Simplified Machine Learning Models Can Accurately Identify High-Need High-Cost Patients With Inflammatory Bowel Disease.

INTRODUCTION: Hospitalization is the primary driver of inflammatory bowel disease (IBD)-related healthcare costs and morbidity. Traditional prediction models have poor performance at identifying patients at highest risk of unplanned healthcare utilization. Identification of patients who are high-need and high-cost (HNHC) could reduce unplanned healthcare utilization and healthcare costs. METHODS: We conducted a retrospective cohort study in adult patients hospitalized with IBD using the Nationwide Readmissions Database (model derivation in the 2013 Nationwide Readmission Database and validation in the 2017 Nationwide Readmission Database). We built 2 tree-based algorithms (decision tree classifier and decision tree using gradient boosting framework [XGBoost]) and compared traditional logistic regression to identify patients at risk for becoming HNHC (patients in the highest decile of total days spent in hospital in a calendar year). RESULTS: Of 47,402 adult patients hospitalized with IBD, we identified 4,717 HNHC patients. The decision tree classifier model (length of stay, Charlson Comorbidity Index, procedure, Frailty Risk Score, and age) had a mean area under the receiver operating characteristic curve (AUC) of 0.78 ± 0.01 in the derivation data set and 0.78 ± 0.02 in the validation data set. XGBoost (length of stay, procedure, chronic pain, drug abuse, and diabetic complication) had a mean AUC of 0.79 ± 0.01 and 0.75 ± 0.02 in the derivation and validation data sets, respectively, compared with AUC 0.55 ± 0.01 and 0.56 ± 0.01 with traditional logistic regression (peptic ulcer disease, paresthesia, admission for osteomyelitis, renal failure, and lymphoma) in derivation and validation data sets, respectively. DISCUSSION: In hospitalized patients with IBD, simplified tree-based machine learning algorithms using administrative claims data can accurately predict patients at risk of progressing to HNHC.

Trends in U.S. Health Care Spending on Inflammatory Bowel Diseases, 1996-2016.

BACKGROUND: Inflammatory bowel diseases (IBD) are rising in prevalence and are associated with high health care costs. We estimated trends in U.S. health care spending in patients with IBD between 1996 and 2016. METHODS: We used data on national health care spending developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project. We estimated corresponding U.S. age-specific prevalence of IBD from the Global Burden of Diseases Study. From these 2 sources, we estimated prevalence-adjusted, temporal trends in U.S. health care spending in patients with IBD, stratified by age groups (<20 years, 20-44 years, 45-64 years, ≥65 years) and by type of care (ambulatory, inpatient, emergency department [ED], pharmaceutical prescriptions, and nursing care), using joinpoint regression, expressed as an annual percentage change (APC) with 95% confidence intervals. RESULTS: Overall, annual U.S. health care spending on IBD increased from $6.4 billion (95% confidence interval, 5.7-7.4) in 1996 to $25.4 billion (95% confidence interval, 22.4-28.7) in 2016, corresponding to a per patient increase in annual spending from $5714 to $14,033. Substantial increases in per patient spending on IBD were observed in patients aged ≥45 years. Between 2011 and 2016, inpatient and ED care accounted for 55.8% of total spending and pharmaceuticals accounted for 19.9%, with variation across age groups (inpatient/ED vs pharmaceuticals: ages ≥65 years, 57.6% vs 11.2%; ages 45-64 years, 49.5% vs 26.9%; ages 20-44 years, 59.2% vs 23.6%). CONCLUSIONS: Even after adjusting for rising prevalence, U.S. health care spending on IBD continues to progressively increase, primarily in middle-aged and older adults, with unplanned health care utilization accounting for the majority of costs.

Digital Health Technologies for Remote Monitoring and Management of Inflammatory Bowel Disease: A Systematic Review.

