Frailty screening associates with hospitalization and decline in quality of life and functional status in older patients with inflammatory bowel disease.

BACKGROUND AND AIMS: To study frailty screening in association with hospitalization and decline in quality of life (QoL) and functional status in older patients with Inflammatory Bowel Diseases (IBD). METHODS: A prospective multicentre cohort study in IBD patients ≥65 years using frailty screening (G8 Questionnaire). Outcomes were all-cause, acute and IBD-related hospitalization, any infection, any malignancy, QoL (EQ5D-3L) and functional decline (Instrumental Activities of Daily Living, (IADL)) during 18 months follow-up. Confounders: age, IBD type, biochemical disease activity (C-reactive protein ≥10 mg/L and/or fecal calprotectin ≥250 µg/g), comorbidity (Charlson Comorbidity Index). RESULTS: Out of 405 patients, median age 70 years, 196 (48%) screened at risk for frailty. All-cause hospitalizations occurred 136 times in 96 patients (23.7%), acute hospitalizations 103 times in 74 (18.3%). Risk of frailty did not associate with all-cause (aHR 1.5, 95% CI 0.9-2.4), but did associate with acute hospitalizations (aHR 2.2, 95% CI 1.3-3.8). Infections occurred in 86 patients (21.2%) and were not associated with frailty. Decline in QoL was experienced by 108 (30.6%) patients, decline in functional status by 46 (13.3%). Frailty screening associated with decline in QoL (aOR 2.1, 95% CI 1.3-3.6) and functional status (aOR 3.7, 95% CI 1.7-8.1). CONCLUSIONS: Frailty screening associates with worse health outcomes in older patients with IBD. Further studies are needed to assess feasibility and effectiveness of implementation in routine care.

Deficits in Geriatric Assessment Associate With Disease Activity and Burden in Older Patients With Inflammatory Bowel Disease.

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.

Control Crohn Safe with episodic adalimumab monotherapy as first-line treatment study (CoCroS): study protocol for a randomised controlled trial.

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory bowel disease with a heterogeneous clinical presentation, relapse rate and treatment response. At present, no markers are available to adequately predict disease course at diagnosis. To prevent overtreatment of patients with a relative mild disease course, a step-up approach starting with corticosteroids is usually applied. Timely introduction of potentially disease modifying drugs and tight control of mucosal inflammation are crucial to prevent disease-related complications in patients with a complex disease course. We hypothesise that episodic treatment with adalimumab monotherapy in combination with close monitoring after drug discontinuation improves long-term outcome and reduces drug-related side effects, while preventing overtreatment. METHODS AND ANALYSIS: In this pragmatic multicentre randomised controlled trial, newly diagnosed CD patients or CD patients with a flare, naïve to thiopurines and biologicals, will be included and randomised 1:1 to open-label episodic (ie, 24 weeks) adalimumab monotherapy or step-up care starting with corticosteroids. The primary outcome is the number of yearly quarters of corticosteroid free clinical (Monitor Inflammatory Bowel Disease At Home score ≤3) and biochemical (C reactive protein within normal range and faecal calprotectin ≤200 µg/g) remission at week 96. Secondary outcomes are total healthcare costs, cumulative corticosteroid dose, proportion of patients with endoscopic remission at week 24, corticosteroid-free clinical remission, time to remission and patient-reported outcome measures on quality of life, (work) disability and treatment adherence. Safety outcomes are drug-related and disease-related adverse events and disease progression on MRI-enterography at week 96. ETHICS AND DISSEMINATION: This study is approved by the Medical Research Ethics Committee of azM/UM in Maastricht dated 21 August 2019 (METC18-076) and is monitored by the Clinical Trial Centre Maastricht according to Good Clinical Practice guidelines. Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT03917303.

Ustekinuma b for Crohn's Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, a Nationwide Prospective Observational Cohort Study.

