In a meta-analysis by Ananthakrishnan et al.,²⁸ left sided UC disease was the most common (45%; 95% CI, 40%-52%), followed by pancolitis (31%), and proctitis (22%). Subsequent studies have shown similar trends, with left sided UC being the most common (range, 34%-56%), followed by pancolitis (range, 14%-38%), and proctitis (range, 13%-45%).^{8,11,13,14,15,16}

Data regarding proximal extension in these patients is contradictory. In a study from South Korea, proximal extension was less common (22.9%) elderly-onset UC than in the younger-onset UC (32.0%),¹³ whereas in a French population-based cohort study, 84% of patients with elderly-onset UC remained stable with no proximal extension.¹⁷

In a recent meta-analysis, the most common disease location for elderly-onset CD was colonic (44%; 95% CI, 36%-52%), followed by ileal (32%), and ileo-colonic disease (26%).²⁸ Upper gastrointestinal involvement was uncommon (7%). Inflammatory disease was the most common behavior (68%; 95% CI, 61%-74%), followed by stricturing (24%), and penetrating disease (8%). Perianal involvement was relatively uncommon (12%). In subsequent studies, colonic location was most common (range, 30%-65%) followed by ileal (range, 10%-50%), and ileo-colonic (range, 10%-38%), with inflammatory behavior being most common (68%-96%), followed by stricturing and penetrating disease.^{8,9,11,12,24,25}

Elderly-onset UC appears to follow an indolent disease course. In a recent meta-analysis, overall rates of surgery, immunomodulator use, and biologic use in patients with UC were 9%, 17%, and 4%, respectively.²⁸ Patients with elderly-onset UC were less likely to receive immunomodulators (OR, 0.60; 95% CI, 0.45-0.79) or biologic therapies (OR, 0.41; 95% CI, 0.27-0.62)27 and were more likely to undergo surgery (OR, 1.36; 95% CI, 1.18-1.57; P<0.001).²⁸ Higher rates of surgery indicate that the disease course is probably not as mild or reflect a preference for surgery in patients because of fear of adverse events with immunosuppressants. Similarly, in the EPIMAD registry,¹⁷ the lower proportion of patients with extensive colitis at diagnosis, but the higher rate of early colectomy and no difference in the use of medications, suggests a similar disease course. In a recent study from South Korea, the proportion of patients with extensive colitis (54.4%) requiring systemic steroid (53.5%) and immunosuppressants (26.6%) was significantly higher among elderly-onset UC.¹³ Similar findings were also reported by a recent study from Hong Kong.¹⁶

In the meta-analysis by Ananthakrishnan et al.,²⁸ overall rates of surgery, immunomodulator use, and biologic use in elderly-onset CD patients were 32%, 32%, and 15%, respectively. Patients with elderly-onset disease were significantly less likely to receive immunomodulators or biologics than patients with younger-onset disease, but the need for surgery was similar for both types of patients with no differences at the 1- and 5-year follow-up. The rates of disease progression in patients with elderly-onset CD have been lower than those in patients with non-elderly-onset CD, as suggested in a recent Dutch study⁸ and in the EPIMAD registry where the disease behavior remained stable in 91% of elderly patients after a median follow-up period of 6 years.¹⁷ Elderly-onset CD patients are at a higher risk of surgery at diagnosis, although the long-term rate of surgery remains similar between elderly-onset and young-onset CD patients. Unlike UC, disease course, progression, hospitalization, and surgery in elderly-onset CD has remained consistent over the years.

Another recent study found that pure colonic location (L2) was more frequent among patients aged >70 years at diagnosis than among patients aged >60 years at diagnosis (73% vs. 57%), with inflammatory behavior being most common.²⁹ There was no significant difference in either group with respect to treatment with aminosalicylates (5-ASAs), oral corticosteroids, and anti-TNF therapies. Risk of surgery was similar in both groups. The lower risk of disease extension or severity in elderly-onset CD patients treated with 5-ASAs has led to the provocative, but plausible, suggestion that colonic CD of elderly onset may have a UC phenotype or even that 5-ASAs may have a possible role in this subgroup of patients.^17,29,30

Elderly patients with IBD appear to have a higher risk of hospitalization. Ananthakrishnan and Binion³¹ reported that 25% of all IBD-related hospital admissions in the USA were in patients aged over 65 years. These patients were likely to be more malnourished, anemic and hypovolemic with higher transfusion requirements, and with longer postoperative hospital stays especially after surgery.

