6Aging of the population makes elderly-onset IBD and IBD in elderly patients with disease starting at a younger age a rising problem.
7Epidemiology10-15 % of IBD cases will receive their diagnosis > 60 years of age65% in their sixties25% in their seventies10% in their eighties1/20 cases of CD & 1/8 of UC cases are diagnosed in patients > 60 years of ageElderly IBD population will increase as majority of IBD patients attain an older age
9Differential diagnosis Consider an appropriate differential diagnosis before making a definitive diagnosisIschemic colitisInfectious colitisComplicated diverticular disease and SCADDrug-associated colitisMicroscopic colitisRadiation colitisNeoplasia
10Natural history in elderly-onset IBD EPIMAD Registry6 million inhabitants (9.3% of french population)3 Academic hospitals (CHU) (Lille, Rouen, Amiens)27 Regional hospitals250 adult gastroenterologists private and public12 pediatric gastroenterologists6 909 CD4 310 UC367 (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 1994Gower-Rousseau C et al. DLD 2012
116 years median follow-up UC: disease location and extension according to age504841453129Elderly-onset174934Pediatric-onset6 years median follow-up6026Disease extension in 16%14Disease extension in 49%At maximalFollow-upCharpentier C et al. Gut 2013, Gower-Rousseau C et al. Am J G 2009
12CD: Evolution of behavior from diagnosis to maximal follow-up Elderly-onset patients (>60 yrs at diagnosis)5%Penetrating10%17%Stricturing22%78%Inflammatory68%Pediatric-onset patients (<17 yrs at diagnosis)
13Natural 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
14Comorbidities Heart failure Diabetes mellitus Cancer Caution as worsening and new onset HF have been reportedDiabetes mellitusIncreased risk of infectionsSteroid use may disturb glycemic controlCancerRisk of reactivation of latent cancerAnxiety and depressionMay influence compliance & outcome of therapy in the elderly
15PolypharmacyCross-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 effectsParian AM et al. DDW 2013
16Increased risk … Denutrition Infections including C.difficile colitis DVT/ThromboembolismCancerPrior history of malignancyReactivation of latent cancer
17Major risk for cancer = past history of malignancy Beaugerie L et al. Gut 2013
19Increased risk of venous thromboembolism 3% of elderly UC admissions hadvenous thromboembolismNguyen GC, Sam J, Am J Gastroenterol 2008; 103:
20Increased 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 2004Elderly UC – 33.7% of total UC hospitalizationsElderly CD – 20.3% of total CD hospitalizationsAnanthakrishnan AN et al. Inflamm Bowel Dis 2009
21IBD 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 prophylaxisIncentive spirometryPrompt removal of indwelling cathetersAppropriate hand hygieneEarly initiation of physical and occupational therapyNguyen GC et al. Am J Gastroenterol 2008Ananthakrishnan AN et al. J Crohns Colitis 2013Ananthakrishnan AN et al. Gut 2008Ananthakrishnan AN, et al. Inflamm Bowel Dis 2009
22Outline Epidemiology Special considerations Medical and surgical therapies in the elderlyTherapeutic strategies in the elderly
23Specific 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.
24Specific therapeutic considerations 5-ASAsThe 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, AZASolberg IC, et al. Clin Gastroenterol Hepatol Dignass A et al. J Crohns Colitis 2012Muller AF, et al. Aliment Pharmacol Ther 2005
25Specific therapeutic considerations CorticosteroidsThe 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 1997Dignass A et al. J Crohns Colitis 2010
26Specific therapeutic considerations ImmunomodulatorsImmunomodulators 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 2010Ansari A et al. Aliment Pharmacol Ther 2010Govani SM et al. J Crohns Colitis 2010Magro F et al. J Crohns Colitis 2013
27CESAMEIncidence rates of lymphoproliferative disorders according to thiopurine exposure grouped by age at entry in the cohortBeaugerie L et al. Lancet 2009
28Specific therapeutic considerations Anti-TNF therapyDATA ON SAFETY AND EFFICACY
29Older age is an independent risk factor for serious infections and mortality in IBD patientson anti-TNFsPatients >65 years with biologics(n=95)Patients <65 years with biologics(n=190)Patients >65 years without biologicsSeriousinfections11%2.6%0.5%Neoplasms3%0%2%Deaths10%1%Cottone M et al. Clin Gastroenterol Hepatol 2011
30Efficacy of Anti-TNF in the elderly ALL PATIENTSEXCLUDING PNRReason for stopping the anti-TNF≥65(n=63)<65 (n=118)Primary NR (%)4419Loss of response (%)637Side effects (%)29Remission-other (%)3114P < 0.001Lobaton T et al. Leuven group.
31Safety of anti-TNF in the elderly1 Adverse events≥ 65 anti-TNF(n=63)< 65 anti-TNF (n=118)≥65 IS-CS(n=70)Infection (%)211220Infection with hospitalization (%)(p= 0.026)316Any SAE (%)(p= 0.028)3910Need for surgery (%)1914Death (%)61Malignancy (%)2Acute reaction with antiTNF (%)511-Delayed hypersensitivity with antiTNF (%)4Lobaton T et al. Leuven group
32Why 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 CDHowever, time to recurrence may be shorter for older patientsWagtmans MJ et al. J Clin Gastroenterol 1998
33SurgeryApproximately 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 morbidityWhen considering surgical options:Consider pre-existing comorbidities – multidisciplinary careOptimization of their nutritional statusKaplan GG et al. Arch Surg 2011Kaplan GG et al. Gastroenterology 2008Juneja M et al. Dig Dis Sci 2012
34IPAA – patient selection For elderly UC patients requiring colectomy : IPAA vs functional ileostomy:Consider their overall functional statusEvaluate the anorectal zone pre-operativelySphincter tone weakens with aging, which may impact functional outcomes following pouch creation>40% of elderly pts experience FI and the majority have nocturnal seepageMajor postoperative complications in 24%Pouch failure rate : 4%Delaney CP et al. Ann Surg 2002Delaney CP et al. Ann Surg 2003Delaney CP et al. Dis Colon Rectum 2002
36Proposed 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 yearsIn patients requiring anti-TNF therapy for induction, monotherapy for maintenance of remission or association with methotrexate should be preferredBiologictherapyMethotrexate*>ThiopurinesAntibiotics / BudesonideCorticosteroids5-Aminosalicylates* In patients with CD
37RED FLAGS Importance of nutritional status Chemoprophylaxis for opportunistic infectionsVaccinationDVT prophylaxis for hospitalized patientsAssess psychologic status & evaluate social support
38ConclusionThere are many uncertainties regarding therapeutic strategies in the elderlyLack of efficacy and safety data from clinical trials in this population – often excludedRisks of misdiagnosisIncreased risk of side-effectsHigh rate of comorbiditiesPolypharmacyRecent 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.