INTRODUCTION: Digital health technologies may be useful tools in the management of chronic diseases. We performed a systematic review of digital health interventions in the management of patients with inflammatory bowel diseases (IBD) and evaluated its impact on (i) disease activity monitoring, (ii) treatment adherence, (iii) quality of life (QoL) measures, and/or (iv) health care utilization. METHODS: Through a systematic review of multiple databases through August 31, 2020, we identified randomized controlled trials in patients with IBD comparing digital health technologies vs standard of care (SoC) for clinical management and monitoring and reporting impact on IBD disease activity, treatment adherence, QoL, and/or health care utilization or cost-effectiveness. We performed critical qualitative synthesis of the evidence supporting digital health interventions in patients with IBD and rated certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Overall, we included 14 randomized controlled trials (median, 98 patients; range 34-909 patients; follow-up <12 months) that compared web-based interventions, mobile applications, and different telemedicine platforms with SoC (clinic-based encounters). Although overall disease activity and risk of relapse were comparable between digital health technologies and SoC (very low certainty of evidence), digital health interventions were associated with lower rate of health care utilization and health care costs (low certainty of evidence). Digital health interventions did not significantly improve patients' QoL and treatment adherence compared with SoC (very low certainty of evidence). Trials may have intrinsic selection bias due to nature of digital interventions. DISCUSSION: Digital health technologies may be effective in decreasing health care utilization and costs, though may not offer advantage in reducing risk of relapse, QoL, and improving treatment adherence in patients with IBD. These techniques may offer value-based care for population health management.

Recommendations for Standardizing Clinical Trial Design and Endoscopic Assessment in Postoperative Crohn's Disease.

BACKGROUND: The lack of standardized methods for clinical trial design and disease activity assessment has contributed to an absence of approved medical therapies for the prevention of postoperative Crohn's disease (CD). We developed recommendations for regulatory trial design for this indication and for endoscopic assessment of postoperative CD activity. METHODS: An international panel of 19 gastroenterologists was assembled. Modified Research and Development/University of California Los Angeles methodology was used to rate the appropriateness of 196 statements using a 9-point Likert scale in 2 rounds of voting. Results were reviewed and discussed between rounds. RESULTS: Inclusion of patients with a history of completely resected ileocolonic CD in regulatory clinical trials for the prevention of postoperative recurrence was appropriate. Given the absence of approved medical therapies, a placebo-controlled design with a primary end point of endoscopic remission at 52 weeks was appropriate for drug development for this indication; however, there was uncertainty regarding the appropriateness of a coprimary end point of symptomatic and endoscopic remission and the use of currently available patient-reported outcome measures. The modified Rutgeerts Score, endoscopic assessment of the anastomosis, and a minimum of 5cm of neoterminal ileum were also appropriate; although the appropriateness of other indices including the Simple Endoscopic Score for CD for endoscopic assessment of postoperative CD activity was uncertain. CONCLUSIONS: A framework for regulatory trial design for the prevention of postoperative CD recurrence and endoscopic assessment of disease activity has been developed. Research to empirically validate end points for these trials is needed.

A Microsimulation Model to Determine the Cost-Effectiveness of Treat-to-Target Strategies for Crohn's Disease.

INTRODUCTION: Cost-effectiveness of biomarker- vs endoscopy-based treat-to-target monitoring in Crohn's disease (CD) is unknown. METHODS: A microsimulation model for CD was built to simulate biomarker (fecal calprotectin) vs endoscopy-based monitoring in a treat-to-target fashion. Published literature in combination with patient-level data from phase 3 clinical trials and population estimates for therapeutic drug monitoring were used to generate transition probabilities, costs, and utilities. Tracker variables were used to modify downstream probabilities and outcomes based on previous exposures, response patterns, and disease-related complications or surgery history. The primary outcome was cost-effectiveness over a 5-year horizon at a willingness-to-pay threshold of $100,000/quality-adjusted life-year. Probabilistic sensitivity analyses in addition to multiple 1-, 2-, and 3-way microsimulation sensitivity analyses were performed. RESULTS: In the base-case model, the endoscopy-based monitoring strategy dominated the biomarker-based monitoring strategy over a 5-year horizon. Over shorter periods of observation, the biomarker-based monitoring strategy became progressively more cost-effective, with cost-effectiveness achieved for this strategy over a 1-year horizon. Therapeutic drug monitoring did not influence short-term cost-effectiveness of biomarker-based monitoring. Once in endoscopic remission, continued biomarker-based vs endoscopy-based monitoring was more cost-effective. A hybrid biomarker-endoscopy-based monitoring strategy dominated the endoscopy-based monitoring strategy over a 5-year horizon. The strongest determinants for cost-effectiveness were cost of colonoscopy and diagnostic performance of fecal calprotectin. DISCUSSION: The most cost-effective approach for treat-to-target monitoring in CD is up-front biomarker-based monitoring followed by endoscopy-based monitoring if not in endoscopic remission by 1 year and then returning to biomarker-based monitoring once in endoscopic remission.