Venous thromboembolic complications are more common in patients with elderly-onset IBD and stem from inflammatory disease activity and associated hypercoagulability, reduced physical activity, and the potential for dehydration.²

5-ASAs are foundational therapy for the induction and maintenance of remission in UC.^2,33 Despite their controversial role in CD, they are commonly prescribed in elderly patients with CD. In the EPIMAD study, 5-ASAs were prescribed in 75% of patients with similar clinical phenotype in CD and UC.¹⁷ Amongst the CD patients, 68% received 5-ASAs at 1 year, 77% at 5 years, and 80% at 10 years of follow-up. Over 50% of the UC patients were on 5-ASA monotherapy and did not require surgery.¹⁷ Between 88% and 90% of patients with colonic CD were receiving 5-ASAs with over two-thirds given maintenance therapy at maximal follow-up.¹⁷ The widespread use of 5-ASAs in patients with CD is in agreement with other population-based cohorts.¹⁹ This has led to a provocative suggestion that 5-ASAs may in fact have a role in elderly-onset CD.³⁰

The combination of oral and topical 5-ASAs is more effective than oral therapy alone.³³ Complex dosing regimens and polypharmacy could negatively influence compliance and once-daily dosing regimens may be preferable.³³ Anorectal dysfunction in the elderly ranges between 10% to 25% in hospitalized patients and 4% in outpatients.³⁴ This raises the issue of difficulties with the use of topical therapy arising from physical limitations with reduced retention of enema fluid in the presence of active inflammation. Reduction in the volume of the enema or substitution with a corticosteroid foam preparation may circumvent this problem.³⁵

Although 5-ASAs are relatively safe, there have been rare reports of nephrotoxicity and interstitial nephritis, which appear idiosyncratic rather than age-related.³⁶ Common side effects include nausea, vomiting, abdominal pain, headache, and rash.³³ Paradoxical worsening of colitis can occur in less than 5% of patients, which improves after discontinuing the drug.³⁷

The potential for drug interaction with other agents such as warfarin, increasing its anticoagulant activity,³⁸ increased 6-thioguanine levels with potential for myelosuppression,³⁹ and interaction with isoniazid should also be considered.³⁶

Corticosteroids are the cornerstone of decisive induction of remission in UC patients with an inadequate response to 5-ASAs, in acute severe UC, and to induce clinical remission in CD.^33,40

They are associated with a higher risk of adverse events. In a Canadian study of 3,522 patients with elderly-onset IBD, the rate of serious infections (pneumonia, intestinal infections, C. difficile enterocolitis) was significantly higher in patients with IBD exposed to steroid use within the previous 6 months with the risk being highest in current steroid users (adjusted OR, 2.3; 95% CI, 1.8-2.9).⁴¹ The Therapy, Resource, Evaluation, and Assessment Tool registry also reported a hazard ratio (HR) of 1.6 (95% CI, 1.2-2.1) for serious infections associated with steroid use within 6 months and higher mortality related to corticosteroid exposure.⁴² Dose-related side effects have been reported in 40% of elderly patients with long-term corticosteroid use and osteoporosis in 16% of patients.⁴³ Despite the sheer futility of prolonged steroid exposure with its inherent risks, elderly persons with IBD appear to be treated with corticosteroid therapy. Furthermore, the published literature to date demonstrates inadequacies in exit strategies once steroids are initiated. In a study of 393 elderly patients with IBD (>65 years), corticosteroid usage had doubled from 35% (1991-2000) to 64% (2001-2010).⁴⁴ Disappointingly, elderly-onset patients with IBD also received higher average prednisolone doses than younger patients (8 mg/day vs. 2.2 mg/day respectively, P<0.005) and over a third of elderly-onset IBD patients received steroids for over 6 months.⁴⁴ A U.S. Medicare cohort study of over 8,500 patients with elderly-onset IBD found that 20% of patients receiving anti-TNF therapy had received corticosteroids for over 3 months, and 10% for over 6 months.⁴⁵ Additionally, 43% of elderly patients had received anti-TNF concomitantly with corticosteroids in multiple courses spanning over 3 months.⁴⁵ It is likely that physician hesitancy in escalating to immunomodulatory therapy, even in “well-selected” patients, and the notion that corticosteroid therapy is “safer” may be driving this practice. These studies emphasize the importance of steroid stewardship with careful contingency planning.

