Elderly-onset inflammatory bowel disease in Asia: clinical characteristics and therapeutic strategies
Article information
Abstract
The incidence and prevalence of elderly-onset inflammatory bowel disease (EO-IBD) are increasing worldwide. The rising incidence of EO-IBD in Asia is driven by rapid industrialization and an aging population. Older patients often have multiple comorbidities and polypharmacy, which make diagnosis and management of the disease more challenging. Additionally, Asian patients with EO-IBD exhibit unique clinical characteristics, including frequent ileal involvement. Differences in phenotype between patients with EO-IBD in Western and Asian countries may explain subsequent disparities in the natural history of these patients. Although EO-IBD often manifests with a mild clinical course at diagnosis, it poses distinct diagnostic and therapeutic challenges. Understanding these characteristics is essential for optimizing patient care and for optimizing patient outcomes. In this review, we explore the epidemiology, disease burden, and clinical characteristics of EO-IBD in Asia, as well as the therapeutic approaches for treating the disease.
INTRODUCTION
Inflammatory bowel disease (IBD) is a chronic, progressive, and idiopathic inflammatory disorder of the gastrointestinal tract that requires lifelong treatment [1]. The incidence of IBD, including Crohn’s disease (CD) and ulcerative colitis (UC), has been increasing worldwide, including in Asia [2-8]. The sharp increase in the incidence of IBD in Asia is considered to be largely due to environmental changes, including industrialization, westernized diets, and the resulting changes in the microbiota [9-12]. Although, IBD is most often diagnosed in young adults, its diagnosis has been increasing in the older population. Older patients with IBD can be categorized into 2 groups: those newly diagnosed with IBD at an advanced age, and those diagnosed at a younger age who continue to experience the chronic effects of IBD. The aging population has emerged as a worldwide concern driven by advances in diagnosis and treatment. Notably, Asian countries, including Korea and Japan, are experiencing an increase in super-elderly populations. Elderly-onset IBD (EO-IBD) or older-onset IBD is characterized as IBD that is newly diagnosed in patients aged 60 years or older, although some studies, including the Japanese nationwide registry, have used ≥65 years [13-15]. Current estimates suggest that approximately 10% to 15% of the IBD population is classified as EO-IBD [13,16,17]. These numbers are expected to continue increasing with the aging population.
Although data are lacking, the incidence and prevalence of EO-IBD in Asian countries are projected to increase in tandem with the aging population. Consequently, EO-IBD has emerged as an important clinical condition in this region [15,18-23]. The diagnosis of EO-IBD poses a significant challenge, necessitating differential diagnosis from numerous other diseases. Furthermore, patients with EO-IBD may manifest clinical symptoms and respond differently to treatment compared with those with younger-onset IBD. A notable distinction has been observed in the demographic and phenotypic characteristics of Asian patients when compared with those from Western countries [7,24,25].
Therefore, we aimed to examine the epidemiology, clinical characteristics, diagnostic challenges, and therapeutic considerations of Asian patients with EO-IBD because understanding the unique characteristics of this distinct disease population will be crucial for clinicians in this region.
EPIDEMIOLOGY OF EO-IBD IN ASIA
Traditionally, IBD peaks in early adulthood; however, a second peak of onset has been increasingly recognized in the older population. The incidence of EO-IBD varies among Western countries. The Danish National Patient Registry (1995–2012) reported that 21.0% of patients with UC and 17.0% of patients with CD were diagnosed after 60 years of age [26]. However, in a French population-based cohort (1988–2006), only 9.0% of patients were diagnosed with EO-IBD (11.0% with UC and 5.0% with CD) [27]. Similar results were reported in Olmstead County, Minnesota, with 12.0% diagnosed with UC and 6.0% with CD [28,29]. Overall, the incidence of EO-UC is higher than that of EO-CD. This phenomenon corresponds with data indicating that the age of onset for patients with UC exhibits a second peak after 60 years of age [30]. A study that analyzed the burden of IBD using data from the Global Burden of Disease Study 2021 [31] demonstrated that the overall incidence rate remained stable from 2000 to 2021. However, the incidence of EO-IBD has increased, accounting for 11.0% of total cases in 2021 [17]. The proportion of EO-IBD cases is highest in the Americas (14.4%) and in countries with a high sociodemographic index (14.5%), whereas it is only 5.7% in countries with a low sociodemographic index.
