Systematic review: Patient-related, microbial, surgical, and histopathological risk factors for endoscopic post-operative recurrence in patients with Crohn's disease.

BACKGROUND: Risk stratification for endoscopic post-operative recurrence (ePOR) in Crohn's disease (CD) is required to identify patients who would benefit most from initiation of prophylactic medication and intensive monitoring of recurrence. AIMS: To assess the current evidence on patient-related, microbial, surgical and histopathological risk factors for ePOR in patients with CD after ileocolic (re-)resection. METHODS: Multiple online databases (Embase, MEDLINE, Web of Science and Cochrane Library) were searched up to March 2024. Studies with reported associations of patient-related, microbial, surgical and/or histopathological factors for ePOR (i.e., Rutgeerts' score ≥i2 or modified Rutgeerts' score ≥i2a) were included. The risk of bias was assessed with the Newcastle-Ottawa Scale for observational cohort studies and case-control studies. RESULTS: In total, 47 studies were included (four RCTs, 29 cohort studies, 12 case-control studies, one cross-sectional study and one individual participant data meta-analysis) including 6006 patients (median sample size 87 patients [interquartile range 46-170]). Risk of bias assessment revealed a poor quality in 41% of the studies. An association was reported in multiple studies of ePOR with active smoking at and post-surgery, male sex and prior bowel resection. A heterogeneous association with ePOR was reported for other risk factors included in the current guidelines (penetrating disease, perianal disease, younger age, extensive small bowel disease and presence of granulomas in the resection specimen or myenteric plexitis in the resection margin), and other patient-related, microbial, surgical and histopathological factors. CONCLUSION: Risk factors for ePOR in international guidelines are not consistently reported as risk factors in current literature except for active smoking and prior bowel resection. To develop evidence-based, personalised strategies, large prospective studies are warranted to identify risk factors for ePOR. Validation studies of promising (bio)markers are also required.

Evaluation of walking activity and gait to identify physical and mental fatigue in neurodegenerative and immune disorders: preliminary insights from the IDEA-FAST feasibility study.

BACKGROUND: Many individuals with neurodegenerative (NDD) and immune-mediated inflammatory disorders (IMID) experience debilitating fatigue. Currently, assessments of fatigue rely on patient reported outcomes (PROs), which are subjective and prone to recall biases. Wearable devices, however, provide objective and reliable estimates of gait, an essential component of health, and may present objective evidence of fatigue. This study explored the relationships between gait characteristics derived from an inertial measurement unit (IMU) and patient-reported fatigue in the IDEA-FAST feasibility study. METHODS: Participants with IMIDs and NDDs (Parkinson's disease (PD), Huntington's disease (HD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjogren's syndrome (PSS), and inflammatory bowel disease (IBD)) wore a lower-back IMU continuously for up to 10 days at home. Concurrently, participants completed PROs (physical fatigue (PF) and mental fatigue (MF)) up to four times a day. Macro (volume, variability, pattern, and acceleration vector magnitude) and micro (pace, rhythm, variability, asymmetry, and postural control) gait characteristics were extracted from the accelerometer data. The associations of these measures with the PROs were evaluated using a generalised linear mixed-effects model (GLMM) and binary classification with machine learning. RESULTS: Data were recorded from 72 participants: PD = 13, HD = 9, RA = 12, SLE = 9, PSS = 14, IBD = 15. For the GLMM, the variability of the non-walking bouts length (in seconds) with PF returned the highest conditional R2, 0.165, and with MF the highest marginal R2, 0.0018. For the machine learning classifiers, the highest accuracy of the current analysis was returned by the micro gait characteristics with an intrasubject cross validation method and MF as 56.90% (precision = 43.9%, recall = 51.4%). Overall, the acceleration vector magnitude, bout length variation, postural control, and gait rhythm were the most interesting characteristics for future analysis. CONCLUSIONS: Counterintuitively, the outcomes indicate that there is a weak relationship between typical gait measures and abnormal fatigue. However, factors such as the COVID-19 pandemic may have impacted gait behaviours. Therefore, further investigations with a larger cohort are required to fully understand the relationship between gait and abnormal fatigue.

Variation Between Hospitals in Outcomes and Costs of IBD Care: Results From the IBD Value Study.

