primary NR (%) 44 19
Loss of response (%) 6 37
Side effects (%) 29
Remission-other (%) 31 14
P < 0.001
Lobaton T et al. Leuven group.

31. 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 (%)
(p= 0.026) 3 16
Any SAE (%)
(p= 0.028) 39 10
Need for surgery (%) 19 14
Death (%) 6 1
Malignancy (%) 2
Acute reaction with antiTNF (%) 5 11 -
Delayed hypersensitivity with antiTNF (%) 4
Lobaton T et al. Leuven group

32. 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?
Disease recurrence tends to be lower postoperatively among elderly-onset CD
However, time to recurrence may be shorter for older patients
Wagtmans MJ et al. J Clin Gastroenterol 1998

33. 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
Optimization of their nutritional status
Kaplan GG et al. Arch Surg 2011
Kaplan GG et al. Gastroenterology 2008
Juneja M et al. Dig Dis Sci 2012

34. 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

35. Therapeutic strategies in the elderly

36. Proposed step-up medical therapy in elderly-onset IBD
Biologic therapy is associated with a 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.
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
Biologic
therapy
Methotrexate*
>
Thiopurines
Antibiotics / Budesonide
Corticosteroids
5-Aminosalicylates
* In patients with CD

37. RED FLAGS Importance of nutritional status
Chemoprophylaxis for opportunistic infections
Vaccination
DVT prophylaxis for hospitalized patients
Assess psychologic status & evaluate social support

38. 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.