AIMS: Ustekinumab is a monoclonal antibody that selectively targets p40, a shared subunit of the cytokines interleukin [IL]-12 and IL-23. It is registered for the treatment of inflammatory bowel diseases. We assessed the 2-year effectiveness and safety of ustekinumab in a real world, prospective cohort of patients with Crohn's disease [CD]. METHODS: Patients who started ustekinumab were prospectively enrolled in the nationwide Initiative on Crohn and Colitis [ICC] Registry. At weeks 0, 12, 24, 52 and 104, clinical remission Harvey Bradshaw Index≤ 4 points], biochemical remission (faecal calprotectin ≤ 200 µg/g and/or C-reactive protein ≤5 mg/L], perianal fistula remission, extra-intestinal manifestations, ustekinumab dosage and safety outcomes were determined. The primary outcome was corticosteroid-free clinical remission at week 104. RESULTS: In total, 252 CD patients with at least 2 years of follow-up were included. Of all included patients, the proportion of patients in corticosteroid-free clinical remission was 32.3% [81/251], 41.4% [104/251], 39% [97/249] and 34.0% [84/247] at weeks 12, 24, 52 and 104, respectively. In patients with combined clinical and biochemical disease activity at baseline [n = 122], the corticosteroid-free clinical remission rates were 23.8% [29/122], 35.2% [43/122], 40.0% [48/120] and 32.8% [39/119] at weeks 12, 24, 52 and 104, respectively. The probability of remaining on ustekinumab treatment after 52 and 104 weeks in all patients was 64.3% and 54.8%, respectively. The main reason for discontinuing treatment after 52 weeks was loss of response [66.7%]. No new safety issues were observed. CONCLUSION: After 104 weeks of ustekinumab treatment, one-third of CD patients were in corticosteroid-free clinical remission.

Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab- and ustekinumab-treated patients with inflammatory bowel disease-a prospective multicentre cohort study.

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.

Ustekinumab is associated with superior effectiveness outcomes compared to vedolizumab in Crohn's disease patients with prior failure to anti-TNF treatment.

BACKGROUND: Both vedolizumab and ustekinumab can be considered for the treatment of Crohn's disease (CD) when anti-TNF treatment fails. However, head-to-head trials are currently not available or planned. AIM: To compare vedolizumab and ustekinumab in Crohn´s disease patients in a prospective registry specifically developed for comparative studies with correction for confounders. METHODS: Crohn´s disease patients, who failed anti-TNF treatment and started vedolizumab or ustekinumab in standard care as second-line biological, were identified in the observational prospective Dutch Initiative on Crohn and Colitis Registry. Corticosteroid-free clinical remission (Harvey Bradshaw Index ≤4), biochemical remission (C-reactive protein ≤5 mg/L and fecal calprotectin ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, and safety outcomes were compared after 52 weeks of treatment. To adjust for confounding and selection bias, we used multiple logistic regression and propensity score matching. RESULTS: In total, 128 vedolizumab- and 85 ustekinumab-treated patients fulfilled the inclusion criteria. After adjusting for confounders, ustekinumab-treated patients were more likely to achieve corticosteroid-free clinical remission (odds ratio [OR]: 2.58, 95% CI: 1.36-4.90, P = 0.004), biochemical remission (OR: 2.34, 95% CI: 1.10-4.96, P = 0.027), and combined corticosteroid-free clinical and biochemical remission (OR: 2.74, 95% CI: 1.23-6.09, P = 0.014), while safety outcomes (infections: OR: 1.26, 95% CI: 0.63-2.54, P = 0.517; adverse events: OR: 1.33, 95% CI: 0.62-2.81, P = 0.464; hospitalisations: OR: 0.67, 95% CI: 0.32-1.39, P = 0.282) were comparable between the two groups. The propensity score matched cohort with sensitivity analyses showed comparable results. CONCLUSIONS: Ustekinumab was associated with superior effectiveness outcomes when compared to vedolizumab, while safety outcomes were comparable after 52 weeks of treatment in CD patients who have failed anti-TNF treatment.

The reproducibility of skeletal muscle signal intensity on routine magnetic resonance imaging in Crohn's disease.

BACKGROUND AND AIM: Myosteatosis is a prognostic factor in cancer and liver cirrhosis. It can be determined noninvasively using computed tomography or, as shown recently, by magnetic resonance (MR) imaging. The primary aim was to analyze the reproducibility of skeletal muscle signal intensity on routine MR-enterographies, as indicator of myosteatosis, in Crohn's disease (CD) and to explore the association between skeletal muscle signal intensity at diagnosis with time to intestinal resection. METHODS: CD patients undergoing MR-enterography within 6 months from diagnosis and having a maximum of 5 years follow-up were included. Skeletal muscle signal intensity was analyzed on T1-weighted fat-saturated post-contrast images. Intra-observer and inter-observer reproducibilities were assessed by intra-class correlation coefficient and Cohen's kappa. Intra-observer and inter-observer variabilities were determined by Pearson correlation coefficient and displayed by Bland-Altman plots. Time to intestinal resection was studied by Kaplan-Meier analysis. RESULTS: Median time between diagnosis and MR-enterography was 5 weeks (inter-quartile range 1-9) in 35 CD patients. Skeletal muscle signal intensity showed good intra-class correlation and substantial agreement (for intra-observer, intraclass correlation coefficient = 0.948, κ = 0.677; and inter-observer reproducibility, intraclass correlation coefficient = 0.858, κ = 0.622). Resection free survival was shorter in the low skeletal muscle signal intensity group (P = 0.037). CONCLUSION: Skeletal muscle signal intensity on routine MR-enterographies is reproducible and was associated with unfavorable disease outcome, indicating potential clinical relevance.