The prevalence of EO-IBD has also been reported in Asia (Table 1) [8,15,18-22,32-36]. However, the rate was significantly lower than that observed in Western countries. In the Korean prospective CONNECT study, conducted between January 2009 and September 2019, 1,175 patients were diagnosed with CD [37]. Of these, only 26 (2.2%) were classified as having EO-CD [18]. A large hospital-based study in Korea reported that 29 of 2,989 patients with CD had EO-CD (1.0%) [19]. Conversely, EO-UC has a much higher incidence in Korea. The frequency of EO-UC markedly increased from 3.9% (1977–1999) to 9.7% (2008–2014) (P<0.001) [32]. Additionally, a Songpa-Kangdong population-based cohort study (1986–2015) identified 99 patients with EO-UC (10.3%) [22].
Epidemiology and Disease Burden of EO-IBD in Asia
The Japanese nationwide IBD registry revealed that 9.9% of patients were diagnosed with EO-UC (aged ≥65 years) between 2004 and 2009 [15]. Another Japanese study reported that the ratio of patients with EO-UC (aged ≥60 years) increased from 1.6% of those diagnosed before 2000 to 13.9% of those diagnosed after 2001 [33].
Data from China highlight regional heterogeneity. A retrospective, single-center study from China (2014–2021) demonstrated that 23.4% (184/787) of the patients diagnosed with IBD were >60 years of age [34]. However, it is uncertain whether these patients met the diagnostic criteria for EO-IBD or were older patients with IBD at a younger age.
Another Chinese cohort study (1998–2020) revealed that among 1,609 individuals diagnosed with IBD, 8.0% (n=129) were classified as having EO-IBD, with 99 cases of UC and 30 of CD [36]. Of this patient population, 17.1% had a long-term history of smoking (>35 years) [35].
A cross-sectional retrospective analysis at 2 centers in India revealed that 4.7% of the patients had EO-IBD; of these, 69.4% had UC and 30.6% had CD [21]. A retrospective population-based study from Taiwan (2016–2020), including 2,595 newly registered patients with IBD, determined that 22.9% of the patients with UC (392/1,715) and 18.9% of those with CD (167/880) were diagnosed with EO-IBD [8]. The authors suggested that with the aging population, the healthcare system may have difficulty managing EO-IBD in patients with age-related comorbidities [8].
The Asia-Pacific Crohn’s and Colitis Epidemiology Study (including 9 countries from the Asia-Pacific region) reported that the incidences of EO-UC and EO-CD were approximately 0.8/100,000 and 0.3/100,000 population, respectively [38].
The number of patients with EO-UC in Hong Kong increased from 0.1/100,000 in 1991 to 1.3/100,000 in 2010 [36]. The proportion of newly diagnosed patients with EO-UC has shown a marked and statistically significant increase over the past two decades, from 3.0% before 1990 to 21.6% after 2010. In addition, a recent study reported that 270 (11.2%) patients in the Hong Kong IBD registry (1981–2016) had EO-IBD. Compared with adult-onset IBD, patients with EO-IBD had a higher UC-to-CD ratio (3.82:1 vs. 1.39:1) [20].
In summary, the incidence of EO-IBD in Asia has trended upward, although this trend varies across different countries and remains lower than that in Western countries. EO-UC is more prevalent than EO-CD in Asia as well as in Western countries.
Several studies have indicated that a greater proportion of Asian patients with EO-IBD are current or former smokers [20,32,33,35]. In a French cohort study, EO-IBD patients had a lower family history (3.0%) than non-EO-IBD patients (7.0%) [27]. Similarly, Asian EO-IBD patients are less likely to have a family history of (1.9%–4.0%) [20,32]. These findings suggest that patients with EO-IBD are influenced more by environmental factors than genetic factors.