BACKGROUND: Data on variation in outcomes and costs of the treatment of inflammatory bowel disease (IBD) can be used to identify areas for cost and quality improvement. It can also help healthcare providers learn from each other and strive for equity in care. We aimed to assess the variation in outcomes and costs of IBD care between hospitals. METHODS: We conducted a 12-month cohort study in 8 hospitals in the Netherlands. Patients with IBD who were treated with biologics and new small molecules were included. The percentage of variation in outcomes (following the International Consortium for Health Outcomes Measurement standard set) and costs attributable to the treating hospital were analyzed with intraclass correlation coefficients (ICCs) from case mix-adjusted (generalized) linear mixed models. RESULTS: We included 1010 patients (median age 45 years, 55% female). Clinicians reported high remission rates (83%), while patient-reported rates were lower (40%). During the 12-month follow-up, 5.2% of patients used prednisolone for more than 3 months. Hospital costs (outpatient, inpatient, and medication costs) were substantial (median: €8323 per 6 months), mainly attributed to advanced therapies (€6611). Most of the variation in outcomes and costs among patients could not be attributed to the treating hospitals, with ICCs typically between 0% and 2%. Instead, patient-level characteristics, often with ICCs above 50%, accounted for these variations. CONCLUSIONS: Variation in outcomes and costs cannot be used to differentiate between hospitals for quality of care. Future quality improvement initiatives should look at differences in structure and process measures of care and implement patient-level interventions to improve quality of IBD care. TRIAL REGISTRATION NUMBER: NL8276.

Variation in outcomes and costs cannot be used to differentiate between hospitals for quality of inflammatory bowel disease care. Future quality improvement initiatives should look at differences in structure and process measures and implement patient-level interventions to improve quality of inflammatory bowel disease care.

A Prediction Model for Successful Increase of Adalimumab Dose Intervals in Patients with Crohn's Disease: Secondary Analysis of the Pragmatic Open-Label Randomised Controlled Non-inferiority LADI Trial.

BACKGROUND: In the pragmatic open-label randomised controlled non-inferiority LADI trial we showed that increasing adalimumab (ADA) dose intervals was non-inferior to conventional dosing for persistent flares in patients with Crohn's disease (CD) in clinical and biochemical remission. AIMS: To develop a prediction model to identify patients who can successfully increase their ADA dose interval based on secondary analysis of trial data. METHODS: Patients in the intervention group of the LADI trial increased ADA intervals to 3 and then to 4 weeks. The dose interval increase was defined as successful when patients had no persistent flare (> 8 weeks), no intervention-related severe adverse events, no rescue medication use during the study, and were on an increased dose interval while in clinical and biochemical remission at week 48. Prediction models were based on logistic regression with relaxed LASSO. Models were internally validated using bootstrap optimism correction. RESULTS: We included 109 patients, of which 60.6% successfully increased their dose interval. Patients that were active smokers (odds ratio [OR] 0.90), had previous CD-related intra-abdominal surgeries (OR 0.85), proximal small bowel disease (OR 0.92), an increased Harvey-Bradshaw Index (OR 0.99) or increased faecal calprotectin (OR 0.997) were less likely to successfully increase their dose interval. The model had fair discriminative ability (AUC = 0.63) and net benefit analysis showed that the model could be used to select patients who could increase their dose interval. CONCLUSION: The final prediction model seems promising to select patients who could successfully increase their ADA dose interval. The model should be validated externally before it may be applied in clinical practice. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, number NCT03172377.

Interobserver agreement of current and new proposed endoscopic scores for postoperative recurrence in Crohn's disease.

BACKGROUND AND AIMS: The modified Rutgeerts' score (mRS) is widely used for the assessment of endoscopic postoperative recurrence (ePOR) in Crohn's disease (CD) after ileocolic resection to guide therapeutic decisions. To improve the validity and prognostic value of this endoscopic assessment, two new scores have been proposed. This study assessed the interobserver agreement of the current (mRS) and new endoscopic scores for ePOR in CD. METHODS: Sixteen Dutch academic and non-academic IBD specialists assessed endoscopic videos (n=71) of postoperative CD patients (n=66) retrieved from nine Dutch centers. Each video was assessed for the degree of inflammation by four gastroenterologists using the mRS and the new proposed endoscopic score: REMIND score (separate score of anastomosis and neoterminal ileum) and updated Rutgeerts score (assessment of lesions at the anastomotic line, ileal inlet, ileal body and neoterminal ileum). In addition, lesions at the ileal body, ileal inlet, neoterminal ileum, colonic and/or ileal blind loop were separately assessed. Interobserver agreement was assessed using Fleiss' weighted kappa. RESULTS: Fleiss' weighted kappa for the mRS was 0.67 (95% confidence interval [CI] 0.59-0.74). The weighted kappa for the REMIND score was 0.73 (95% CI 0.65-0.80) for lesions in the neoterminal ileum and 0.46 (95% CI 0.35-0.58) for anastomotic lesions. The weighted kappa for the updated Rutgeerts' score was 0.69 (95% CI 0.62-0.77). The weighted kappa for lesions in the ileal body, ileal inlet, neoterminal ileum, colonic and ileal blind loop was 0.61 (95% CI 0.49-0.73), 0.63 (95% CI 0.54-0.72), 0.61 (95% CI 0.49-0.74), 0.83 (95% CI 0.62-1.00) and 0.68 (95% CI 0.46-0.89). CONCLUSION: The interobserver agreement of the mRS is substantial. Similarly, the interobserver agreement is substantial for the updated Rutgeerts' score. According to the REMIND score, the interobserver agreement was substantial for lesions in the neoterminal ileum, whereas only moderate for anastomotic lesions. Since therapeutic decisions in clinical practice are based on these assessments and these scores are used as outcome measure in clinical studies, further improvement of the interobserver agreement is essential.