Long-term Safety and Efficacy of the Anti-MAdCAM-1 Monoclonal Antibody Ontamalimab [SHP647] for the Treatment of Ulcerative Colitis: The Open-label Study TURANDOT II.

BACKGROUND AND AIMS: Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM-1, induced remission in patients with moderate-to-severe ulcerative colitis [UC] in the TURANDOT study. We aimed to assess long-term safety, tolerability, and efficacy of ontamalimab in TURANDOT II. METHODS: TURANDOT II was a phase 2, multicentre, open-label [OL] study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab (NCT01771809). Patients were randomised to 75 mg or 225 mg ontamalimab every 4 weeks for 72 weeks [OL1]. The dosage could be increased to 225 mg from Week 8 at the investigator's discretion. All patients then received 75 mg every 4 weeks for 72 weeks [OL2], followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events [AEs], serious AEs [SAEs], and AEs leading to withdrawal. Mucosal healing [MH; centrally read endoscopy] was assessed. RESULTS: Of 330 patients, 180 completed OL1; 94 escalated to 225 mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE [10.0%] was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis [0.9%]. One death and four cancers [all unrelated to ontamalimab] occurred. No PML [progressive multifocal leukoencephalopathy]/lymphoproliferative disorders occurred. Geometric mean high-sensitivity C-reactive protein [hsCRP] and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned to placebo in TURANDOT achieving MH increased from 8.8% [6/68] at baseline to 35.3% at Week 16 [24/68; non-responder imputation]. The corresponding increase in the ontamalimab group was from 23.3% [61/262] to 26.7% [70/262]. CONCLUSIONS: Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.

Long-term Safety and Efficacy of Etrasimod for Ulcerative Colitis: Results from the Open-label Extension of the OASIS Study.

BACKGROUND AND AIMS: Etrasimod is an oral, selective, sphingosine 1-phosphate receptor modulator. In a phase 2, randomised, double-blind, placebo-controlled trial in adults with moderately-to-severely active ulcerative colitis [OASIS], etrasimod 2 mg provided significant benefit versus placebo and was generally well tolerated. This open-label extension [OLE] evaluated safety and efficacy of etrasimod for up to 52 weeks. METHODS: In OASIS, 156 patients received etrasimod 1 mg, etrasimod 2 mg, or placebo, once daily for 12 weeks. After completing OASIS, patients could enrol in the OLE and receive etrasimod 2 mg for an additional 34-40 weeks. RESULTS: In all, 118 patients enrolled in the OLE; 112 patients received etrasimod 2 mg at any point and were evaluated for safety and efficacy. A total of 92 [82%] patients who received etrasimod 2 mg in the OLE completed the study. Treatment-emergent adverse events occurred in 60% [67/112] of patients receiving etrasimod 2 mg at any time, most commonly worsening ulcerative colitis and anaemia; 94% of adverse events were mild/moderate. At end of treatment, 64% of patients met the criteria for clinical response, 33% for clinical remission, and 43% for endoscopic improvement. Week 12 clinical response, clinical remission, or endoscopic improvement was maintained to end of treatment in 85%, 60%, or 69% of patients, respectively. Steroid-free clinical remission occurred in 22% of overall patients. CONCLUSIONS: In this long-term extension study, etrasimod 2 mg demonstrated a favourable safety profile. Most patients with clinical response, clinical remission, or endoscopic improvement at Week 12 maintained that status to end of treatment.

An expert consensus to standardise the assessment of histological disease activity in Crohn's disease clinical trials.