DISEASE BURDEN OF EO-IBD IN ASIA
EO-IBD is consistently associated with an increased risk of complications. The risk of malignancy is a major concern in patients with EO-IBD. Previous studies in Taiwan and Hong Kong demonstrated that the risk of non-colorectal malignancies was substantially increased in Asian patients with IBD [39,40]. A large Chinese cohort also reported a nearly 3-fold higher overall cancer incidence in EO-IBD than in adult-onset disease, with colorectal, urinary tract, and hematologic malignancies being the most frequent (26.9 vs. 9.5 per 1,000 person-years, respectively; relative risk [RR], 2.83), patients with EO-IBD also had a shorter interval from IBD diagnosis to cancer development and higher tumor-related mortality than those with adult-onset IBD [35]. In contrast, findings from Western populations generally indicate that the overall cancer risk in older patients with IBD does not significantly differ from that of the background population [41,42]. In the French EPIMAD registry (n=844 patients with EO-IBD), the overall cancer risk was not increased in patients with EO-IBD (standardized incidence ratio [SIR], 0.97; 95% confidence interval [CI], 0.80–1.18), and the risk of colorectal cancer was not increased in patients with either UC or CD [43]. A Danish nationwide cohort reported an elevated cancer risk in patients with CD (SIR, 1.55; 95% CI, 1.29–1.84), but not in those with UC (SIR, 1.12; 95% CI, 0.97–1.28) [44]. Notably, Western studies have consistently demonstrated a higher risk of hematologic malignancies, particularly lymphoproliferative and myeloproliferative disorders [41]. However, an increased risk of colorectal cancer remains controversial [20,45]. This discrepancy likely reflects differences in genetic susceptibility, cancer surveillance practices, environmental exposures, and therapeutic strategies between regions.
Across Asia, EO-IBD is consistently associated with greater healthcare utilization. Korean data demonstrated higher UC-related and all-cause mortality rates in patients with EO-UC than in younger patients with UC (3.5% vs. 0.6% and 12.4% vs. 1.8%, respectively) [32]. In Hong Kong, patients with EO-IBD had higher rates of infection-related hospitalization (odds ratio [OR], 1.87; 95% CI, 1.47–2.38; P<0.001), higher rates of IBD-related hospitalization (OR, 1.09; 95% CI, 1.04–1.15; P=0.001), and longer hospital stays (OR, 1.004; 95% CI, 1.001–1.007; P=0.007) than those with adult-onset IBD [20]. Korean and Japanese studies have demonstrated higher corticosteroid use, greater hospitalization needs, and increased surgical interventions in patients with EO-UC [15,32]. Furthermore, older patients are at a higher risk of opportunistic infections [15,32], including Pneumocystis jirovecii pneumonia, tuberculosis reactivation, and herpes zoster, owing to immunosenescence and polypharmacy. Together, these findings underscore the heavy clinical and healthcare burden of EO-IBD.
CLINICAL CHARACTERISTICS OF EO-IBD IN ASIA
The diagnosis of IBD in older populations presenting with diarrhea, bloody stools, or abdominal pain, can be challenging because IBD is not often considered a likely cause of these symptoms. Many other differential diagnoses are more prevalent than IBD in this age group, including colorectal cancer, diverticular disease, ischemic colitis, and other types of infectious colitis [13]. Consequently, the rate of misdiagnosis at presentation is higher in the older population (60.0%) than in those with younger-onset IBD (15.0%) [46]. Moreover, Kim et al. [18] reported that 34.6% of Korean patients with EO-CD had been prescribed anti-tuberculosis medication prior to their diagnosis of CD, which was significantly higher than that in the late adult-onset group (P<0.001), suggesting a higher likelihood of initial misdiagnosis.