Fatigue-Related Changes of Daily Function: Most Promising Measures for the Digital Age.

Background: Fatigue is a prominent symptom in many diseases and is strongly associated with impaired daily function. The measurement of daily function is currently almost always done with questionnaires, which are subjective and imprecise. With the recent advances of digital wearable technologies, novel approaches to evaluate daily function quantitatively and objectively in real-life conditions are increasingly possible. This also creates new possibilities to measure fatigue-related changes of daily function using such technologies. Summary: This review examines which digitally assessable parameters in immune-mediated inflammatory and neurodegenerative diseases may have the greatest potential to reflect fatigue-related changes of daily function. Key Messages: Results of a standardized analysis of the literature reporting about perception-, capacity-, and performance-evaluating assessment tools indicate that changes of the following parameters: physical activity, independence of daily living, social participation, working life, mental status, cognitive and aerobic capacity, and supervised and unsupervised mobility performance have the highest potential to reflect fatigue-related changes of daily function. These parameters thus hold the greatest potential for quantitatively measuring fatigue in representative diseases in real-life conditions, e.g., with digital wearable technologies. Furthermore, to the best of our knowledge, this is a new approach to analysing evidence for the design of performance-based digital assessment protocols in human research, which may stimulate further systematic research in this area.

Pregnancy Outcomes in the Ozanimod Clinical Development Program in Patients With Ulcerative Colitis, Crohn's Disease, and Relapsing Multiple Sclerosis.

This study evaluated pregnancy outcomes in patients with ulcerative colitis, Crohn's disease, or multiple sclerosis and in healthy volunteers treated with ozanimod. There was no increased incidence of fetal abnormalities or adverse pregnancy outcomes with ozanimod exposure during early pregnancy.

Prognostic Value of the Modified Rutgeerts Score for Long-Term Outcomes After Primary Ileocecal Resection in Crohn's Disease.

INTRODUCTION: The prognostic value of the modified Rutgeerts score (mRS) in patients with Crohn's disease (CD) needs to be further elucidated. This study assessed the prognostic value of the mRS for long-term outcomes after primary ileocecal resection in patients with CD. METHODS: Patients with CD after primary ileocecal resection with an available mRS at first postoperative ileocolonoscopy (index mRS) were retrospectively included. The primary outcome was surgical recurrence. Secondary outcomes were clinical recurrence and progression to severe endoscopic recurrence (≥i3). Cox proportional hazard models were used to assess the association between index mRS and outcomes. RESULTS: Six hundred fifty-two patients were included (mean follow-up: 6.4 years, SD: 4.6). Surgical recurrence rates were 7.7%, 5.3%, 12.9%, 19.1%, 28.8%, 47.8% for index mRS i0, i1, i2a, i2b, i3, and i4, respectively. Clinical recurrence occurred in 42.2% (i0), 53.7% (i1), 58.5% (i2a), 80.2% (i2b), 79.4% (i3), and 95.3% (i4) of patients. Progression to severe endoscopic recurrence occurred in 21.1% (i0), 33.9% (i1), 26.8% (i2a), and 33.3% (i2b) of patients. An index mRS of i2b (adjusted hazard ratio [aHR] 3.0; 1.5-5.6), i3 (aHR 4.0; 2.0-7.9) and i4 (aHR 8.0; 4.0-16.0) were associated with surgical recurrence. An index mRS of i1 (aHR 1.7; 1.2-2.4), i2a (aHR 1.7; 1.2-2.4), i2b (aHR 4.4; 3.2-6.0), i3 (aHR 3.6; 2.5-5.2), and i4 (aHR 7.3; 4.8-10.9) were associated with clinical recurrence. An index mRS of i1 (aHR 2.0; 1.1-3.7) or i2b (aHR 2.5; 1.4-4.6) was associated with progression to severe endoscopic recurrence. DISCUSSION: The increasing mRS corresponds closely with the risk of surgical and clinical recurrence. An index mRS ≥ i2b is associated with surgical recurrence, an index mRS ≥ i1 is associated with clinical recurrence, and i1 or i2b with progression to severe endoscopic recurrence. These results support tight monitoring of disease activity and treatment optimization in patients with ileal lesions and a more conservative management in patients with anastomotic lesions.