BACKGROUND: Targeting histological remission or response in Crohn's disease (CD) is not recommended in clinical practice guidelines or as an outcome in clinical trials due to uncertainties regarding index validity and prognostic relevance. AIMS: To conduct a modified RAND/University of California Los Angeles appropriateness process with the goal of producing a framework to standardise histological assessment of CD activity in clinical trials. METHODS: A total of 115 statements generated from literature review and expert opinion were rated on a scale of 1-9 by a panel of 11 histopathologists and 6 gastroenterologists. Statements were classified as inappropriate, uncertain or appropriate based upon the median panel rating and degree of disagreement. RESULTS: The panellists considered it important to measure histological activity in clinical trials to determine efficacy and that absence of neutrophilic inflammation is an appropriate histological target. They were uncertain whether the Global Histological Activity Score was an appropriate instrument for measuring histological activity. The Geboes Score and Robarts Histopathology Index were considered appropriate. Two biopsies from five segments should be biopsied, and the colon and the ileum should be analysed separately for all indices. Endoscopic mucosal appearance should guide biopsy procurement site with biopsies taken from the ulcer edge, or the most macroscopically inflamed area in the absence of ulcers. CONCLUSION: We evaluated the appropriateness of items for assessing histological disease activity in CD clinical trials. These items will be used to develop a novel histological index.

National Estimates of Financial Hardship From Medical Bills and Cost-related Medication Nonadherence in Patients With Inflammatory Bowel Diseases in the United States.

BACKGROUND: Inflammatory bowel diseases (IBDs) are associated with substantial health care needs. We estimated the national burden and patterns of financial toxicity and its association with unplanned health care utilization in adults with IBD in the United States. METHODS: Using the National Health Interview survey (2015), we identified individuals with self-reported IBD and assessed national estimates of financial toxicity across domains of financial hardship due to medical bills, cost-related medication nonadherence (CRN) and adoption of cost-reducing strategies, personal and health-related financial distress (worry about expenses), and health care affordability. We also evaluated the association of financial toxicity with emergency department (ED) utilization. RESULTS: Of the estimated 3.1 million adults with IBD in the United States, 23% reported financial hardships due to medical bills, 16% of patients reported CRN, and 31% reported cost-reducing behaviors. Approximately 62% of patients reported personal and/or health-related financial distress, and 10% of patients deemed health care unaffordable. Prevalence of financial toxicity was substantial even in participants with higher education, with private insurance, and belonging to middle/high-income families, highlighting underinsurance. Inflammatory bowel disease was associated with 1.6 to 2.6 times higher odds of financial toxicity across domains compared with patients without IBD. Presence of any marker of financial toxicity was associated with higher ED utilization. CONCLUSIONS: One in 4 adults with IBD experiences financial hardship due to medical bills, and 1 in 6 adults reports cost-related medication nonadherence. These financial determinates of health-especially underinsurance-have important implications in the context of value-based care.

Understanding Determinants of Patient Preferences Between Stool Tests and Colonoscopy for the Assessment of Disease Activity in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Evidence is now available in support of using fecal biomarkers to monitor disease activity in inflammatory bowel disease (IBD). Patient adherence is often cited as a barrier to implementation. We assessed patient determinants for using stool tests to monitor disease activity. METHODS: Prospective interview of IBD patients using an analytic hierarchy matrix survey built to understand preferences for choosing between stool testing or colonoscopy for monitoring disease activity, after considering different test criteria (accuracy, preparation, pain, complications). Theoretical thresholds of misclassification were posed to patients to see how they might consider shifting from colonoscopy to stool testing. RESULTS: A total of 100 patients (n = 51 CD, n = 46 male) were interviewed with median age and disease duration of 44 years (IQR 27-63) and 9 years (IQR 5-21), respectively. Stool-based testing was preferred over colonoscopy by 60% initially; however, a majority of participants changed their choice to colonoscopy after learning more about the diagnostic performance of currently available stool tests for disease monitoring (p < 0.001). Across all sub-groups, accuracy was ranked as the top criterion when choosing between stool-based testing and colonoscopy for disease activity assessments. Most patients were willing to choose stool-based testing over colonoscopy for disease monitoring if the stool test was wrong at most 1 in 20 times (5% misclassification rate). DISCUSSION: Accuracy is the most important criteria for IBD patients when choosing monitoring strategies, and a high degree of confidence is required of stool test results for patients to choose this strategy.