1. Disease Behavior and Location
Patients with EO-IBD typically exhibit distinct characteristics in terms of disease location, extent, and phenotype compared with those with younger IBD (Fig. 1). A systematic review and meta-analysis of 43 studies revealed that the most common disease location in EO-CD was L2 (colon, 44.0% of patients) followed by L1 (ileum, 32.0%) and L3 (ileocolon, 26.0%), respectively [47]. The majority of patients with EO-CD had inflammatory disease behavior (68.0%; 95% CI, 61.0–74.0) [47]. Perianal involvement at diagnosis was infrequent, occurring in 9.0% to 12.0% of patients [47,48]. Other Western studies have reported that left-sided colitis is more prevalent in patients with EO-UC [27,49,50]. In patients with EO-CD, colonic disease and inflammatory disease behavior are more prevalent, whereas penetrating and perianal diseases are less common [27,49,51].
Patients with EO-IBD in Asian countries vary in their disease location, extent, and phenotype. Of the patients with EO-CD in the Korean prospective CONNECT study, more than half exhibited an ileal location (69.2%), which is considerably different from that observed in Western populations [18]. Another Korean study (58.6%) [19] and an Indian study (45.6%) [21] demonstrated similar results with ileal location being more prevalent in patients with EO-CD. Inflammatory disease behavior was most common in Korea (76.9%) [18], Hong Kong (64.3%) [20], and India (63.2%) [21]. A significantly lower proportion of patients with EO-CD had perianal involvement in Korea (11.5%) [18], Hong Kong (5.4%) [20], and India (5.3%) [21] compared with younger patients, who showed rates similar to those in Western populations [18].
The extent of disease at diagnosis in Korean patients with EO-UC was similar to that of younger patients, with nearly half of the patients having proctitis (45.1%) [32]. Data from Hong Kong demonstrated that patients with EO-UC were more likely to present with proctitis (37.4%), followed by left-sided (31.8%), and extensive (30.8%) colitis [20]. In India, data indicate that left-sided colitis is the most common form of EO-UC (59.7%) [21].
In summary, Asian patients with EO-CD are more likely to have ileal involvement, whereas Western patients are more likely to have colonic involvement. However, the prevalence of perianal involvement and inflammatory disease behavior is similar between Asian and Western populations. Patients with EO-UC in Asia are more likely to have proctitis than those in the West, where left-sided colitis is more common; however, this varies by country.
2. Comorbidities and Disease Course
EO-IBD is commonly assumed to have a favorable prognosis; however, the available evidence remains inconclusive. Some studies have suggested that patients with EO-IBD have a poor prognosis, as evidenced by a higher rate of hospitalization and colectomy [32,52]. However, other studies suggest that the prognosis is comparable to that of the young-onset IBD population, evidenced by similar or reduced surgery rates and a reduced probability of disease extension and complicated behavior [18,22,27,53,54].
Age is an important factor that influences disease course. Additionally, aging may be associated with a relative immunosenescence resulting from a decline in both innate and adaptive immunity [55]. Moreover, patients with EO-IBD frequently have or develop comorbidities such as cardiovascular disease, diabetes, renal disease, and malignancies [20,35], and the use of multiple medications for various ailments can augment the risk of drug–drug interactions.
Regarding Asian EO-IBD patients, the Korean prospective CONNECT study revealed that Crohn’s Disease Activity Index at EO-CD diagnosis (124.9±101.9) was significantly lower than that of the late adult-onset group (189.6 ±128.6) (P=0.023). This finding suggests that patients with EO-CD exhibit reduced clinical disease activity at the time of diagnosis. A study in India found that the majority of patients with EO-IBD had moderate disease severity (CD, 64.9%; UC, 69.7%) at the time of diagnosis [21].
Although the disease may appear milder at onset, patients with EO-IBD face higher rates of complications, including infections and hospitalization. A study conducted in Hong Kong reported that patients with EO-UC had higher mortality rates than those with younger-onset disease (7.0% vs. 1.0%; P<0.001); similarly, the mortality rates of UC-related complications were 1.9% and 0.2%, respectively (P=0.017) [36].
