AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Ulcerative Colitis.

BACKGROUND & AIMS: Biomarkers are used frequently for noninvasive monitoring and treatment decision making in the management of patients with ulcerative colitis (UC). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of UC. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis on the clinical performance of serum C-reactive protein (CRP), fecal calprotectin, and fecal lactoferrin as biomarkers of disease activity in patients with established UC in symptomatic remission or with active symptoms. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of biomarkers for monitoring and management of UC and provided implementation considerations for clinical practice. RESULTS: The guideline panel made 7 conditional recommendations. In patients with UC in symptomatic remission, the panel suggests the use of a biomarker- and symptom-based monitoring strategy over a symptom-based monitoring strategy. For patients in symptomatic remission, the panel suggests using fecal calprotectin <150 µg/g, normal fecal lactoferrin, and/or normal CRP to rule out active inflammation and avoid routine endoscopic assessment of disease. In patients with UC with moderate to severe symptoms, the panel suggests using fecal calprotectin >150 µg/g, elevated fecal lactoferrin, or elevated CRP to inform treatment decisions and avoid routine endoscopic assessment of disease. However, in patients in symptomatic remission but elevated biomarkers, and in patients with moderate to severe symptoms with normal biomarkers, the panel suggests endoscopic assessment of disease to inform treatment decisions. In patients with UC with mild symptoms, the panel suggests endoscopic assessment of disease activity to inform treatment decisions. The panel identified the use of a biomarker-based monitoring strategy over an endoscopy-based monitoring strategy as a knowledge gap. The panel also proposed key implementation considerations for optimal use of biomarkers, and identified areas for future research. CONCLUSIONS: In patients with UC, noninvasive biomarkers, including fecal calprotectin, fecal lactoferrin, and serum CRP can inform disease monitoring and management.

AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn's Disease.

BACKGROUND & AIMS: Biomarkers are used frequently for evaluation and monitoring of patients with Crohn's disease (CD). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of CD. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to formulate patient-centered clinical questions and review evidence on the performance of fecal calprotectin, serum C-reactive protein (CRP), and Endoscopic Healing Index in patients with established CD who were asymptomatic, had symptoms of varying severity, or were in surgically induced remission. Biomarker performance was assessed against the gold standard of endoscopic activity, defined as a Simple Endoscopic Score for Crohn's Disease ≥3. The panel used the Grading of Recommendations Assessment, Development and Evaluation Evidence-to-Decision framework to develop recommendations for use of biomarkers in various settings. Implementation considerations were formulated for each recommendation to inform clinical practice. RESULTS: The guideline panel made 11 conditional recommendations. In patients with CD in symptomatic remission, the panel suggests use of a biomarker- and symptom-based monitoring strategy over symptoms alone. In patients in symptomatic remission, a fecal calprotectin <150 µg/g and normal CRP rules out active inflammation, avoiding endoscopic evaluation for assessment of disease activity. However, elevated biomarkers in this setting merit confirmation with endoscopy before treatment adjustment. In patients with CD with mild symptoms, neither normal nor elevated biomarkers alone are sufficiently accurate to determine endoscopic activity. In patients with CD with moderate to severe symptoms, elevated fecal calprotectin or serum CRP suggests endoscopic activity, precluding routine endoscopic assessment for disease activity. In patients with CD in surgically induced remission in low-risk patients on pharmacologic prophylaxis, a normal fecal calprotectin reliably rules out endoscopic recurrence. In other postoperative settings, the panel suggests endoscopic assessment for establishing postoperative recurrence. CONCLUSIONS: In patients with CD, fecal calprotectin and serum CRP can inform disease management in both asymptomatic and symptomatic disease. Discordance between symptom assessment and biomarker value may merit endoscopic evaluation for confirmation of status of disease activity.

Gender Related Differences in Surgeon Compensation: Survey Results from the American Society of Colon and Rectal Surgeons.