Identification of Fatigue and Sleepiness in Immune and Neurodegenerative Disorders from Measures of Real-World Gait Variability.

Current assessments of fatigue and sleepiness rely on patient reported outcomes (PROs), which are subjective and prone to recall bias. The current study investigated the use of gait variability in the "real world" to identify patient fatigue and daytime sleepiness. Inertial measurement units were worn on the lower backs of 159 participants (117 with six different immune and neurodegenerative disorders and 42 healthy controls) for up to 20 days, whom completed regular PROs. To address walking bouts that were short and sparse, four feature groups were considered: sequence-independent variability (SIV), sequence-dependant variability (SDV), padded SDV (PSDV), and typical gait variability (TGV) measures. These gait variability measures were extracted from step, stride, stance, and swing time, step length, and step velocity. These different approaches were compared using correlations and four machine learning classifiers to separate low/high fatigue and sleepiness.Most balanced accuracies were above 50%, the highest was 57.04% from TGV measures. The strongest correlation was 0.262 from an SDV feature against sleepiness. Overall, TGV measures had lower correlations and classification accuracies.Identifying fatigue or sleepiness from gait variability is extremely complex and requires more investigation with a larger data set, but these measures have shown performances that could contribute to a larger feature set.Clinical relevance- Gait variability has been repeatedly used to assess fatigue in the lab. The current study, however, explores gait variability for fatigue and daytime sleepiness in real-world scenarios with multiple gait-impacted disorders.

A Core Outcome Set for inflammatory bowel diseases: development and recommendations for implementation in clinical practice through an international multi-stakeholder consensus process.

BACKGROUND AND AIMS: Standardising health outcome measurements supports delivery of care, enables data-driven learning systems, and secondary data use for research. As part of the Health Outcomes Observatory initiative and building on existing knowledge, a core outcome set (COS) for inflammatory bowel diseases (IBD) was defined through an international modified Delphi method. METHODS: Stakeholders rated 90 variables on a 9-point importance scale twice, allowing score modification based on feedback displayed per stakeholder group. Two consecutive consensus meetings were held to discuss results and formulate recommendations for measurement in clinical practice. Variables scoring 7 or higher by ≥80% of the participants, or based on consensus meeting agreement, were included in the final set. RESULTS: In total, 136 stakeholders (45 IBD patients (advocates), 74 healthcare professionals/researchers, 13 industry representatives and 4 regulators), from 20 different countries participated. The final set includes 18 case-mix variables, 3 biomarkers (haemoglobin to detect anaemia, C-reactive protein and faecal calprotectin to detect inflammation) for completeness and 28 outcomes (including 16 patient-reported outcomes (PROs) and 1 patient-reported experience). The PRO-2 and IBD-Control questionnaires were recommended to collect disease-specific PROs at every contact with an IBD practitioner, and the Subjective Health Experience model questionnaire, PROMIS Global Health and Self-Efficacy short form to collect generic PROs annually. CONCLUSIONS: A COS for IBD, including a recommendation for use in clinical practice, was defined. Implementation of this set will start in Vienna, Berlin, Barcelona, Leuven and Rotterdam, empowering patients to better manage their care. Additional centres will follow worldwide.

Validation of the pharmacokinetic model for anti- TNFα clearance in infants exposed to anti- TNFα during pregnancy.

BACKGROUND AND AIMS: ECCO guideline recommend postponing live attenuated vaccines in infants exposed to anti-Tumor Necrosis Factor alpha (anti-TNFα) in utero until drug clearance. The aim was to validate the predictive performance of the anti-TNFα clearance model. METHODS: Newborns and anti-TNFα concentrations from the prospective PETIT cohort were included. The anti-TNFα clearance model was used to predict all measured concentrations in the PETIT cohort, based on the measured cord blood concentration and the mean population clearance described in the model. Bayesian maximum a posteriori optimization was used to estimate the value of drug monitoring. Predictive capability and drug monitoring were assessed through Mean Absolute Error (MAE), Root mean Squared Prediction Error and Limits of Agreement according to Bland and Altman. RESULTS: Observed drug concentrations after birth were within the 80% prediction interval in 94% of adalimumab samples and 93% of infliximab samples. The anti-TNFα clearance model accurately predicted the concentration at six months after birth with an MAE of 0.03 (SD 0.03) µg/mL for adalimumab and 0.11 (SD 0.18) µg/mL for infliximab based on cord blood concentrations. Addition of an additional sample between 1 and 4 months after birth improved the predictive accuracy for infliximab (MAE 0.05 (SD 0.09)) but not for adalimumab. Guidance for use in clinical practice was formulated. CONCLUSIONS: The validity of the anti-TNFα clearance model is high, and hence can be used to guide clinicians regarding timing of live vaccines in infants exposed to adalimumab or infliximab in utero.

