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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. Conflicts of interest disclosure. J-F Colombel has served as consultant, advisory board member or speaker for or

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Treatment of IBD in the elderly

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  1. Challenges in IBD Treatment of IBD in the elderly Jean-Frédéric Colombel, MD Joannie Ruel, MD IcahnSchool of Medicineat Mount Sinai, New York

  2. Conflicts of interest disclosure J-F Colombel has served as consultant, advisoryboardmember or speaker for or receivedresearchgrantsfrom 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. PrometheusLaboratories, Sanofi, Schering Plough Corporation, Takeda, Teva Pharmaceuticals, UCB Pharma, Vertex, Dr. August Wolff GmbH & Co.

  3. Fit versus frailelderly

  4. Outline • Epidemiology • Specialconsiderations • Medical and surgicaltherapies in the elderly • Therapeuticstrategies in the elderly

  5. Epidemiology

  6. Aging of the population makeselderly-onset IBD and IBD in elderlypatients withdiseasestartingat a youngeragea risingproblem.

  7. Epidemiology • 10-15 % of IBD cases willreceivetheirdiagnosis > 60 years of age • 65% in their sixties • 25% in their seventies • 10% in theireighties • 1/20 cases of CD & 1/8 of UC cases are diagnosed in patients > 60 yearsof age • Elderly IBD population willincrease as majority of IBD patients attain an olderage

  8. Specialconsiderations

  9. Differentialdiagnosis • Consider an appropriatedifferentialdiagnosisbeforemaking a definitivediagnosis • Ischemiccolitis • Infectiouscolitis • Complicateddiverticulardisease and SCAD • Drug-associatedcolitis • Microscopiccolitis • Radiation colitis • Neoplasia

  10. Natural history in elderly-onset IBD 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 EPIMAD Registry 1988-2006 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. UC: diseaselocation and extension according to age 50 48 41 45 31 29 Elderly-onset Pediatric-onset 49 6 yearsmedianfollow-up 60 34 17 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 behaviorfromdiagnosis 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 withdiseaseonsetat a youngerage, a more aggressivepresentationmaystilloccur. • Crohn'sdiseaseactivitydoes not burn out with time, and roughly 25% of patients still have active disease 20 yearsafterdiagnosis. Etienney I et al. GCB 2004

  14. Comorbidities • Heartfailure • Caution as worseningand new onset HF have been reported • Diabetesmellitus • Increasedrisk of infections • Steroid use maydisturbglycemic control • Cancer • Risk of reactivation of latent cancer • Anxiety and depression • May influence compliance & outcome of therapy in the elderly

  15. Polypharmacy • Cross-sectionalstudy of 128 IBD patients aged >65 years, patients weretaking an average of 9.5 routine medications. • Severepolypharmacy (>10 med) isassociatedwithcomorbidity index scores and steroid use, but not withdiseaseactivity or type. • 80% of patients hadat least one medication interaction, with the majorityinvolving IBD therapies (63%). • CHECK for interactions beforeprescribingany IBD therapy in order to preventpotential adverse effects Parian AM et al. DDW 2013

  16. Increasedrisk … • Denutrition • Infections includingC.difficilecolitis • DVT/Thromboembolism • Cancer • Prior history of malignancy • Reactivation of latent cancer

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

  18. Increasedrisk 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: 2272-2280.

  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-hospitalmorbidity and mortalitywithincreased rates of VTE, pneumonia, UTI, sepsis, and C.difficile infection. • Preventivemeasures: • VTE/DVT prophylaxis • Incentivespirometry • Prompt removal of indwellingcatheters • Appropriate hand hygiene • Early initiation of physical and occupationaltherapy Nguyen GC et al. Am J Gastroenterol 2008 Ananthakrishnan AN et al. J CrohnsColitis 2013 Ananthakrishnan AN et al. Gut 2008 Ananthakrishnan AN, et al. Inflamm Bowel Dis 2009

  22. Outline • Epidemiology • Specialconsiderations • Medical and surgicaltherapies in the elderly • Therapeuticstrategies in the elderly

  23. Specificconcerns of medicaltherapy • It iscurrentlyunknown if treatment goals in older patients shouldbedifferentwith regard to the need for clinical and endoscopicremission. • There are no sweeping conclusions to be made fromclinical trials sincethisaged population withcomorbiditiesisexcludedfromalmost all new drugdevelopment programs.