OBJECTIVE: We sought to understand the effect of sex on compensation among colorectal surgeons and to determine which factors contribute to gender-based differences in compensation. SUMMARY OF BACKGROUND DATA: The sex-based wage gap in the medical profession is among the most pronounced wage gaps in the U.S. Data regarding the wage gap among colorectal surgeons and the underlying reasons for this disparity remain unclear. METHODS: The Healthcare Economics Committee of the American Society of Colon and Rectal Surgeons conducted a survey to evaluate surgeon demographics, compensation, and practice characteristics. To evaluate the effect of sex on compensation, we performed multivariable linear regression with backward selection. We used a two-sided P -value with a significance threshold <0.05. RESULTS: The mean difference in normalized total compensation between men and women was $46,250, and when salary was adjusted for FTEs, the difference was $57,000. Women were more likely to perform anorectal surgery, less likely to perform general surgery and less likely to hold positions in leadership. After adjustments, women reported significantly lower compensation (aOR, 0.88; 95% CI, 0.80-0.97). Time spent doing abdominal surgery (aOR, 1.13; 95% CI 1.03-1.23), professor status (aOR, 1.17; 95% CI, 1.03-1.32) and instructor status (aOR, 1.49; 95% 1.28-1.73) were independently associated with compensation. CONCLUSIONS: We found a 12% adjusted sex wage gap among colorectal surgeons. Gender-based differences in leadership positions and allocation of effort may contribute. Further research will be necessary to clarify sources of wage inequalities. Still, our results should prompt expedient actions to support closing the gap.

Proactive Therapeutic Drug Monitoring Versus Conventional Management for Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Proactive therapeutic drug monitoring (TDM) has been proposed to improve outcomes in patients with inflammatory bowel disease (IBD) treated with tumor necrosis factor (TNF)α antagonists. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing proactive TDM with conventional management in patients with IBD. METHODS: We identified RCTs in patients with IBD treated with TNFα antagonists comparing proactive TDM (routine assessments of trough concentration with dose adjustments to maintain predetermined trough concentration, regardless of disease activity) with conventional management (clinically driven dose adjustments). The primary outcome was failure to maintain clinical remission. Certainty of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: On meta-analysis of 9 RCTs (8 RCTs in adults, and focusing on maintenance phase), there was no significant difference in the risk of failing to maintain clinical remission in patients who underwent proactive TDM (267/709; 38%) vs conventional management (292/696; 42%) (relative risk [RR], 0.96; 95% confidence interval [CI], 0.81-1.13) with moderate heterogeneity (inconsistency index = 36%) (Grading of Recommendations, Assessment, Development and Evaluations; low certainty evidence), with no differences in patients with Crohn's disease (RR, 0.87 ; 95% CI, 0.66-1.15) and ulcerative colitis (RR, 0.88; 95% CI, 0.72-1.07). Disease duration, concomitant immunomodulators, disease activity at baseline, and optimization of therapy before randomization did not modify this association. No differences were observed in risk of developing antidrug antibodies or serious adverse events. Patients in the proactive TDM arm were more likely to undergo dose escalation (RR, 1.56; 95% CI, 1.25-1.94). CONCLUSIONS: Routine proactive TDM to target biologic concentration to specific thresholds, regardless of disease activity, did not offer clinical benefit in patients with IBD treated with TNFα antagonists in RCTs conducted to date. We cannot exclude the possibility of benefit in disease subtypes and phases of therapy (induction) not represented in these RCT populations.

Effectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study.