Impact of timing of primary ileocecal resection on prognosis in patients with Crohn's disease.

BACKGROUND: The advantage of early ileocecal resection after Crohn's disease diagnosis is a matter of debate. This study aims to assess the timing of ileocecal resection on prognosis, after correction for possible confounders. METHODS: Patients with Crohn's disease with primary ileocecal resection between 2000 and 2019 were included in a retrospective multicentre cohort. The primary endpoint was endoscopic recurrence (Rutgeerts score ≥i2b) within 18 months. Secondary endpoints were escalation of inflammatory bowel disease medication within 18 months and re-resection during follow-up. The association between timing of ileocecal resection and these endpoints was investigated using multivariable proportional hazard models, corrected for covariates including Montreal classification, postoperative prophylaxis, smoking, indication for surgery, medication before ileocecal resection, perianal fistulas, surgical approach, histology, length of resected segment and calendar year. RESULTS: In 822 patients ileocecal resection was performed after a median of 3.1 years (i.q.r. 0.7-8.0) after Crohn's disease diagnosis. The lowest incidence of endoscopic recurrence, escalation of inflammatory bowel disease medication and re-resection was observed for patients undergoing ileocecal resection shortly after diagnosis (0-1 months). After correction for covariates, patients with ileocecal resection at 0, 4 and 12 months after diagnosis had a cumulative incidence of 35 per cent, 48 per cent and 39 per cent for endoscopic recurrence, 20 per cent, 29 per cent and 28 per cent for escalation of inflammatory bowel disease medication and 20 per cent, 30 per cent and 34 per cent for re-resection, respectively. In the multivariable model ileocolonic disease (HR 1.39 (95 per cent c.i. 1.05 to 1.86)), microscopic inflammation of proximal and distal resection margins (HR 2.20 (95 per cent c.i. 1.21 to 3.87)) and postoperative prophylactic biological and immunomodulator (HR 0.16 (95 per cent c.i. 0.05 to 0.43)) were associated with endoscopic recurrence. CONCLUSION: The timing of ileocecal resection was not associated with a change of disease course; in the multivariable model, the postoperative recurrence was not affected by timing of ileocecal resection.

SARS-CoV-2 breakthrough infections after COVID-19 vaccination in patients with inflammatory bowel disease: a systematic review and meta-analysis.

Background: Patients with inflammatory bowel disease (IBD) have an attenuated serologic response to COVID-19 vaccination. It is unclear whether an impaired immune response in vaccinated IBD patients impacts the susceptibility to SARS-CoV-2 infection and occurrence of severe COVID-19. Objectives: To evaluate SARS-CoV-2 breakthrough infection rates and the disease course of COVID-19 in vaccinated IBD patients. Design: A systematic literature search and meta-analysis was performed. Data sources and methods: The search was performed in Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and CINAHIL. The articles were independently screened and selected by two reviewers. A random-effects model was used to calculate the pooled relative risk for breakthrough infections in vaccinated IBD patients and controls. Results: A total of 16 studies were included, with study periods ranging from January 2020 to October 2021 and follow-up time from 3 weeks to 6 months. The breakthrough infection rates range from 0 to 37.4% in vaccinated IBD patients. The disease course of COVID-19 was generally mild, with low hospitalization and mortality rates (0-8.7% and 0-4.3%, respectively). Vaccinated IBD patients had a significantly lower relative risk of breakthrough infection rate compared to unvaccinated controls (risk ratio: 0.07, 95% CI: 0.03-0.18). No difference was observed between IBD patients and non-IBD controls, and between partially and fully vaccinated IBD patients. The impact of immunosuppressive therapy on breakthrough infection rates differs between studies. Most studies showed no impact from immunosuppressive treatment, anti-tumour necrosis factor alpha or corticosteroids and other biologics; one study reported higher rates for patients treated with infliximab versus vedolizumab. Conclusion: Vaccination is effective to prevent COVID-19 infections in patients with IBD. Breakthrough infections do occur, but the disease course is generally mild. Available data seem to suggest a declining trend of breakthrough infections during calendar time. Registration: The protocol was published in the PROSPERO database (CRD42021292853).

Cost-Effectiveness Analysis of Increased Adalimumab Dose Intervals in Crohn's Disease Patients in Stable Remission: The Randomized Controlled LADI Trial.