Ustekinumab for Crohn's Disease: Results of the ICC Registry, a Nationwide Prospective Observational Cohort Study.

BACKGROUND AND AIMS: Ustekinumab is approved for the treatment of Crohn's disease [CD]. Systematically registered prospective real-world data are scarce. We therefore aimed to study the effectiveness, safety and usage of ustekinumab for CD in everyday practice. METHODS: We prospectively enrolled CD patients initiating ustekinumab in regular care between December 2016 and January 2019. Clinical (Harvey Bradshaw Index [HBI]), biochemical (C-reactive protein [CRP] and faecal calprotectin [FCP]), extra-intestinal manifestations and, peri-anal fistula activity, ustekinumab dosage, concomitant medication use, and adverse events were documented at weeks 0, 12, 24, and 52. The primary outcome was corticosteroid-free clinical remission. RESULTS: In total, 221 CD patients were included (98.6% anti-tumour necrosis factor [TNF] and 46.6% vedolizumab exposed) with a median follow-up of 52.0 weeks [interquartile range 49.3-58.4]. Corticosteroid-free clinical remission rates at weeks 24 and 52 were 38.2% and 37.1%, respectively. An initial dosing schedule of 8 weeks, compared to 12 weeks, correlated with a lower discontinuation rate [20.0% vs 42.6%, p = 0.01], but comparable corticosteroid-free clinical remission at week 52 (46.3% [q8w] vs 34.6% [q12w], p = 0.20). There was no clinical benefit of combination therapy after 52 weeks when compared to ustekinumab monotherapy [combi 40.6% vs mono 36.0%, p = 0.64]. At baseline, 28 patients had active peri-anal fistula, of whom 35.7% showed complete clinical resolution after 24 weeks. During follow-up we encountered six severe infections [3.5 per 100 patient-years], with all patients being on concomitant immunosuppressant therapies. Ustekinumab treatment discontinuation was observed in 75 [33.9%] patients mainly due to lack of response. CONCLUSION: Ustekinumab is a relatively safe and effective treatment option for CD patients with prior failure of anti-TNF and anti-integrin therapies.

Vedolizumab for Inflammatory Bowel Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, A Nationwide Prospective Observational Cohort Study: ICC Registry - Vedolizumab.

Prospective data of vedolizumab treatment for patients with inflammatory bowel disease (IBD) beyond 1 year of treatment is scarce but needed for clinical decision making. We prospectively enrolled 310 patients with IBD (191 with Crohn's disease (CD) and 119 patients with ulcerative colitis (UC)) with a follow-up period of 104 weeks (interquartile range: 103-104) in a nationwide registry. The corticosteroid-free clinical remission rate (Harvey Bradshaw Index ≤ 4, Short Clinical Colitis Activity index ≤ 2) at weeks 52 and 104 were 28% and 19% for CD and 27% and 28% for UC, respectively. Fifty-nine percent maintained corticosteroid-free clinical remission between weeks 52 and 104. Vedolizumab with concomitant immunosuppression showed comparable effectiveness outcomes compared with vedolizumab monotherapy (week 104: 21% vs. 23%; P = 0.77), whereas 8 of 13 severe infections occurred in patients treated with concomitant immunosuppression. To conclude, the clinical effect was 19% for CD and 28% for UC after 2 years of follow-up regardless of concomitant immunosuppression.

Novel Perceived Stress and Life Events Precede Flares of Inflammatory Bowel Disease: A Prospective 12-Month Follow-Up Study.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] is characterized by recurrent disease flares. The impact of psychosocial wellbeing on the occurrence of flares is unclear. In this prospective study, we aimed to evaluate the association between patient-reported psychosocial wellbeing and disease flares using continuous monitoring. METHODS: Consecutive IBD patients were recruited from the myIBDcoach telemedicine study cohort. Over 12 months, participants reported on disease activity together with anxiety, depression, fatigue, perceived stress and life events every 1-3 months. Flares were defined using a combination of clinical disease activity and additional measurements. Generalized estimating equation models were used to assess associations between psychosocial wellbeing and flares over time. The influences of both the presence of psychosocial symptoms in general as well as novel psychosocial symptoms were analysed. RESULTS: In total, 417 patients were included. Forty-nine patients [11.8%] experienced a flare during the study period. The occurrence of life events in the preceding 3 months was positively associated with flares (odds ratio [OR] = 1.81; 95% confidence interval [CI] = 1.04-3.17), while the presence of anxiety, depression, fatigue and perceived stress in general was not. However, novel perceived stress [OR = 2.92; 95% CI = 1.44-5.90] was associated with flares. CONCLUSIONS: The occurrence of life events and novel perceived stress are associated with disease flares in the next 3 months, while the presence of perceived stress in general is not. These findings underline the importance of continuous personalized monitoring of IBD patients and may contribute to the prevention of disease flares.