Microsimulation Model to Determine the Cost-Effectiveness of Treat-to-Target Strategies for Ulcerative Colitis.

BACKGROUND & AIMS: Little is known about the cost effectiveness of endoscopy or biomarker-based treat to target monitoring of patients with ulcerative colitis (UC). METHODS: We used a microsimulation model to identify the most cost effective treat to target monitoring strategy for patients with UC staring therapy with biologics or small molecule inhibitors. We assessed symptoms (rectal bleeding) alone, a combination of symptoms and a biomarker (fecal calprotectin), and endoscopy. Transition probabilities, costs, and quality-adjusted life year (QALY) estimates were derived from published estimates. The microsimulation model tracked an individual patient's disease course and treatment exposures to modify downstream treatment effectiveness, probabilities, and disease outcomes. The primary analysis included 100,000 individuals over 5 years with a willingness to pay threshold of $100,000/QALY. Probabilistic sensitivity analyses were performed with 500 samples and 250 trials, in addition to multiple 1-, 2-, and 3-way microsimulation sensitivity analyses. RESULTS: A total of 32 treatment sequencing algorithms were modeled alongside 3 disease monitoring strategies within a treat to target approach for UC. Combination symptom and biomarker-based monitoring resulted in the highest QALY estimate among all the treatment sequencing algorithms. However, monitoring disease activity with symptoms alone was the most cost-effective strategy in 86% of scenarios, followed by combination symptom and biomarker monitoring in 9%, and endoscopy monitoring in 5%. Results were sensitive to treatment costs, patient willingness to consider colectomy as a treatment option, and endoscopy costs. Endoscopy-based monitoring was favored when treatment costs were high and patients were unwilling to undergo colectomy. CONCLUSIONS: The combination symptom and biomarker-based monitoring resulted in the highest QALY estimate. However, symptom-based monitoring is the most cost-effective approach to implementing treat to target monitoring for patients with UC receiving biologics and small molecule inhibitors.

Prevalence and Effects of Food Insecurity and Social Support on Financial Toxicity in and Healthcare Use by Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: We estimated the prevalence of social determinants of health (SDH, food insecurity and social support) in adults with inflammatory bowel diseases (IBD) in the United States and evaluated associations with financial toxicity and healthcare use. METHODS: In the National Health Interview Survey 2015, we identified adults with IBD and estimated the prevalence of food insecurity and/or lack of social support. We evaluated associations with financial toxicity (financial hardship due to medical bills, personal and health-related financial distress, cost-related medication nonadherence, healthcare affordability) and emergency department use. RESULTS: Of estimated 3.1 million adults with IBD in the US, 42% or estimated 1,277,215 patients with IBD reported at least one negative SDH, with 12% reporting both food insecurity and lack of social support. On multivariable analysis adjusting for age, sex, race, family income and comorbidities, patients with food insecurity were significantly more likely to experience financial hardship due to medical bills (odds ratio [OR], 3.31; 95% CI, 1.48-7.39), financial distress (OR, 6.92; 95% CI, 2.28-21.0) and cost-related medication non-adherence (OR, 8.07; 95% CI, 3.16-20.6). Similarly, patients with inadequate social support were significantly more likely to experience financial hardship due to medical bills (OR, 2.98; 95% CI, 1.56-5.67), financial distress (OR, 3.05; 95% CI, 1.64-5.67) and cost-related medication non-adherence (OR, 2.71; 95% CI, 1.10-6.66). Food insecurity and/or lack of social support was not associated with increased risk of emergency department use. CONCLUSIONS: In an analysis of data from the National Health Interview Survey 2015, we found that 1 in 8 patients with IBD have food insecurity and lack social support, which is associated with higher financial toxicity. Patients with IBD should be assessed for SDH to tailor healthcare delivery and improve population health.

Burden and Outcomes of Fragmentation of Care in Hospitalized Patients With Inflammatory Bowel Diseases: A Nationally Representative Cohort.