BACKGROUND AND AIMS: We aimed to assess cost-effectiveness of increasing adalimumab dose intervals compared to the conventional dosing interval in patients with Crohn's disease [CD] in stable clinical and biochemical remission. DESIGN: We conducted a pragmatic, open-label, randomized controlled non-inferiority trial, comparing increased adalimumab intervals with the 2-weekly interval in adult CD patients in clinical remission. Quality of life was measured with the EQ-5D-5L. Costs were measured from a societal perspective. Results are shown as differences and incremental net monetary benefit [iNMB] at relevant willingness to accept [WTA] levels. RESULTS: We randomized 174 patients to the intervention [n = 113] and control [n = 61] groups. No difference was found in utility (difference: -0.017, 95% confidence interval [-0.044; 0.004]) and total costs (-€943, [-€2226; €1367]) over the 48-week study period between the two groups. Medication costs per patient were lower (-€2545, [-€2780; -€2192]) in the intervention group, but non-medication healthcare (+€474, [+€149; +€952]) and patient costs (+€365 [+€92; €1058]) were higher. Cost-utility analysis showed that the iNMB was €594 [-€2099; €2050], €69 [-€2908; €1965] and -€455 [-€4,096; €1984] at WTA levels of €20 000, €50 000 and €80 000, respectively. Increasing adalimumab dose intervals was more likely to be cost-effective at WTA levels below €53 960 per quality-adjusted life year. Above €53 960 continuing the conventional dose interval was more likely to be cost-effective. CONCLUSION: When the loss of a quality-adjusted life year is valued at less than €53 960, increasing the adalimumab dose interval is a cost-effective strategy in CD patients in stable clinical and biochemical remission. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, number NCT03172377.

Dutch normative data of the sexual distress scale and the body image scale.

PURPOSE: Sexual health is an important contributing factor for health-related quality of life, but research in this domain is scarce. Moreover, normative data are needed to interpret patient-reported outcome measures on sexual health. The aim of this study was to collect and describe normative scores of the Female Sexual Distress Scale (FSDS) and the Body Image Scale (BIS) from the Dutch population and assess the effect of important demographic and clinical variables on the outcome. As the FSDS is also validated in men, we refer to it as SDS. METHOD: Dutch respondents completed the SDS and BIS between May and August 2022. Sexual distress was defined as a SDS score > 15. Descriptive statistics were calculated to present normative data per age group per gender after post-stratification weighting was applied. Multiple logistic and linear regression analyses were conducted to assess the effect of age, gender, education, relationship status, history of cancer and (psychological) comorbidities on SDS and BIS. RESULTS: For the SDS 768 respondents were included with a weighted mean score of 14.41 (SD 10.98). Being female (OR 1.77, 95% CI [1.32; 2.39]), having a low educational level (OR 2.02, CI [1.37; 2.39]) and psychological comorbidities (OR: 4.86, 95% CI [2.17; 10.88]) were associated with sexual distress. For the BIS, 696 respondents were included. Female gender (ß: 2.63, 95% CI [2.13; 3.13]), psychological comorbidities (ß: 2.45, 95% CI [1.43; 3.47]), higher age (ß: -0.07, 95% CI [-0.09; -0.05]), and a high educational level (ß:-1.21, CI: -1.79 to -0.64) were associated with the non-disease related questions of the Body Image Scale. CONCLUSION: This study provides age- and gender-dependent normative values for the SDS and the non-disease related questions of the BIS. Sexual distress and body image are influenced by gender, education level, relationship status and psychological comorbidities. Moreover, age is positively associated with Body Image.

Cardiovascular risk profiles in patients with inflammatory bowel disease differ from matched controls from the general population.

AIMS: Inflammatory bowel disease (IBD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). We compared cardiovascular disease (CVD) risk factors and 10-year risk in IBD patients to the general population. METHODS AND RESULTS: In this cross-sectional study, consecutive IBD patients ≥45 years were included. History of ASCVD and CVD risk factors (smoking, hypertension, overweight, hypercholesterolaemia, diabetes, and metabolic syndrome) were assessed. The Systematic COronary Risk Evaluation (SCORE2) algorithm was used to estimate 10-year CVD risk. One to four age/sex-matched controls were derived from the prospective population-based Rotterdam Study cohort. In total, 235 IBD patients were included {56% women, median age 59 years [interquartile range (IQR) 51-66]} and matched to 829 controls [56% women, median age 61 years (IQR 56-67)]. Inflammatory bowel disease patients experienced ASCVD events more often compared with matched controls [odds ratio (OR) 2.01, 95% confidence interval (CI) 1.23-3.27], specifically heart failure (OR 2.02, 95% CI 1.02-4.01) and coronary heart disease (OR 2.01, 95% CI 1.7-3.13). Inflammatory bowel disease patients showed lower odds of overweight (OR 0.48, 95% CI 0.35-0.66) and hypercholesterolaemia (OR 0.45, 95% CI 0.31-0.65) and higher odds of hypertension (OR 1.67, 95% CI 1.19-2.32), as well as higher waist circumference (+4 cm, P = 0.006) and triglyceride levels (+0.6 mmol/L, P < 0.001) as compared with controls. Mean 10-year CVD risk was 4.0% [standard deviation (SD) ±2.6] in 135 IBD patients vs. 6.0% (SD ±1.6) in 506 controls. CONCLUSION: The increased CVD risk in IBD is discrepant with the 10-year CVD risk estimate. Systematic COronary Risk Evaluation may underestimate CVD risk in IBD patients due to differing CVD risk profiles compared with the general population, including a lower prevalence of hypercholesterolaemia and overweight and a higher prevalence of hypertension, abdominal obesity, and hypertriglyceridaemia.

