Incidence and prevalence of IBD in elderly patients is rising worldwide.
Considering the frailty of this population, clinical management of older people affected by IBD necessitates the balancing risk of disease with treatment-related complications.
This prospective-retrospective observational study (parallel cohort study) compared elderly- and adult-onset IBD, evaluating clinical features at the moment of diagnosis, natural history, IBD-related hospitalizations, therapeutic strategies, and complications related to the disease or to therapy during a mean follow up period of 21 years.
Our findings lead us to make some recommendations that may assist the clinical management of IBD in the elderly.
Regarding risk factors for the development of IBD, we did not find any difference in terms of family history of IBD. It has been suggested that genetic factors may influence the development of early-onset IBD, but such studies encompassed a pediatric or young control group 17,19, while this control group was composed of adult patients, with IBD onset between 40 and 64 years.
Therefore, we observed no difference in term of genetic predisposition or risk factors. As shown in other studies 4, clinical features of elderly-onset IBD are generally similar to those of adult patients, although some differences may arise 2.
There was no difference for symptoms that lead to a diagnosis of IBD, except for abdominal pain, which was more common amongst adults, both for UC and CD, respectively. This unreported abdominal pain in the elderly might be due to decreased intestinal motility or better ability to tolerate pain 21,17.
The clinical course for elderly-onset IBD was evaluated considering time to first relapse post disease onset, number of relapses, number of IBD-related hospitalizations, need for surgery and mean time to surgery post follow-up.
Time to first relapse was similar regardless of the initial therapy used to induce remission. Moreover, frequency of disease flares did not differ either, which might suggest that disease behavior was similar in both cohorts, both for CD and UC. Although elderly-onset -IBD course is often thought to be milder in severity 22,5,23 results are controversial with some population-based studies suggesting that elderly-onset -IBD may have a course similar to adult-onset IBD 6,7, as this study found.
Other studies evaluating the clinical course of IBD in the elderly have yielded conflicting results. Some suggest that the natural history of elderly-onset IBD is less aggressive than for younger patients 17,8, 24, 19,25, while others found a similar clinical course 26,10. This heterogeneity could be, in part, due to a lack of uniformity surrounding the age defining elderly-onset IBD and the age of the control group in different studies 27. In the present study, like other authors 28, we defined elderly-onset IBD as after the age of 65, which is the conventional threshold defining geriatric age, but several other ages have been used in other studies, for example over 50 years 19, over60 years 3,8,29 and over 70 years 30.
In accordance with previous studies 3,8,5 we found that, for CD, the need for surgery did not differ between EO-CD and AO-CD, while time to surgery was significantly shorter for elderly patients.
Due to biological therapy use being significatively more frequent in adults, it is possible that the lack of usage of these drugs in the elderly could give rise to an earlier necessity for surgery. On the other hand, it might imply a longer asymptomatic phase of the disease, which gives rise to surgery earlier following diagnosis. Similarly to other authors 8,10,31, we did not find any differences in terms of surgery for UC. Time to surgery did not differ in UC for either cohort, which might support a recommendation not to delay surgery in the elderly. In fact, it has been shown that in the elderly UC complications and mortality are higher when surgery is delayed 32.
Despite a similar clinical course and number of relapses, EO-IBD were more likely to be hospitalized due to IBD relapse. As geriatric patients tend to have functional impairment and increased numbers of comorbidities, they might need hospitalization more frequently, due to their frailty, independent of the severity of the relapse. In our study, comorbidities were significatively more frequent amongst elderly (CIRS), which might explain the higher number of IBD-related hospitalizations. This finding is consistent with what has previously been described by Nguyen et al., regarding the annual cost of IBDrelated hospitalizations, which are significatively higher in EO-IBD than AO-IBD 12.
The therapeutic strategy for the induction of remission at the time of diagnosis was similar for both groups, while maintenance therapy was different with biological/anti-TNFα used almost exclusively in adult patients. This result is consistent with previous studies 26,13; and might reflect physician concern with adverse effects and the risk of infection in the elderly 14,1,15,16. Compared to younger patients, elderly patients have immunodeficiency, higher cancer risk, detrimental polypharmacy and altered drug metabolism. This might raise concerns for clinicians regarding the use of immunosuppressing agents, biological therapies and standard dose therapy 33.
A study suggested that elderly patients hospitalized with IBD were less likely to receive immunomodulators and/or biological agents during hospitalization or before admission compared with younger IBD patients. 34
Indeed, little is known about the safety of biological agents in elderly IBD patients, as most trials exclude IBD patients over 60 years. Some studies have reported that ageing is a risk factor for serious infections in IBD patients receiving biological drugs 35,36,37,38. We found that, in the subgroup of IBD patients with no biological therapy, infections were significantly more frequent among elderly-onset IBD than adult-onset IBD.
Old age itself is related to an increased risk of serious infection among patients with IBD 39,40.
Moreover, biological therapy is related to an increased risk of infection in the elderly, compared to older or younger patients not receiving such therapies 38. Therefore, the infection risk in this population needs to be taken into account when biological therapy is prescribed in elderly-onset IBD, and all the precautions to minimize risks, such as appropriate vaccination, need to be implemented.
Biological therapy has been also associated with risk of malignancy 41,38, and older age is an independent risk factor for the development of cancer. Thus, concerns have been raised surrounding biological therapy for older patients, in particular those with a history of cancer.
However, newer and more selective biological therapies have been approved recently. Due to its gut-selective anti-inflammatory action, vedolizumab is considered to be safe both for the risk of cancer onset/recurrence and for non-intestinal infections 42,43, 44.
Real-life studies for ustekinumab also show promising results in this age group 45.
Overall, the results of our study suggest that elderly-onset IBD could have a clinical presentation and a natural history similar to adult-onset IBD. There are some peculiarities in the clinical presentation and natural history of the disease, but, all in all, natural history of elderly-onset IBD does not appear to be less aggressive than adult-onset IBD. On the other hand, patients’ characteristics are different: elderly patients are more likely to present comorbidities and poly-pharmacotherapy, they are more prone to medical complications and have increased susceptibility to infections and steroid-related side-effects 46. All these factors have to be considered when treating elderly-onset IBD. In particular, the management of elderly-onset IBD requires the evaluation of the disease burden, balancing safety and efficacy of treatment. Further studies encompassing elderly-onset IBD subjects are needed to understand the natural history of the disease, while randomized controlled trials, including elderly IBD patients, are required to achieve the best management of IBD in this growing segment of the population.