BACKGROUND & AIMS: There are limited data on outcomes of biologic therapy in Hispanic patients with inflammatory bowel diseases (IBDs). We compared risk of hospitalization, surgery, and serious infections in Hispanic vs non-Hispanic patients with IBD in a multicenter, electronic health record-based cohort of biologic-treated patients. METHODS: We identified adult patients with IBD who were new users of biologic agents (tumor necrosis factor α [TNF-α] antagonists, ustekinumab, vedolizumab) from 5 academic institutions in California between 2010 and 2017. We compared the risk of all-cause hospitalization, IBD-related surgery, and serious infections in Hispanic vs non-Hispanic patients using 1:4 propensity score matching and survival analysis. RESULTS: We compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% TNF-α antagonist-treated; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% TNF-α antagonist-treated; 27% with prior biologic exposure). After propensity score matching, Hispanic patients were younger (37 ± 15 vs 40 ± 16 y; P = .02) and had a higher burden of comorbidities (Elixhauser index, >0; 37% vs 26%; P < .01), without any differences in patterns of medication use, burden of inflammation, and hospitalizations. Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01-1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07-3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99-3.05). CONCLUSIONS: In a multicenter, propensity score-matched cohort of biologic-treated patients with IBD, Hispanic patients experienced higher rates of hospitalization, surgery, and serious infections. Future studies are needed to investigate the biological, social, and environmental drivers of these differences.

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.

Financial Hardship From Medical Bills Among Adults With Chronic Liver Diseases: National Estimates From the United States.

BACKGROUND AND AIMS: Chronic liver diseases (CLD) affect approximately 2% of the U.S. population and are associated with substantial burden of hospitalization and costs. We estimated the national burden and consequences of financial hardship from medical bills in individuals with CLD. APPROACH AND RESULTS: Using the National Health Interview Survey from 2014 to 2018, we identified individuals with self-reported CLD. We used complex weighted survey analysis to obtain national estimates of financial hardship from medical bills and other financial toxicity measures (eg, cost-related medication nonadherence, personal and/or health care-related financial distress, food insecurity). We evaluated the association of financial hardship from medical bills with unplanned health care use and work productivity, accounting for differences in age, sex, race/ethnicity, insurance, income, education, and comorbidities. Of the 3,666 (representing 5.3 million) U.S. adults with CLD, 1,377 (representing 2 million [37%, 95% CI: 35%-39%]) reported financial hardship from medical bills, including 549 (representing 740,000 [14%, 95% CI: 13%-16%]) who were unable to pay medical bills at all. Adults who were unable to pay medical bills had 8.4-times higher odds of cost-related medication nonadherence (adjusted OR [aOR], 8.39 [95% CI, 5.72-12.32]), 6.3-times higher odds of financial distress (aOR, 6.33 [4.44-9.03]), and 5.6-times higher odds of food insecurity (aOR, 5.59 [3.74-8.37]), as compared to patients without financial hardship from medical bills. Patients unable to pay medical bills had 1.9-times higher odds of emergency department visits (aOR, 1.85 [1.33-2.57]) and 1.8-times higher odds of missing work due to disease (aOR, 1.83 [1.26-2.67]). CONCLUSIONS: One in 3 adults with CLD experience financial hardship from medical bills, and frequently experience financial toxicity and unplanned healthcare use. These financial determinates of health have important implications in the context of value-based care.

Patient-Reported Outcomes and Risk of Hospitalization and Readmission in Patients with Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: Patient-reported outcome measures (PROMs) provide a wholesome view of patient well-being. We conducted a retrospective cohort study to evaluate whether PROMs inform risk of unplanned healthcare utilization in patients with IBD. METHODS: We identified adult patients with IBD who completed at least two surveys in a large Internet-based cohort within 1 year. We evaluated the association between baseline patient characteristics, disease activity indices, medication use, and PROMs, assessed using NIH Patient-Reported Outcome Measurement Information System (PROMIS) and subsequent risk of incident hospitalization (at time of first follow-up) within 1 year, and readmission within 1 year (in patients with hospitalization at first follow-up), using multivariable logistic regression. RESULTS: Of 7902 patients with IBD (45.5 year, 72% females, 63% Crohn's disease), 1377 (17.4%) were hospitalized within 1 year. Among PROMs, pain interference (adjusted OR per 5-point increase in PROMIS, 1.09; 95% CI 1.05-1.14), but not depression, anxiety, fatigue or sleep disturbance, was predictive of higher risk of hospitalization. Prior surgery or hospitalization, symptomatic disease, biologic, and corticosteroid use were also associated with higher risk of hospitalization. Of 521 patients hospitalized with IBD, 133 (25.5%) were readmitted within 1 year. Anxiety and pain interference were predictive of higher risk of readmission, whereas depression was associated with lower risk of readmission. CONCLUSIONS: In a large Internet-based cohort study, PROMs may have a modest effect on modifying risk of unplanned healthcare utilization in patients with IBD, with pain interference being most consistently associated with increased risk of hospitalization and readmission.