The unfavourable CVD risk profiles in IBD patients compared with the general population are discrepant with the calculated 10-year CVD risk with the SCORE2 algorithm. Cardiovascular disease risk profiles in IBD patients differ from age/sex-matched controls, including a lower prevalence of hypercholesterolaemia and overweight and a higher prevalence of CVD history, hypertension, abdominal obesity, and hypertriglyceridaemia.Systematic COronary Risk Evaluation was comparable between IBD patients and controls; however, the proportion of patients with 10-year CVD risk above the treatment threshold was lower among IBD patients.

Digital Outcome Measurement to Improve Care for Patients With Immune-Mediated Inflammatory Diseases: Protocol for the IMID Registry.

BACKGROUND: Despite enormous clinical improvements, due to better management strategies and the availability of biologicals, immune-mediated inflammatory diseases (IMIDs) still have a significant impact on patients' lives. To further reduce disease burden, provider- as well as patient-reported outcomes (PROs) should be taken into account during treatment and follow-up. Web-based collection of these outcomes generates valuable repeated measurements, which could be used (1) in daily clinical practice for patient-centered care, including shared decision-making; (2) for research purposes; and (3) as an essential step toward the implementation of value-based health care (VBHC). Our ultimate goal is that our health care delivery system is completely aligned with the principles of VBHC. For aforementioned reasons, we implemented the IMID registry. OBJECTIVE: The IMID registry is a digital system for routine outcome measurement that mainly includes PROs to improve care for patients with IMIDs. METHODS: The IMID registry is a longitudinal observational prospective cohort study within the departments of rheumatology, gastroenterology, dermatology, immunology, clinical pharmacy, and outpatient pharmacy of the Erasmus MC, the Netherlands. Patients with the following diseases are eligible for inclusion: inflammatory arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, uveitis, Behçet disease, sarcoidosis, and systemic vasculitis. Generic and disease-specific (patient-reported) outcomes, including adherence to medication, side effects, quality of life, work productivity, disease damage, and activity, are collected from patients and providers at fixed intervals before and during outpatient clinic visits. Data are collected and visualized through a data capture system, which is linked directly to the patients' electronic health record, which not only facilitates a more holistic care approach, but also helps with shared decision-making. RESULTS: The IMID registry is an ongoing cohort with no end date. Inclusion started in April 2018. From start until September 2022, a total of 1417 patients have been included from the participating departments. The mean age at inclusion was 46 (SD 16) years, and 56% of the patient population is female. The average percentage of filled out questionnaires at baseline is 84%, which drops to 72% after 1 year of follow-up. This decline may be due to the fact that the outcomes are not always discussed during the outpatient clinic visit or because the questionnaires were sometimes forgotten to set out. The registry is also used for research purposes and 92% of the patients with IMIDs gave informed consent to use their data for that. CONCLUSIONS: The IMID registry is a web-based digital system that collects provider- and PROs. The collected outcomes are used to improve care for the individual patient with an IMID and facilitate shared decision-making, and they are also used for research purposes. The measurement of these outcomes is an essential step toward the implementation of VBHC. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43230.

Increased versus conventional adalimumab dose interval for patients with Crohn's disease in stable remission (LADI): a pragmatic, open-label, non-inferiority, randomised controlled trial.