BACKGROUND: Fragmentation of care (FoC) may adversely impact health care quality in patients with chronic diseases. We conducted a US nationally representative cohort study to evaluate the burden and outcomes of FoC in hospitalized patients with inflammatory bowel disease (IBD). METHODS: Using Nationwide Readmissions Database 2013, we created 2 cohorts of superutilizer patients with IBD with 2 hospitalizations (cohort 1: FoC, defined as readmission to nonindex hospital vs no FoC) or 3 hospitalizations (cohort 2: multiple episodes of fragmentation vs single episode of fragmentation vs no FoC) between January and June 2013, which were followed through December 2013. We evaluated burden, pattern, and outcomes of fragmentation (6-month risk of readmission, risk of surgery, and inpatient mortality). RESULTS: In cohort 1, of 6073 patients with IBD with 2 admissions within 6 months, 1394 (23%) experienced FoC. Fragmentation of care was associated with modestly higher risk of readmission within 6 months (31% vs 28%, P < 0.01; adjusted relative risk, 1.11 [1.01-1.21]), without differences in risk of surgery (2.8% vs 4.3%, P = 0.19) or in-hospital mortality (0.2% vs 0.5%, P = 0.22). In cohort 2, of 1717 patients with 3 hospitalizations within 6 months, the number of patients with multiple episodes of fragmentation was associated with higher risk of readmission compared with patients with single episode of fragmentation or no FoC (52% vs 49% vs 43%, P = 0.03). CONCLUSIONS: In a US cohort study, FoC is associated with a modestly higher risk of readmission, without higher risk of surgery or mortality in superutilizer patients with IBD. Future studies focusing on impact of outpatient care and postdischarge coordination are warranted in superutilizer patients.

Development of the symptoms and impacts questionnaire for Crohn's disease and ulcerative colitis.

BACKGROUND: Patient-reported outcome (PRO) measures historically used in inflammatory bowel disease have been considered inadequate to support future drug labelling claims by regulatory agencies. AIMS: To develop PRO tools for use in Crohn's disease (CD) and ulcerative colitis (UC) following guidance issued by the US FDA and the ISPOR (International Society for Pharmacoeconomics and Outcomes Research). METHODS: Concept elicitation and cognitive interviews were conducted in adult patients (≥18 years) across the United States and Canada. Semi-structured interview guides were used to collect data, and interview transcripts were coded and analysed. Concept elicitation results were considered alongside existing literature and clinical expert opinion to identify candidate PRO items. Cognitive interviews evaluated concept relevance, interpretability and structure, and facilitated instrument refinement. Concept elicitation participants, except those with an ostomy, underwent centrally read endoscopy to assess inflammatory status. RESULTS: In all, 54 participants (mean age: 46.2 years; 66.7% female) were included in the CD concept elicitation interviews. In total, 80 symptom concepts and 61 impact concepts were identified. After three waves of cognitive interviews, the 31-item Symptoms and Impacts Questionnaire for CD (SIQ-CD) was developed. In the UC concept elicitation phase, 53 participants were interviewed (mean age: 41.4 years; 49.1% female). In total, 79 symptoms concepts and 49 impact concepts were identified. Following two waves of cognitive interviews, the 29-item Symptoms and Impacts Questionnaire for UC (SIQ-UC) was developed. Both instruments include four symptom and six impact domains. CONCLUSIONS: We developed PROs to support CD and UC drug labelling claims. Psychometric validation studies to evaluate instrument reliability and responsiveness are ongoing.

Evaluation of optimal biopsy location for assessment of histological activity, transcriptomic and immunohistochemical analyses in patients with active Crohn's disease.