Corticosteroids are associated with other serious morbidities such as altered mental state and depression, fluid retention, glaucoma, osteoporosis and fractures.⁴⁶ In one study, osteoporotic-related fractures and osteonecrosis were noted in 15% of patients with elderly IBD.⁴⁷ The widespread prevalence of malabsorption and calcium and vitamin D deficiency in the elderly should prompt early and regular bone densitometry assessments. Bisphosphonates should be considered alongside vitamin D and calcium supplementation.^33,40

Steroids may reduce the activity of drugs such as phenytoin, phenobarbital, ephedrine, and rifampicin. Anticoagulant efficacy of warfarin may also be affected, and careful monitoring of coagulation parameters is recommended.²

Budesonide may be recommended for induction of remission in mild-to-moderate distal small bowel and right-sided colonic CD.⁴⁰ A novel formulation of budesonide in a multimatrix release formulation has recently been approved for use in mild-moderate extensive UC. The judicious use of these formulations as a bridge to conventional steroids may reduce unnecessary steroid exposure although the full impact of this intervention needs further and formal study.

Immunomodulators may be indicated in elderly patients demonstrating corticosteroid dependence.^2,40 A network meta-analysis of nearly 40 randomized controlled trials in CD patients found that neither thiopurines nor methotrexate improved the odds of achieving remission over placebo but a significant difference was noted with respect to maintenance of remission.⁴⁸ The relative paucity of clinical data on the use of thiopurines in elderly patients is reflected in the disparate practices with respect to their use.⁴⁹

In a retrospective study of 393 patients with IBD aged over 65 years, one-third were on long-term corticosteroids (over 6 months) with only 6% on thiopurines and 1% on methotrexate.⁴⁴ While it is plausible that differential prescribing patterns for immunomodulatory therapy may be driven by physician hesitancy, immunomodulators are associated with a higher risk of opportunistic infections and other serious adverse effects such as a higher risk of malignancy, as discussed below.^{50,51,52,53,54} Taken together, the data suggest sufficient cause for concern with the use of thiopurines in elderly persons and when possible suitable alternatives should be preferred.² Although methotrexate has not been studied specifically in elderly patients, no adverse reports have emerged from their use in elderly persons with rheumatoid arthritis and psoriasis and they have not been associated with malignancy. Methotrexate has been used in CD but consensus opinion currently does not favor its use as monotherapy in UC.^2,33,40 The role of methotrexate in elderly patients with IBD needs to be studied further.

The role of anti-TNF therapy in the decisive induction and maintenance of remission in moderate to severely active IBD has been established through pivotal trials for nearly 2 decades.^2,33,40 Data supporting their efficacy in elderly patients are limited and conflicting, with some studies showing similar results in elderly- and younger-onset IBD^55,56 and others suggesting lower efficacy.^57,58 A U.S. study found the rates of partial/complete response in the elderly to be significantly lower than in younger patients with IBD (61% vs. 83%).⁵⁷ In a nested case control study from Leuven in which 239 patients were treated with anti-TNF, the clinical response at 10 weeks was significantly lower in elderly-onset IBD than in younger-onset IBD patients (68% vs. 89%), although the long-term efficacy (>6 months) was similar between the 2 groups (79% vs. 83%).⁵⁵ In another study of 95 patients with elderly-onset IBD treated with anti-TNF between 2000 and 2009, 65% of patients with CD and 59% with UC achieved clinical remission as opposed to 59% and 57% in a control group of under 65 years.⁵⁶ Discontinuation rates in elderly patients at 12 months have also been higher, with concomitant use of thiopurines being the only significant predictor of early discontinuation, potentially driven by infection risk from bimodal immunosuppression.⁵⁷