Systematic Review and Meta-Analysis: Risk of Hospitalization in Patients with Ulcerative Colitis and Crohn's Disease in Population-Based Cohort Studies.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) lead to high morbidity and unplanned healthcare utilization. We conducted a systematic review with meta-analysis to estimate the cumulative incidence of IBD-related (and all-cause) hospitalization in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Through a systematic review to September 3, 2019, we identified population-based inception cohort studies in patients with IBD that reported patient-level cumulative incidence of hospitalization at 1, 3 and 5 years after diagnosis. Hospitalization risk was pooled using random effects meta-analysis, and risk factors analyzed through mixed-effects meta-regression and qualitative synthesis. RESULTS: In patients with UC (6 cohorts), 1-, 3- and 5-year risk of UC-related hospitalization was 10.4% (95% CI 8.2-13.2), 17.0% (95% CI 14.0-20.4) and 21.5% (95% CI 18.0-25.4), respectively, with considerable heterogeneity. In patients with CD (6 cohorts), 1-, 3- and 5-year risk of CD-related hospitalization was 29.3% (95% CI 20.0-40.8), 38.5% (95% CI 26.8-51.7) and 44.3% (95% CI 32.7-56.5), respectively, with considerable heterogeneity. On meta-regression, steady decline in risk of hospitalization was observed in patients diagnosed in a more contemporary era. Younger age at onset (both UC and CD), extensive colitis (UC), ileal-dominant CD, perianal CD and penetrating and/or stricturing behavior (CD) and early need for corticosteroids and immunosuppressive therapy (both UC and CD) were associated with increased risk of hospitalization. CONCLUSION: Approximately one in five and one in two patients with UC and CD are hospitalized within 5 years of diagnosis, respectively. Population health management strategies are required to mitigate unplanned healthcare utilization.

Impact of Comorbid Psychiatric Disorders on Healthcare Utilization in Patients with Inflammatory Bowel Disease: A Nationally Representative Cohort Study.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) frequently experience comorbid psychiatric disorders, which negatively impact quality of life. We characterized the longitudinal burden of hospitalization-related healthcare utilization in adults with IBD with and without comorbid anxiety, depression, or bipolar disorder. METHODS: In the 2017 Nationwide Readmissions Database (NRD), we identified 40,177 patients with IBD who were hospitalized between January 1, 2017 and June 30, 2017 and who were followed until December 31, 2017. In this cohort, we compared the annual burden (i.e., total days spent in hospital), costs, risk of readmission, inpatient mortality, and IBD-related surgery in patients with and without comorbid psychiatric disorders (anxiety, depression, or bipolar disorder). RESULTS: Of the 40,177 adults who were hospitalized for IBD, 25.7% had comorbid psychiatric disorders. Over a 10 month-long period of follow-up, patients with comorbid psychiatric disorders spent more days in the hospital (median, 7 days vs. 5 days, p < 0.01), experienced higher 30-day (31.3 vs. 25.4%; p < 0.01) and 90-day (42.6 vs. 35.3%, p < 0.01) readmission rates, and had higher hospitalization-related costs (median, $41,418 vs. $39,242, p < 0.01). However, they were less likely to undergo IBD-related procedures or surgeries. There were no differences in risk of mortality. On Cox proportional hazard analysis, the presence of comorbid psychiatric disorders was associated with a 16% higher risk of readmission (HR, 1.16; 95% CI, 1.13-1.20) and a 13% higher risk of severe IBD-related hospitalization (HR, 1.13; 95% CI, 1.08-1.16). CONCLUSIONS: In adults with IBD, comorbid psychiatric disorders were independently associated with a higher burden and cost of hospitalization, without an increase in the risk of IBD-related surgery or procedures. Population-based interventions aimed at treating psychiatric comorbidities may decrease the risk of unplanned healthcare utilization.