BACKGROUND: The appropriate location for biopsy procurement relative to an ulcer in active Crohn's disease is unknown. AIM: To explore the relationship between biopsy location, histological disease activity, proinflammatory gene expression and the presence of inflammatory cells. METHODS: Fifty-one patients with Crohn's disease and ulcers >0.5 cm diameter in the colon and/or ileum were prospectively enrolled at three centres. Biopsies were obtained from 0 mm, 7 to 8 mm and 21 to 24 mm from the edge of the largest ulcer. Histological activity was blindly assessed with the Global Histological Disease Activity Score, the Robarts Histopathology and Nancy Histological indices. Messenger ribonucleic acid (mRNA) levels for interleukins-6, -8 and -23 (p19 and p40 subunits), CD31 and S100A9 were measured using quantitative polymerase chain reaction. The number of CD3+, CD68+ and myeloperoxidase-positive cells was quantified by immunohistochemistry. Data were analysed using mixed models with location and segment as fixed effects and patients as random effect to account for correlation among segments within a patient. RESULTS: Histological disease activity scores (P < 0.0001), proinflammatory gene expression levels (P < 0.005) and numbers of myeloperoxidase-positive cells (P < 0.0001) were highest in biopsies from the ulcer edge in the colon and ileum, with decreasing gradients observed with distance from the edge (P < 0.05). No differences between colonic and ileal samples were detected for the parameters measured at any location. CONCLUSIONS: Biopsies from the ulcer edge in patients with Crohn's disease yielded the greatest histological disease activity and mRNA levels and had similar readouts in the colon and ileum. Research is needed to confirm this conclusion for other measures.

Market Access Analysis of Biologics and Small-Molecule Inhibitors for Inflammatory Bowel Disease Among US Health Insurance Policies.

BACKGROUND AND AIMS: Treatment pathways for ulcerative colitis (UC) and Crohn's disease (CD) are shifting to a more individualized, risk-stratified approach. The perception is that insurance policies may not have implemented this paradigm shift, particularly regarding access to newer agents. We evaluated patient access to advanced therapies by analyzing policy information from the Managed Markets Insight and Technology database. METHODS: Coverage status as of December 2018 for all US lives was queried for adalimumab, infliximab, infliximab-dyyb, tofacitinib, ustekinumab, and vedolizumab by indication (UC and/or CD) and medical or pharmacy coverage benefit. Coverage status was classified by the number of biologic steps before access to specified drug as "No Biologic," "1 Prior Biologic," "2+ Prior Biologics," "Not Covered." Unknown lives were excluded from the analyses. RESULTS: Coverage analysis was available for approximately 302 million lives under each medical and pharmacy benefit. Our analysis indicates that approximately half of covered lives had access to all agents (except tofacitinib) as first-line therapy; two-thirds had access after one biologic exposure. Among newer agents, vedolizumab had the widest coverage. For indications of UC and CD, 81% of known lives had access to vedolizumab with no prior biologic exposure required ("No Biologic"), 95% after "No Biologic" + "1 prior Biologic." Geographic variations were identified for coverage patterns. CONCLUSIONS: This US-based healthcare policy analysis points to an increased access to advanced therapies for UC and CD. An individualized, risk-stratified treatment approach integrating advanced therapies, including those recently approved, into treatment pathways for UC and CD is feasible.

Obesity Is Independently Associated With Higher Annual Burden and Costs of Hospitalization in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Approximately 15%-40% patients with inflammatory bowel diseases (IBD) are obese. There is an inconsistent association between obesity and IBD phenotype and course. We conducted a nationally representative cohort study to estimate and compare the burden, costs, and causes for hospitalization in obese vs non-obese patients with IBD. METHODS: Using the Nationwide Readmissions Database 2013, we identified obese (based on administrative claims code) and non-obese patients who had been hospitalized at least once, from January through June 2013, and followed them for re-hospitalization until December 2013. We compared annual burden (total days spent in hospital), costs, causes, and outcomes of hospitalization between obese and non-obese patients after 1:1 propensity score matching. RESULTS: We identified 42,285 patients with IBD, of which 12.4% were obese. After propensity score matching, we included 5128 obese and 5128 non-obese IBD patients in our analysis. Compared to non-obese patients, obese patients spent more days in hospital annually (median, 8 vs 5 days) (P < .01), with higher hospitalization-related costs (median, $17,277 vs $11,847) (P < .01); this pattern persisted in subsets of high-need and high-cost patients. Compared to non-obese patients, obese patients were more likely to be hospitalized with preventable admissions (19% vs 15%) or cardiopulmonary complications (16% vs 12%). CONCLUSIONS: In an analysis of data on patients with IBD from the Nationwide Readmissions Database 2013, we found obesity to be independently associated with higher burden and costs of hospitalizations. Strategies should be considered to target obesity as adjunctive therapy for patients with IBD.