  24. Specifictherapeuticconsiderations Solberg IC, et al. Clin GastroenterolHepatol 2007 Dignass A et al. J CrohnsColitis 2012 Muller AF, et al. Aliment PharmacolTher 2005

  25. Specifictherapeuticconsiderations Akerkar GA et al. Am J Gastroenterol 1997 Dignass A et al. J CrohnsColitis 2010

  26. Specifictherapeuticconsiderations Dignass A et al. J Crohn’sColitis 2010 Ansari A et al. Aliment PharmacolTher 2010 Govani SM et al. J CrohnsColitis 2010 Magro F et al. J CrohnsColitis 2013

  27. CESAME Incidence rates of lymphoproliferativedisordersaccording to thiopurineexposuregrouped by ageat entry in the cohort Beaugerie L et al. Lancet 2009

  28. Specifictherapeuticconsiderations

  29. Older age is an independent risk factor for serious infections and mortality in IBD patients on anti-TNFs Cottone M et al. ClinGastroenterolHepatol 2011

  30. Efficacy of Anti-TNF in theelderly ALL PATIENTS EXCLUDING PNR P < 0.001 Lobaton T et al. Leuven group.

  31. Safety of anti-TNF in the elderly1 Lobaton T et al. Leuven group

  32. Whysurgery? • More aggressivediseasepresentationatdiagnosis in UC in the elderly? • Suboptimalresponse to conventionaltherapy? • Physicians’ concerns about recommending immunosuppressive agents for older patients withcomorbidities? • Diseaserecurrence tends to belowerpostoperativelyamongelderly-onset CD • However, time to recurrencemaybeshorter for older patients Wagtmans MJ et al. J Clin Gastroenterol 1998

  33. Surgery • Approximately 25% of intestinal IBD surgeries are amongpateints over the age of 55 years. • Olderageisassociatedwith an eight-foldincreasedrisk of in-hospitalpostoperativemortality, withbowel perforation and sepsisreported as leading causes of death. • Olderageisassociatedwith an higherpostoperativemorbidity • Whenconsideringsurgical options: • Considerpre-existingcomorbidities – multidisciplinary care • Optimization of theirnutritionalstatus Kaplan GG et al. ArchSurg 2011 Kaplan GG et al. Gastroenterology 2008 Juneja M et al. Dig Dis Sci 2012

  34. IPAA – patient selection • For elderly UC patients requiringcolectomy : IPAA vs functionalileostomy: • Considertheiroverallfunctionalstatus • Evaluate the anorectal zone pre-operatively • Sphincter toneweakenswithaging, whichmay impact functionaloutcomesfollowingpouchcreation • >40% of elderly pts experience FI and the majority have nocturnal seepage • Major postoperative complications in 24% • Pouchfailure 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. Therapeuticstrategies in the elderly

  36. Proposedstep-up medicaltherapy in elderly-onset IBD • Biologictherapyisassociatedwith a risk of severe infections in elderly patients with IBD. • A step-up approach of addingtherapiesmaybepreferred over a top-down approach in elderly-onset IBD. • Azathioprineshouldbeavoided in patients >65 years • In patients requiring anti-TNF therapy for induction, monotherapy for maintenance of remission or association withmethotrexateshouldbepreferred * In patients with CD

  37. RED FLAGS • Importance of nutritional status • Chemoprophylaxis for opportunistic infections • Vaccination • DVT prophylaxisfor hospitalized patients • Assesspsychologicstatus & evaluatesocial support

  38. Conclusion • There are manyuncertaintiesregardingtherapeuticstrategies in the elderly • Lack of efficacy and safety data fromclinical trials in this population – oftenexcluded • Risks of misdiagnosis • Increasedrisk of side-effects • High rate of comorbidities • Polypharmacy • Recentevidence has outlinedthat the disease course of elderly-onset IBD islessaggressivethanthat in the younger population. • This distinction shouldbeconsideredwhendiscussingtherapeutic management in thiscomplex population.

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