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Purpose To assess safety and effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in IBD patients ≥ 60 years. Methods Ninety IBD patients ≥ 60 years at initiation of anti-TNF therapy, 145 IBD patients ≥ 60 years without anti-TNF therapy and 257 IBD patients < 60 years at initiation of anti-TNF therapy were retrospectively included in this multicentre study. Primary outcome was the occurrence of severe adverse events (SAEs), serious infections and malignancies. Secondary outcome was effectiveness of therapy. Cox regression analyses were used to assess differences in safety and effectiveness. In safety analyses, first older patients with and without anti-TNF therapy and then older and younger patients with anti-TNF therapy were assessed. Results In older IBD patients, the use of anti-TNF therapy was associated with serious infections (aHR 3.920, 95% CI 1.185–12.973, p = .025). In anti-TNF-exposed patients, cardiovascular disease associated with serious infections (aHR 3.279, 95% CI 1.098–9.790, p = .033) and the presence of multiple comorbidities (aHR 9.138 (1.248–66.935), p = .029) with malignancies, while patient age did not associate with safety outcomes. Effectiveness of therapy was not affected by age or comorbidity. Conclusion Older patients receiving anti-TNF therapy have a higher risk of serious infections compared with older IBD patients without anti-TNF therapy, but not compared with younger patients receiving anti-TNF therapy. However, in anti-TNF-exposed patients, comorbidity was found to be an indicator with regards to SAEs. Effectiveness was comparable between older and younger patients.

BACKGROUND & AIMS: We aimed to perform geriatric assessment in older patients with inflammatory bowel disease (IBD) to evaluate which IBD characteristics associate with deficits in geriatric assessment and the impact of deficits on disease burden (health-related quality of life).METHODS: A prospective multicenter cohort study including 405 consecutive outpatient patients with IBD aged ≥65 years. Somatic domain (comorbidity, polypharmacy, malnutrition), impairments in (instrumental) activities of daily living, physical capacity (handgrip strength, gait speed), and mental (depressive symptoms, cognitive impairment) and social domain (life-partner) were assessed. Deficits in geriatric assessment were defined as ≥2 abnormal domains; 2-3 moderate deficits and 4-5 severe deficits. Clinical (Harvey Bradshaw Index >4/partial Mayo Score >2) and biochemical (C-reactive protein ≥10 mg/L and/or fecal calprotectin ≥250 μg/g) disease activity and disease burden (short Inflammatory Bowel Disease Questionnaire) were assessed.RESULTS: Somatic domain (51.6%) and activities of daily living (43.0%) were most frequently impaired. A total of 160 (39.5%) patients had moderate deficits in their geriatric assessment; 32 (7.9%) severe. Clinical and biochemical disease activity associated with deficits (clinical: adjusted odds ratio, 2.191; 95% confidence interval, 1.284-3.743; P = .004; biochemical: adjusted odds ratio, 3.358; 95% confidence interval, 1.936-5.825; P < .001). Deficits in geriatric assessment independently associate with lower health-related quality of life.CONCLUSION: Deficits in geriatric assessment are highly prevalent in older patients with IBD. Patients with active disease are more prone to deficits, and deficits associate with lower health-related quality of life, indicating higher disease burden. Prospective data validating impact of frailty and geriatric assessment on outcomes are warranted to further improve treatment strategies.

Background: Few data are available on the effects of age and comorbidity on treatment outcomes of vedolizumab and ustekinumab in inflammatory bowel disease (IBD).Aims: To evaluate the association between age and comorbidity with safety and effectiveness outcomes of vedolizumab and ustekinumab in IBD.Methods: IBD patients initiating vedolizumab or ustekinumab in regular care were enrolled prospectively. Comorbidity prevalence was assessed using the Charlson Comorbidity Index (CCI). Association between age and CCI, both continuously assessed, with safety outcomes (any infection, hospitalisation, adverse events) during treatment, and effectiveness outcomes (clinical response and remission, corticosteroid-free remission, clinical remission combined with biochemical remission) after 52 weeks of treatment were evaluated. Multivariable logistic regression was used to adjust for confounders.Results: We included 203 vedolizumab- and 207 ustekinumab-treated IBD patients, mean age 42.2 (SD 16.0) and 41.6 (SD 14.4). Median treatment duration 54.0 (IQR 19.9-104.0) and 48.4 (IQR 24.4-55.1) weeks, median follow-up time 104.0 (IQR 103.1-104.0) and 52.0 weeks (IQR 49.3-100.4). On vedolizumab, CCI associated independently with any infection (OR 1.387, 95% CI 1.022-1.883, P = 0.036) and hospitalisation (OR 1.586, 95% CI 1.127-2.231, P = 0.008). On ustekinumab, CCI associated independently with hospitalisation (OR 1.621, 95% CI 1.034-2.541, P = 0.035). CCI was not associated with effectiveness, and age was not associated with any outcomes.Conclusions: Comorbidity - but not age - is associated with an increased risk of hospitalisations on either treatment, and with any infection on vedolizumab. This underlines the importance of comorbidity assessment and safety monitoring of IBD patients.