However, a Songpa-Kangdong population-based cohort study of Korean patients with EO-UC showed that the disease course in terms of proximal disease extension, hospitalization, and colectomy was similar to that of patients with younger-onset disease [22]. In addition, the Korean prospective CONNECT study revealed the cumulative probability of bowel resection in the EO-CD group tended to be lower than that in the late adult-onset group (P=0.067) [18]. Moreover, the Korean retrospective CONNECT study reported no significant difference in the cumulative probability of bowel resection across age groups. Taken together, these findings suggest that the surgical risk in EO-CD is generally comparable to, or even slightly lower than, that in younger-onset disease [54].
An American retrospective analysis evaluated treatment- and disease-related complications in 2 distinct older IBD populations: patients aged >60 years with adult-onset IBD and those with EO-IBD. The analysis revealed that the risk of disease-related complications did not significantly differ between the 2 groups (adjusted hazard ratio [HR], 0.85; 95% CI, 0.58–1.25), suggesting that the disease courses of these 2 populations were comparable. However, the adult-onset IBD group exhibited a reduced risk of treatment-related complications, including malignancy, mortality, and serious infections (adjusted HR, 0.58; 95% CI, 0.39–0.87) [46]. Therefore, clinicians should balance the anticipated disease course and the risk of serious treatment-associated adverse events (AEs) when treating patients with EO-IBD [46,56].
Despite the limitations of the available data, EO-IBD is likely not milder than younger-onset IBD. Patients and physicians should be aware of the possibility of aggressive disease behaviors even later in life; appropriate treatment decisions should be made based on the potential implications of active disease on associated comorbidities, and disease complications [57]. A recent systematic review (9 studies, 14,765 patients with EO-IBD) compared the natural history and outcomes of EO-IBD to adult-onset IBD based on population-based cohort studies [58]. The cumulative 5-year risk of surgery in patients with EO-CD was 22.6% (95% CI, 18.7–27.2), similar to that of patients with adult-onset CD (RR, 1.04; 95% CI, 0.80–1.34). The cumulative 5-year risk of surgery in patients with EO-UC was 7.8% (95% CI, 5.0%–12.0%), similar to that of patients with adult-onset UC (RR, 1.29; 95% CI, 0.79–2.11). Thus, this study found similar risks of surgery, hospitalization and corticosteroid exposure between these groups, suggesting a similar disease course [58]. A comparison of clinical characteristics and disease burden of EO-IBD between Asian and Western populations is presented in Table 2.
Comparison of Clinical Characteristics of EO-IBD between Asian and Western Countries
TREATMENT STRATEGIES OF EO-IBD IN ASIA
Treating patients with EO-IBD can be challenging. The older population may have several underlying comorbidities, as well as important geriatric features such as frailty and polypharmacy. Polypharmacy is common, with an average of 7 drugs per patient with EO-CD [59]. Therefore, patients with EO-IBD are often undertreated because of safety concerns regarding advanced therapy [60].
1. General Consideration
Although many clinical studies on biologics and novel small-molecule agents for the treatment of IBD are underway, older patients are often excluded from clinical trials. Patients with EO-IBD are usually treated conservatively with consideration of frequent comorbidities, which may increase the risk of treatment-related complications [46,60]. The milder disease course of EO-IBD and the reluctance of physicians to use immunomodulators or biologics may also explain the undertreatment of patients with EO-IBD. An international survey study (424 respondents from 41 countries) demonstrated that physicians avoid the use of thiopurines and anti-tumor necrosis factor-alpha (anti-TNF) agents in older patients with IBD because of concerns regarding lymphoma (94.0%) and opportunistic infections (78.3%) [61].
