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.

Handling missing values in the analysis of between-hospital differences in ordinal and dichotomous outcomes: a simulation study.

Missing data are frequently encountered in registries that are used to compare performance across hospitals. The most appropriate method for handling missing data when analysing differences in outcomes between hospitals with a generalised linear mixed model is unclear. We aimed to compare methods for handling missing data when comparing hospitals on ordinal and dichotomous outcomes. We performed a simulation study using data from the Multicentre Randomised Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands (MR CLEAN) Registry, a prospective cohort study in 17 hospitals performing endovascular therapy for ischaemic stroke in the Netherlands. The investigated methods for handling missing data, both case-mix adjustment variables and outcomes, were complete case analysis, single imputation, multiple imputation, single imputation with deletion of imputed outcomes and multiple imputation with deletion of imputed outcomes. Data were generated as missing completely at random (MCAR), missing at random and missing not at random (MNAR) in three scenarios: (1) 10% missing data in case-mix and outcome; (2) 40% missing data in case-mix and outcome; and (3) 40% missing data in case-mix and outcome with varying degree of missing data among hospitals. Bias and reliability of the methods were compared on the mean squared error (MSE, a summary measure combining bias and reliability) relative to the hospital effect estimates from the complete reference data set. For both the ordinal outcome (ie, the modified Rankin Scale) and a common dichotomised version thereof, all methods of handling missing data were biased, likely due to shrinkage of the random effects. The MSE of all methods was on average lowest under MCAR and with fewer missing data, and highest with more missing data and under MNAR. The 'multiple imputation, then deletion' method had the lowest MSE for both outcomes under all simulated patterns of missing data. Thus, when estimating hospital effects on ordinal and dichotomous outcomes in the presence of missing data, the least biased and most reliable method to handle these missing data is 'multiple imputation, then deletion'.

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.

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.

Treatment of severe acute ulcerative colitis in SARS-CoV-2 infected patients: report of three cases and discussion of treatment options.

In the wake of the coronavirus disease 2019 (COVID-19) pandemic, it is unclear how asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients who present with acute severe ulcerative colitis (UC) can be treated effectively and safely. Standard treatment regimens consist of steroids, immunomodulatory drugs, and biological therapies, but therapeutic decision-making becomes challenging as there are uncertainties about how to deal with these drugs in patients with COVID-19 and active UC. Importantly, guidelines for this particular group of patients with UC are still lacking. To inform therapeutic decision-making, we describe three consecutive cases of patients with active UC and COVID-19 and discuss their treatments based on theoretical knowledge, currently available evidence and clinical observations. Three patients were identified through our national inflammatory bowel disease network [Initiative on Crohn's and Colitis (ICC)] for whom diagnosis of SARS-CoV-2-infection was established by reverse transcription-polymerase chain reaction (RT-PCR) testing in nasopharynx, stools, and/or biopsies. Acute severe UC was diagnosed by clinical parameters, endoscopy, and histopathology. Clinical guidelines for SARS-CoV-2-negative patients advocate the use of steroids, calcineurin inhibitors, or tumor necrosis factor alpha (TNF-α)-antagonists as induction therapy, and experiences from the current three cases show that steroids and TNF-α-antagonists could also be used in patients with COVID-19. This could potentially be followed by TNF-α-antagonists, vedolizumab, or ustekinumab as maintenance therapy in these patients. Future research is warranted to investigate if, and which, immunomodulatory drugs should be used for COVID-19 patients that present with active UC. To answer this question, it is of utmost importance that future cases of patients with UC and COVID-19 are documented carefully in international registries, such as the SECURE-IBD registry.