Frailty Is Independently Associated with Mortality and Readmission in Hospitalized Patients with Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Old age must be considered in weighing the risks of complications vs benefits of treatment for patients with inflammatory bowel diseases (IBD). We conducted a nationally representative cohort study to estimate the independent effects of frailty on burden, costs, and causes for hospitalization in patients with IBD. METHODS: We searched the Nationwide Readmissions Database to identify 47,402 patients with IBD, hospitalized from January through June 2013 and followed for readmission through December 31, 2013. Based on a validated hospital frailty risk scoring system, 15,507 patients were considered frail and 31,895 were considered non-frail at index admission. We evaluated the independent effect of frailty on longitudinal burden and costs of hospitalization, inpatient mortality, risk of readmission and surgery, and reasons for readmission. RESULTS: Over a median follow-up time of 10 months, adjusting for age, sex, income, comorbidity index, depression, obesity, severity, and indication for index hospitalization, frailty was independently associated with 57% higher risk of mortality (adjusted hazard ratio [aHR], 1.57; 95% CI, 1.34-1.83), 21% higher risk of all-cause readmission (adjusted hazard ratio [HR], 1.21; 95% CI, 1.17-1.25), and 22% higher risk of readmission for severe IBD (aHR, 1.22; 95% CI, 1.16-1.29). Frail patients with IBD spent more days in the hospital annually (median 9 days; interquartile range, 4-18 days vs median 5 days for non-frail patients; interquartile range, 3-10 days; P < .01) with higher costs of hospitalization ($17,791; interquartile range, $8368-$38,942 vs $10,924 for non-frail patients, interquartile range, $5571-$22,632; P < .01). Infections, rather than IBD, were the leading cause of hospitalization for frail patients. CONCLUSIONS: Frailty is independently associated with higher mortality and burden of hospitalization in patients with IBD; infections are the leading cause of hospitalization. Frailty should be considered in treatment approach, especially in older patients with IBD.

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.

Baseline Clearance of Infliximab Is Associated With Requirement for Colectomy in Patients With Acute Severe Ulcerative Colitis.

BACKGROUND & AIMS: Hospitalized patients with acute severe ulcerative colitis (ASUC) often require surgery. Although the tumor necrosis factor antagonist infliximab is an effective salvage therapy to prevent colectomy in patients with ASUC, optimal dosing is unclear. Calculated infliximab clearance has been associated with important outcomes in patients with ulcerative colitis, but its utility in patients with ASUC has not been established. We assessed the relationship between calculated the baseline infliximab clearance before infliximab salvage therapy and the requirement for colectomy in patients hospitalized for ASUC. METHODS: We obtained data from hospitalized patients with ASUC who initiated infliximab therapy. We then calculated the baseline infliximab drug clearance in these patients based on an existing formula. The primary aim was to compare clearance between patients who required colectomy 6 months later and patients who did not require colectomy. Receiver operating characteristic curve analyses evaluated clearance thresholds for colectomy. Multivariable logistic regression analysis evaluated factors associated with colectomy. RESULTS: In 39 patients with ASUC, the median baseline calculated clearance was higher in patients requiring colectomy at 6 months than in patients without colectomy (0.733 vs 0.569 L/d; P = .005). An infliximab clearance threshold of 0.627 L/d identified patients who required colectomy with 80.0% sensitivity and 82.8% specificity (area under the curve, 0.80). A higher proportion of patients with infliximab clearance of 0.627 L/d or more underwent colectomy within 6 months (61.5%) than patients with lower infliximab clearance values (7.7%) (P = .001). Multivariable analysis identified baseline infliximab clearance as the only factor associated with colectomy. The infliximab dose in the hospital was higher in patients who required colectomy. Results were similar at 30 days and 1 year. CONCLUSIONS: In patients hospitalized with ASUC, higher values of calculated infliximab clearance before infliximab administration is associated with higher rates of colectomy. Although patients who required colectomies received higher doses, data on infliximab concentrations are lacking. Infliximab pharmacokinetic models are needed for patients with ASUC to allow comparative trials on clearance-based vs standard dosing.