Therefore, when selecting medication for patients with EO-IBD, it is crucial to consider the effectiveness of the medication and its potential side effects. These side effects may include infections, polypharmacy, drug–drug interactions, and malignancy. Additionally, patients with EO-IBD may have cognitive problems such as dementia, depression, and other neuropsychiatric issues. The nutritional status of patients with EO-IBD is also important for preventing a poor clinical course [62]. Consequently, a multidisciplinary approach is necessary to ensure comprehensive and coordinated care.
2. Infection and Vaccination
Patients with EO-IBD are vulnerable to therapy-related AEs, particularly infections arising from systemic immunosuppression. The annual incidence of serious infections in patients aged ≥65 years who are exposed to immunomodulators or biologics is approximately 5.0% [63]. Vaccination against pneumococcal and influenza infections is strongly recommended for patients with EO-IBD [13,64]. Patients who are >65 years of age and/or immunosuppressed should receive at least 1 dose of pneumococcal vaccine, with revaccination after 5 years; the influenza vaccine should be administered annually [65]. Vaccination against herpes zoster is also recommended, in particular, who would be treated with small molecules such as anti-JAK agents [66].
Furthermore, Asian countries have several unique infection risks, including tuberculosis, cytomegalovirus, and herpes zoster [67]. According to a study conducted in Hong Kong, patients with EO-IBD had higher risks of cytomegalovirus colitis (OR, 3.07; 95% CI, 1.92–4.89; P<0.001), while the risk of herpes zoster was higher numerically (OR, 2.42; 95% CI, 1.22–4.80) but was not statistically significant (P=0.120) [20].
3. Conventional Treatment
The efficacy of 5-aminosalicylic acid (5-ASA), corticosteroids, and immunomodulators do not differ between EO-IBD and younger-onset IBD [13,68].
1) 5-Aminosalicylic Acid
5-ASA is effective in inducing and maintaining remission in patients with mild-to-moderate UC. Interestingly, Target-IBD cohort study demonstrated that older patients with IBD are significantly more likely to receive 5-ASA monotherapy as a treatment for both CD and UC [69].
5-ASA is relatively safe for patients with EO-IBD; however, these patients have a potentially increased risk of nephrotoxicity because of the slower elimination of 5-ASA. Therefore, caution should be exercised when using 5-ASA in patients with EO-IBD and preexisting renal dysfunction, and careful monitoring is warranted [70]. A Korean study showed that 100% of patients with EO-CD were prescribed 5-ASA [18] and a Hong Kong study found that 71.2% of patients with EO-IBD were on 5-ASA at diagnosis [20]. An Indian study demonstrated that 82.6% of the patients with EO-CD and 100% of those with EO-UC were taking 5-ASA [21].
2) Steroids
Steroids are an effective treatment for EO-IBD and are commonly used to induce remission. However, steroids can cause serious side effects, including high blood pressure, diabetes, cataracts, osteoporosis, fractures, sleep disturbances and cognitive impairment. Steroids are also associated with a high risk of serious infections in older patients. Patients with EO-IBD who were administered steroids have a 2.3-fold increased risk of infection compared with non-exposed patients (95% CI, 1.8–2.9) [71]. Nonetheless, steroids are widely used in the treatment of EO-IBD. A multicenter study demonstrated that 31.6% of older patients with IBD (>65 years of age) were prescribed corticosteroids for at least 6 months [59]. The rate of steroid use varies in Asian patients with EO-IBD. Nearly half (46.2%) of Korean patients with EO-CD received steroid treatment [18], however, only 30.3% of Korean patients with EO-UC were treated with steroids [22]. A Hong Kong study revealed that 23.8% of patients with EO-IBD received steroid treatment [20], whereas an Indian study reported that 68.4% of patients with EO-CD and 40.3% of those with EO-UC were treated with steroids [21].
3) Immunomodulators
Immunomodulators including thiopurines and methotrexate, may be indicated for patients with EO-IBD to maintain remission, especially in those with steroid dependence. However, the use of immunomodulators is associated with a higher risk of opportunistic infections and other serious adverse effects, such as a higher risk of malignancy.