Background The population of older patients with inflammatory bowel diseases (IBD) is increasing. Treating older patients is challenging as they are characterised by heterogeneity in geriatric domains, such as functional, social or mental status. Although treatment guidelines do not distinguish between older and adult patients with IBD, several studies have found a difference in applied treatment strategies. It is unknown which considerations contribute to this. Therefore, we performed semi-structured interviews with IBD gastroenterologists and IBD nurses to assess a) which patient characteristics they consider and b) which treatment goals they pursue in older IBD patients, compared with adult IBD patients and c) what view they have on prescribing IBD medications in older IBD patients. Methods IBD gastroenterologists and IBD nurses practicing throughout The Netherlands were asked to participate. Purposive sampling ensured a heterogenous population. Interviews took place in May or July 2019 were audio recorded and conducted face to face. Two researchers coded the verbatim transcripts independently. Codes and themes were obtained inductively and were finalised in consensus. Recruitment was stopped when no new information came out of three consecutive interviews. Results Ten gastroenterologists and five IBD nurses were included: eight females, median age 43 years (34–61), median years of experience in IBD care, eight years (1–20), three working in an academic centre. Comorbidity and polypharmacy were most frequently mentioned as important patient characteristics in the choice of treatment of IBD in older patients. Only when asked specifically, participants mentioned characteristics of frailty, of which self-dependence, mobility, and cognitive impairment most often. However, applying ‘a clinical view’ or ‘gut feeling’ were frequently mentioned and none of the participants assessed frailty systematically. Therapy goals in older patients differed from those in adult patients: participants indicated to pursue clinical remission more often than endoscopic remission. Most participants stated to be reluctant to prescribe thiopurines. Other opinions about preferred medication differed remarkably, especially regarding low dose prednisone maintenance therapy. Conclusion In the treatment of older IBD patients, attention is paid to comorbidity and polypharmacy, but geriatric characteristics, such as functional or cognitive impairment or frailty are barely taken into consideration. Clinicians put lower priority on pursuing endoscopic remission in older compared with younger patients. The large variation in clinicians’ treatment preferences reflects a lack of evidence regarding treatment of older patients with IBD.

Background The population of older patients with Inflammatory Bowel Diseases (IBD) is expanding. Knowledge on the prevalence and impact of geriatric impairments is scarce in this heterogenous group. In other fields of medicine, it has been established that geriatric impairments associate with adverse outcomes. Therefore, the aims of our study were to assess the prevalence of geriatric impairments in older IBD patients and to evaluate the association between geriatric impairments and disease burden of IBD through the short Inflammatory Bowel Disease Questionnaire (sIBDQ). Methods Consecutive IBD patients aged ≥65 years were included at outpatient departments and infusion centres of four hospitals in The Netherlands. Comorbidity, polypharmacy and malnutrition (somatic domain), cognitive impairment and depressive symptoms (mental domain), handgrip strength and gait speed (physical domain) and impairments in (instrumental) activities of daily living ((I)ADL) (functional domain) were assessed. Disease activity was assessed through Harvey Bradshaw Index (HBI) or partial Mayo Score (pMS) (remission: HBI Results In total, 336 patients were included: median age 70.0 (IQR 67.0–73.0); 161 CD (47.9%); 71 active disease (21.1%); mean sIBDQ 59.7 (SD 8.1). Prevalence of geriatric impairments is tabulated (Table 1). Both active disease and the presence of two or more impaired domains were statistically significantly and independently associated with a higher disease burden (lower sIBDQ) (Table 2). Conclusion In an older IBD patient population, geriatric impairments are frequently encountered and associate with a higher disease burden. These results are a call for more research on the relationship between geriatric impairments and IBD disease burden to improve patient care in older IBD patients.

Background The population of older patients with inflammatory bowel disease [IBD] is increasing. Patient age does not fully account for poor outcomes and its clinical utility for risk stratification is limited. Comprehensive geriatric assessment [CGA], comprising a somatic, functional, mental, and social assessment or frailty, could be a predictor tool. Aims To systematically review literature on the kind of components of a CGA being used in adult IBD patients and the association of these components with adverse health outcomes. Methods An electronic literature search was performed on January 16, 2018, using PubMed, Embase, Web of Science, the Cochrane Library, CENTRAL, Emcare, and PsycINFO. Longitudinal studies relating somatic, functional, mental, and social assessment or frailty to adverse health outcomes during follow-up in IBD patients were included. The Newcastle-Ottawa scale was used to assess individual study quality. Results Of 4080 identified citations, 27 studies were included, reporting 169 associations. Median sample size was 108 patients (interquartile range [IQR] 60–704). No studies performed subgroup analyses on older patients, and the highest mean age reported was 52.7 years. Somatic and functional assessments were used in three studies, mental in 24, and social in five. No study assessed cognitive status, functional performance, or frailty. In 62 associations [36.7%], components of a CGA were significantly associated with adverse health outcome measurements. Conclusions Components of a CGA were associated with adverse health outcomes in IBD patients, but older patients were under-represented. More studies among older patients with IBD are warranted to further establish the clinical impact of a CGA.

Both γδ T cells and CD4+ T cells have been implicated in immunity to malaria, but their association with natural gain or loss of infection has not been studied before. Therefore, we followed up asymptomatic children living in an area endemic for malaria in Indonesia for 21 months. The percentage of γδ T cells was related to both current and previous infection, with higher percentages in infected than uninfected children and declining after infections resolve. Infected children also had higher levels of Th1 and Th17 cells, lower levels of CD25Hi FOXP3+ regulatory T cells (Tregs), but similar levels of Th2 cells as compared to uninfected children. However, TNF, IFN-γ, and IL-17 cytokine responses to Plasmodium falciparum-infected red blood cells (PfRBCs) were similar, while IL-5 and IL-13 responses were lower in infected children. Furthermore, infected children had more phenotypically exhausted PD-1+ CD4+ T cells, more Tregs expressing TNF-RII, and higher IL-10 responses to PfRBCs, which persisted following resolution of infection. Altogether, this study demonstrates that asymptomatic malaria infection is associated with some long-lasting changes in the frequencies and immunoregulation of circulating innate and adaptive T cells, which might in part explain how pre-exposure to malaria affects responses to subsequent immunological challenges.