BACKGROUND: Despite its effectiveness in treating Crohn's disease, adalimumab is associated with an increased risk of infections and high health-care costs. We aimed to assess clinical outcomes of increased adalimumab dose intervals versus conventional dosing in patients with Crohn's disease in stable remission. METHODS: The LADI study was a pragmatic, open-label, multicentre, non-inferiority, parallel, randomised controlled trial, done in six academic hospitals and 14 general hospitals in the Netherlands. Adults (aged ≥18 years) diagnosed with luminal Crohn's disease (with or without concomitant perianal disease) were eligible when in steroid-free clinical and biochemical remission (defined as Harvey-Bradshaw Index [HBI] score <5, faecal calprotectin <150 µg/g, and C-reactive protein <10 mg/L) for at least 9 months on a stable dose of 40 mg subcutaneous adalimumab every 2 weeks. Patients were randomly assigned (2:1) to the intervention group or control group by the coordinating investigator using a secure web-based system with variable block randomisation (block sizes of 6, 9, and 12). Randomisation was stratified on concomitant use of thiopurines and methotrexate. Patients and health-care providers were not masked to group assignment. Patients allocated to the intervention group increased adalimumab dose intervals to 40 mg every 3 weeks at baseline and further to every 4 weeks if they remained in clinical and biochemical remission at week 24. Patients in the control group continued their 2-weekly dose interval. The primary outcome was the cumulative incidence of persistent flares at week 48 defined as the presence of at least two of the following criteria: HBI score of 5 or more, C-reactive protein 10 mg/L or more, and faecal calprotectin more than 250 µg/g for more than 8 weeks and a concurrent decrease in the adalimumab dose interval or start of escape medication. The non-inferiority margin was 15% on a risk difference scale. All analyses were done in the intention-to-treat and per-protocol populations. This trial was registered at ClinicalTrials.gov, NCT03172377, and is not recruiting. FINDINGS: Between May 3, 2017, and July 6, 2020, 174 patients were randomly assigned to the intervention group (n=113) or the control group (n=61). Four patients from the intervention group and one patient from the control group were excluded from the analysis for not meeting inclusion criteria. 85 (50%) of 169 participants were female and 84 (50%) were male. At week 48, the cumulative incidence of persistent flares in the intervention group (three [3%] of 109) was non-inferior compared with the control group (zero; pooled adjusted risk difference 1·86% [90% CI -0·35 to 4·07). Seven serious adverse events occurred, all in the intervention group, of which two (both patients with intestinal obstruction) were possibly related to the intervention. Per 100 person-years, 168·35 total adverse events, 59·99 infection-related adverse events, and 42·57 gastrointestinal adverse events occurred in the intervention group versus 134·67, 75·03, and 5·77 in the control group, respectively. INTERPRETATION: The individual benefit of increasing adalimumab dose intervals versus the risk of disease recurrence is a trade-off that should take patient preferences regarding medication and the risk of a flare into account. FUNDING: Netherlands Organisation for Health Research and Development.

Lipid Changes After Induction Therapy in Patients with Inflammatory Bowel Disease: Effect of Different Drug Classes and Inflammation.

BACKGROUND: Dyslipidemia may be an important modifiable risk factor contributing to the increased cardiovascular risk in inflammatory bowel disease (IBD). The lipid metabolism is subject to both systemic inflammation and drug therapy; however, it is unclear if this effect is drug-class dependent. Our aim was to assess lipid changes after IBD induction therapy and evaluate associated factors with a particular focus on drug class and disease activity. METHODS: In this prospective study, consecutive IBD patients starting systemic therapy (eg, corticosteroids, thiopurines, methotrexate, anti-TNF-α agents, vedolizumab, ustekinumab, and tofacitinib) were included. Primary outcomes were changes in total cholesterol, high density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides at week 10. RESULTS: One hundred ninety-eight IBD patients (107 women [54%], median age 36 years; interquartile range [IQR], 27-47) were included: 137 Crohn's disease (67%), 61 ulcerative colitis (29%), and 8 IBD-unclassified (4%). Median C-reactive protein and fecal calprotectin at baseline were 5.1 mg/L (IQR, 1.6-12.0) and 1040 ug/g (IQR, 383-1800), respectively. Relative increases in total cholesterol, HDL-c, and LDL-c were significant after prednisone (+26%, +31%, +12%) and tofacitinib therapy (+20%, +25%, +26%), respectively. Results remained after adjusting for concomitant corticosteroids, cholestyramine, and PSC diagnosis. Changes in clinical scores were inversely correlated with total cholesterol changes (R -186, P = .014), as was CRP with total cholesterol and LDL-c (R -0.292 and R -0.259, P < .001). No correlation was found with FCP. Lipid changes remained after adjusting for age and CRP. CONCLUSIONS: Prednisone and tofacitinib induction therapy significantly increase serum lipid levels, whereas no changes were observed in other drug classes. The observations seem drug-specific inasmuch as adjustment for systemic inflammation did not alter the results.

Prednisone and tofacitinib induction therapy increase lipid levels, whereas no changes are observed for immunomodulators and newer biologics. The observations seem drug-specific on top of control of inflammation. Studies on long-term consequences of IBD drug-induced lipid changes are required.