Thiopurines have been shown to be equally effective in patients with EO-IBD and younger adults [68]. However, thiopurine may increase the risk of non-Hodgkin’s lymphoma, and the risk of lymphoma increases with age [56,72]. In a French cohort study, the incidence of lymphoma was significantly higher in older patients with IBD taking thiopurines compared with those ≤ 50 years of age (5.41 vs. 0.37 per 1,000 person-years) [72]. In addition, thiopurine use is strongly associated with infections and other AEs in older patients with IBD. When comparing thiopurine-related AEs in patients who started thiopurines at >60 years of age with those that started at 18–50 years of age, a significantly higher risk of infection was noted in the older group (3.6% vs. 2.0%; P<0.001) [73]. Moreover, patients starting thiopurines at >60 years of age had higher rates of all types of myelotoxicity, digestive intolerance, and hepatotoxicity, leading to a higher rate of discontinuation when compared with the younger group (67.2% vs. 63.1%; P<0.001) [73]. Indeed, physicians are reluctant to use immunomodulators in older patients, and a retrospective study of 393 patients with EO-IBD (aged >65 years) showed that only 5.6% were on thiopurines and 1.0% were on methotrexate [59].
A Korean study also reported that immunomodulators were used less frequently in the EO-CD group (48.1%) than in the non-EO-CD group (87.0%; P<0.001) [19]. Additionally, an Indian study reported significantly lower rates of thiopurine use in EO-UC (10.1%) and EO-CD (10.5%) than in non-EO-UC (39.9%; P<0.001) and non-EO-CD (72.1%; P<0.001) [21].
4) Advanced Therapy
In clinical practice, biologics and small molecules are underutilized in the EO-IBD population. Increased toxicity and decreased efficacy are major concerns in the older population. Several studies have shown that the use of immunomodulators or biologics is lower in patients with EO-IBD. Among the 841 patients with EO-IBD in a French cohort, only 7.0% were treated with anti-TNF agents and 16.0% with immunomodulators [27]. The Target-IBD cohort study evaluated the medication utilization pattern and revealed that older patients with IBD were less frequently prescribed anti-TNF agents than younger patients [69].
In Asian countries, Kim et al. [18] reported that patients with EO-CD were significantly less likely to use anti-TNF agents than younger patients (P=0.047). A Hong Kong study presented similar results, demonstrating that patients with EO-IBD had a significantly lower cumulative use of biologics (P=0.040) [20]. In contrast, a Korean population-based study found that the cumulative risks of anti-TNF use were not different between the EO-UC and non-EO-UC groups (P=0.095) [22].
No differences in the efficacies of biologics have been reported for EO-IBD [13]. Indeed, the data are conflicting regarding the efficacy of biologics in the older population. A multicenter observational study comparing the efficacy of anti-TNF agents between patients with EO-IBD and older patients with non-EO-IBD found that, after 52 weeks of anti-TNF treatment, clinical and steroid-free remission rates were significantly lower in those with EO-IBD (37.7% vs. 60.8%, P=0.001 and 35.9% vs. 57.8%, P=0.003, respectively) [74]. Multivariate analysis revealed that elderly onset was a significant factor for both clinical remission (OR, 0.49; 95% CI, 0.25–0.96) and steroid-free remission (OR, 0.51; 95% CI, 0.26–0.99). However, in a meta-analysis of 4 randomized controlled trials of patients with UC (n=231, aged ≥ 60 years), the effect of anti-TNF agents was similar for induction of remission (OR, 1.05; 95% CI, 0.33–3.39) and maintenance of remission (OR, 0.49; 95% CI, 0.18–1.33) between older and younger patient groups [75].