Infections and Cardiovascular Complications are Common Causes for Hospitalization in Older Patients with Inflammatory Bowel Diseases.

Background and Aims: Prevalence of inflammatory bowel diseases (IBD) in older patients is increasing. Risk-benefit trade-offs of therapy are poorly understood in older patients, who may be at higher risk of nonIBD and/or treatment-related complications, rather than disease-related complications. We conducted a nationally representative cohort study to estimate and compare annual burden, costs, and causes for hospitalization in older versus younger patients with IBD. Methods: Using the Nationwide Readmissions Database 2013, we created a cohort of 47,402 patients with IBD who had been hospitalized at least once between January-June 2013 and followed for rehospitalization until December 2013. We estimated annual burden (total days spent in hospital), costs, and causes (based on primary discharge diagnosis) of hospitalization in older (>64y, n = 15,428), middle-age (40-64y, n = 18,476), and younger (<40y, n = 13,498) patients. Results: Older patients with IBD spent more days in hospital annually [median interquartile range : 7 (3-13) days] than middle-age [6 (3-12) days], and younger patients [5 ([3-11) days], with significantly higher hospitalization-related costs $15,078 (7423-30,955) vs $12,921 (6367-28,182) vs.. $10,070 (5192-22,100), P < 0.01. Older patients were significantly more likely to be hospitalized due to serious infections (14.6% vs 10.6% vs 8.4%; P < 0.01) and cardiovascular complications (9.9% vs 4.3% vs 0.8%; P < 0.01), and they were less likely due to IBD-related complications (11.8% vs 23.5% vs 41.4%; P < 0.01). Conclusions: Older IBD patients have higher burden and costs of hospitalization than younger patients, mainly attributed to serious infections and cardiovascular complications, rather than disease-related complications. Careful assessment of comparative risks-benefits of different IBD therapies in older patients is warranted to identify the optimal treatment approach.

Annual Burden and Costs of Hospitalization for High-Need, High-Cost Patients With Chronic Gastrointestinal and Liver Diseases.

BACKGROUND & AIMS: We estimated the annual burden and costs of hospitalization in patients with chronic gastrointestinal and liver diseases, and identified characteristics of high-need, high-cost patients, in a nationally representative sample. METHODS: Using Nationwide Readmissions Database 2013, we identified patients with at least 1 hospitalization between January and June 2013, and a diagnosis of inflammatory bowel diseases (IBDs), chronic liver diseases (CLDs), functional gastrointestinal disorders (FGIDs), gastrointestinal hemorrhage, or pancreatic diseases, with 6 months or more of follow up. We calculated days spent in hospital/month and estimated costs of the entire cohort, and identified characteristics of high-need, high-cost patients (top decile of days spent in hospital/month). RESULTS: Patients with IBD (n = 47,402), CLDs (n = 376,810), FGIDs (n = 351,583), gastrointestinal hemorrhage (n = 190,881), or pancreatic diseases (n = 98,432), hospitalized at least once, spent a median of 6 to 7 days (interquartile range, 3-14 d) in the hospital each year (total for all diseases). Compared to patients in the lowest decile (median, 0.13-0.14 d/mo spent in the hospital), patients in the highest decile spent a median 3.7-4.1 days/month in hospital (total for all diseases), with hospitalization costs ranging from $7502/month to $8925/month and 1 hospitalization every 2 months. Gastrointestinal diseases, infections, and cardiopulmonary causes were leading reasons for hospitalization of these patients. Based on multivariate logistic regression, high-need, high-cost patients were more likely to have Medicare/Medicaid insurance, lower income status, index hospitalization in a large rural hospital, high comorbidity burden, obesity, and infection-related hospitalization. CONCLUSIONS: In a nationwide database analysis of patients with IBD, CLD, FGID, gastrointestinal hemorrhage, or pancreatic diseases hospitalized at least once, we found that a small fraction of high-need, high-cost patients contribute disproportionately to hospitalization costs. Population health management directed toward these patients would facilitate high-value care.