Liver test abnormalities predict complicated disease behaviour in patients with newly diagnosed Crohn's disease.

BACKGROUNDS: In coeliac disease, the prevalence of liver test abnormalities (LTAs) is higher in patients with more severe mucosal inflammation. In Crohn's disease, prognosis is related to the severity of mucosal inflammation. AIM: The aim of this study was to investigate whether the presence of LTA predicts the occurrence of complicated disease behaviour in newly diagnosed Crohn's disease. METHODS: A retrospective cohort study was performed in patients newly diagnosed with Crohn's disease between 2002 and 2011. The complicated disease was defined as the occurrence of stricturing and/or perforating disease. LTAs were defined as a value of any of alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), or alanine aminotransferase (ALT) over the upper limit of normal. RESULTS: Three hundred eighty-three patients were included, of whom 34.1% had LTA. LTAs were mostly mild (less than two times the upper limit of normal). During the 5-year follow-up, 33.1% of patients in the group with LTA developed complicated disease behaviour compared to 14.6% in patients without LTA (p < 0.001). The presence of LTA was identified as a risk factor for complicated disease behaviour (HR 2.6, 95% confidence interval (CI) 1.5-4.2, p < 0.0001). CONCLUSIONS: In newly diagnosed Crohn's disease, the presence of LTA was an independent risk factor for the development of complicated disease behaviour.

Gastric volume changes in response to a meal: validation of magnetic resonance imaging versus the barostat.

PURPOSE: To determine the accuracy of magnetic resonance imaging (MRI) volume scans: 1) to measure known meal volumes in vitro, and 2) to compare volume changes in response to a meal measured with the barostat with those measured with MRI in vivo. MATERIALS AND METHODS: Polyethylene bags were filled with known volumes and MRI volume scans were performed to determine the accuracy of the volume measurements. Barostat measurements and MRI volume scans were performed simultaneously in 14 healthy subjects before and up to 90 minutes after ingestion of a liquid meal. RESULTS: In vitro MRI-determined volumes showed an excellent linear relationship (r = 0.995, P < 0.001) with actual meal volumes. Although fasting gastric volume, postprandial gastric volume, and relaxation volume measured with MRI were significantly larger compared to volumes measured with the barostat, volumes determined with both techniques showed excellent correlation. CONCLUSION: Volumes in the range of postprandial meal volumes are accurately measured with MRI. MRI is a noninvasive technique to measure stomach volumes and volume changes in response to a meal. Volume changes in response to a meal measured with MRI correlate perfectly with those measured with the barostat device.

Gastric accommodation and motility are influenced by the barostat device: Assessment with magnetic resonance imaging.

The barostat is considered the gold standard for evaluation of proximal gastric motility especially for the accommodation response to a meal. The procedure is invasive because it involves the introduction of an intragastric catheter and bag and is not always well tolerated. Moreover, the barostat bag itself may influence motility. Nowadays magnetic resonance imaging (MRI) is able to measure several aspects of gastric motility noninvasively. To evaluate whether the accommodation response of the stomach, observed with the barostat, is present during MRI and whether the barostat interferes with gastric physiology, gastric accommodation, motility, and emptying were studied twice in 14 healthy subjects with MRI using three-dimensional volume scans and two-dimensional dynamic scans once in the presence of a barostat bag and once when the barostat bag was not present. Fasting and postprandial intragastric volumes were significantly higher in the experiment with barostat vs. without barostat (fasting: 350 +/- 132 ml vs. 37 +/- 21 ml, P < 0.0001; postprandial: 852 +/- 126 ml vs. 361 +/- 62 ml, P < 0.0001). No significant differences were found in gastric emptying (88 +/- 41 vs. 97 +/- 40 ml/h, not significant) and contraction frequency between both experiments. The accommodation response observed in the presence of the barostat bag was not observed in the absence of the barostat bag. In conclusion, the presence of an intragastric barostat bag does not interfere with gastric emptying or motility, but the accommodation response measured with the barostat in situ is not observed without the barostat bag in situ. Gastric accommodation is a nonphysiological barostat-induced phenomenon.