Several studies on the safety of biologics including anti-TNF agents in older adults have been published. In a meta-analysis of autoimmune diseases treated with biologics (4,719 biologic users aged ≥60 years; 13,305 biologics users aged <60 years; 3,961 biologics non-users aged ≥60 years), the rates of all infections were higher in older biologic users than in younger biologics users (13.0% vs. 6.0%; OR, 2.28; 95% CI, 1.57–3.31); infection rates were also higher in older biologic users than in biologic non-users (OR, 3.60; 95% CI, 1.62–8.01) [76]. Another study including a total of 895 patients with IBD (age at anti-TNF initiation: <40 years [n=546, 61.0%], 40–59 years [n=268, 29.9%], and ≥ 60 years [n=81, 9.1%]) determined that treatment failure rates were higher in the older group (subhazard rate for age ≥60 years, 1.46). The subhazard rate in the older group (≥60 years) was 1.52 for discontinuation because of AEs and 1.11 for lack of effectiveness [77].
In summary, these findings suggest that anti-TNF agents have similar or slightly reduced effects in older patients with IBD compared with younger adults. However, older adults are at a higher risk of AEs, including infections, owing to age-related factors. Therefore, given their effectiveness, anti-TNF agents should be considered when necessary, despite the risk of infection.
Vedolizumab is the preferred first-line agent for treating older patients with IBD and steroid-dependent moderate-to-severe UC [61]. Vedolizumab is considered relatively safe biologics, because it is gut-specific. A post hoc analysis of GEMINI trials showed that safety profiles of vedolizumab and placebo were similar in all age groups, even in patients aged ≥ 55 years [78]. Regarding the efficacy of vedolizumab, a real-world retrospective cohort study revealed the similar efficacy of vedolizumab for the younger and elderly groups in terms of durability during the 6- to 12-month period after initiation (46.8% vs. 40.1%; P=0.237) [79]. Therefore, vedolizumab can be considered a safe option in EO-IBD patients.
Data on the use of ustekinumab in older patients with IBD is limited. Regarding efficacy, a retrospective real-world study showed that nearly 90% patients in older and younger CD patients experienced clinical response; however, the older group was less likely to achieve complete clinical remission (28.2% vs. 52.6%; P=0.010) [80]. In the UNITI and UNIFI studies, the risk of serious AEs or infections was not increased at any age [81,82]. Thus, ustekinumab may be a suitable alternative in patients with EO-IBD who have an increased risk of infection.
Tofacitinib is an effective agent for treating moderately to severely active UC. However, AEs including reactivation of herpes zoster and venous thromboembolism, have been reported, and increasing age seems to be a risk factor. Therefore, the use of tofacitinib in patients with EO-IBD should be carefully considered [83].
CONCLUSIONS
The aging population in Asia has led to an increase in the prevalence of EO-IBD, and this trend is anticipated to persist. The prevalence of ileal involvement is notable among Asian patients with EO-CD, a phenomenon that contrasts with Western patients, where colonic involvement is more common. Furthermore, differentiating patients with EO-CD from those with tuberculous enterocolitis is imperative in Asia. Although EO-IBD often manifests with a milder clinical course at diagnosis, it poses distinct diagnostic and therapeutic challenges. Optimizing care will require the integration of age-specific risk assessments, comorbidity management, and the cautious yet effective use of biologics and small molecules. Phenotypic differences, such as disease location, between Western and Asian populations may explain the subsequent disparities in the natural history of patients with EO-IBD. Consequently, treatment policies for Asian patients with EO-IBD may require adaptation from those established in Western countries. Therefore, real-world efficacy and safety data on biologics and small molecules in Asian patients with EO-IBD are essential. Furthermore, the development of evidence-based guidelines for patients with EO-IBD in Asia requires regional collaboration.
Notes
Funding Source
This work was supported by a grant (No. 2025-02) from the Kangdong Sacred Heart Hospital Fund.
Conflict of Interest
Kim YS is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.
Data Availability Statement
Data sharing is not applicable as no new data were created or analyzed in this study.
Author Contributions
Conceptualization: Kim YS. Data curation: Kim YS. Data interpretation: Yoon J, Kim D. Formal analysis: Yoon J, Kim D, Kim YS. Supervision: Kim YS. Writing - orginal draft: Yoon J, Kim YS. Writing - review & editing: all authors. Approval of final manuscript: all authors.