Data on safety of anti-TNF therapy consistently report increased rates of adverse events in elderly patients. Early experience from the Mayo Clinic demonstrated that 3 of 4 deaths from infliximab therapy occurred in elderly patients, although the independent contribution of age was unclear in these patients who have a longer disease course, and more severe disease and multiple comorbidities.⁵⁸ In another long-term cohort study of 734 patients with IBD treated with infliximab, age was the only predictor of mortality in patients on anti-TNF therapy.⁵⁹ In a multicenter retrospective case-control study, the rate of infections (11.5% vs. 2.6% vs. 0.5%, P<0.001) and mortality (10.5% vs. 1.1% vs. 2.1%, P<0.001) was higher in elderly patients (>65 years) on anti-TNF than in younger patients (<65 years) on anti-TNF vs. elderly patients not on anti-TNF.⁵⁶ The Massachusetts study also reported a higher risk of adverse events in elderly anti-TNF users, which led to 70% of elderly patients discontinuing therapy after 2 years.⁵⁷ In the study from Leuven, elderly patients on anti-TNF therapy had a higher risk of any adverse event, and on multivariate analysis, age ≥65 was the only risk factor for a serious adverse event on anti-TNF.⁵⁵

Anti-integrins are a novel addition to the expanding therapeutic armamentarium for IBD. In the post hoc analysis in GEMINI trials, the efficacy and safety profiles of vedolizumab were similar across all age groups (<35, 35 to <55, and ≥55 years).⁶⁰ Vedolizumab-treated patients aged ≥55 had the lowest incidence of serious infections (0.9 per 100 person-years) and adverse events leading to hospitalization (14.8 per 100 person-years). There were no differences in hematological events, malignancy, or deaths with regard to age. In a recent study of 29 elderly IBD patients (10 UC, 19 CD), the efficacy (48% clinical response at 14 weeks, 55% at 52 weeks), and safety (13.8% adverse events) of vedolizumab were similar to the results of GEMINI trials.⁶¹ Head-to-head comparisons between vedolizumab and other biological agents discussed above are now needed to position it within the current treatment algorithms of active IBD. The gut specificity and safety profile of vedolizumab may be appealing especially where monotherapy is desirable.²

Total colectomy with permanent ileostomy (TPCI) is the most commonly performed procedure in elderly-onset UC (77.3%), whereas total colectomy with ileal pouch-anal anastomosis (IPAA) is the preferred procedure in younger patients, which may be largely attributable to concerns about the disturbance of sphincter function and fecal incontinence after surgery in elderly patients (79.9%).^2,13,67

A systemic review by Shung et al.⁶⁸ reported surgery-associated complications observed in elderly IBD patients. Postoperative complications after surgery decreased from the years 1960-1984 to 1994-1999 and elderly age was not a predictor of adverse outcome.⁶⁹ There was no significant difference in morbidity or 30-day mortality between TPCI versus IPAA procedures.⁷⁰ The incidence of postoperative cardiac and pulmonary complications was higher in the elderly than in younger patients.⁶⁶ Functional outcomes after IPAA are generally similar to those of younger patients.⁶⁸ In a recent study, which used the American College of Surgeons National Surgical Quality Improvement Program dataset,⁷¹ the odds of 30-day postoperative mortality in elderly patients was 4.4-fold greater in UC (6.1% vs. 0.7%) and 11.7-fold greater in CD (4.2% vs. 0.3%) than those in younger patients with IBD. The rates of postoperative complications (34.5% vs. 21.3%, P<0.001) including cardiac dysfunction (2.5% vs. 0.3%, P<0.001), renal dysfunction (2.7% vs. 0.9%, P<0.001), neurologic complications (0.8% vs. 0.2%, P<0.001), ventilator dependence (7.2% vs. 1.3%, P<0.001), and infection (21% vs. 14.7%, P<0.001) were significantly higher in the elderly patients than in younger patients. In a study of 32,833 patients with UC, elective colectomy was associated with better survival than medical therapy (HR, 0.70; 95% CI, 0.54-0.90), and on subgroup analysis, this effect remained significant only in the age group >50 years (HR, 0.60; 95% CI, 0.45-0.79).⁷²

IPAA is the surgical procedure of choice in UC if the patient has good anal sphincter function with no history of fecal incontinence.^22,33,73 Pouch function deteriorates with increasing age with fecal incontinence, an effect that may be more pronounced in the elderly.^2,74 Despite this, patients report a high level of satisfaction with IPAA, with 89% of elderly UC patients stating that they would opt to undergo the procedure again and 96% willing to recommend it to others.⁷⁵

Taken together, these observations emphasize the importance of careful patient selection, assessment of local motor, cognitive, and anal sphincter function in planning and timing optimal surgical procedures for best possible outcomes.