Trends in the Economic Burden of Chronic Liver Diseases and Cirrhosis in the United States: 1996-2016.

INTRODUCTION: The management of chronic liver diseases (CLDs) and cirrhosis is associated with substantial healthcare costs. We aimed to estimate trends in national healthcare spending for patients with CLDs or cirrhosis between 1996 and 2016 in the United States. METHODS: National-level healthcare expenditure data developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project and prevalence of CLDs and cirrhosis derived from the Global Burden of Diseases Study were used to estimate temporal trends in inflation-adjusted US healthcare spending, stratified by setting of care (ambulatory, inpatient, emergency department, and nursing care). Joinpoint regression was used to evaluate temporal trends, expressed as annual percent change (APC) with 95% confidence intervals (CIs). Drivers of change in spending for ambulatory and inpatient services were also evaluated. RESULTS: Total expenditures in 2016 were $32.5 billion (95% CI, $27.0-$40.4 billion). Over 65% of spending was for inpatient or emergency department care. From 1996 to 2016, there was a 4.3%/year (95% CI, 2.8%-5.8%) increase in overall healthcare spending for patients with CLDs or cirrhosis, driven by a 17.8%/year (95% CI, 14.5%-21.6%) increase in price and intensity of hospital-based services. Total healthcare spending per patient with CLDs or cirrhosis began decreasing after 2008 (APC -1.7% [95% CI, -2.1% to -1.2%]), primarily because of reductions in ambulatory care spending (APC -9.1% [95% CI, -10.7% to -7.5%] after 2011). DISCUSSION: Healthcare expenditures for CLDs or cirrhosis are substantial in the United States, driven disproportionately by acute care in-hospital spending.

Positioning Therapies in the Management of Crohn's Disease.

In the past decade, several new therapies with different mechanisms of action have been approved for the management of moderate to severe Crohn's disease. However, there is limited guidance on optimal positioning of agents as first- or second-line therapies because of the absence of head-to-head trials. Furthermore, given the lack of comparative studies, treatment guidelines have provided limited insight. In this review, we discuss data on key treatment attributes, comparative efficacy and safety, factors predictive of response to each agent, and propose an algorithm for positioning therapies for the management of patients with low-risk and high-risk Crohn's disease.

Rate of Risk Factors for and Interventions to Reduce Hospital Readmission in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: We investigated 30- and 90-day rates and causes of, risk factors for, and interventions to reduce hospital readmission in patients who received medical treatment for inflammatory bowel diseases (IBD). METHODS: We performed a systematic search of publications through July 1, 2018 for studies of rates of hospital readmission and associated causes and risk factors in patients who received medical treatments for IBD. Our final analysis included 17 cohort studies (6324 patients) of hospitalized adults with IBD who had received medical treatment, along with reported readmission rates with detailed chart review. We performed random effects meta-analysis to estimate 30- and 90-day rates of readmission and identified causes and risk factors associated with readmission. We also performed qualitative analyses of studies that focused on interventions to reduce readmission. RESULTS: Overall, the 30-day rate of readmission was 18.1% (95% CI, 14.4-22.4) and the 90-day rate was 26.0% (95% CI, 22.7-29.6). On meta-regression, studies with higher proportions of patients with ulcerative colitis than Crohn's disease reported higher risks for readmission. Most common reasons for readmission were IBD flare, infection, or complications from unplanned surgeries during hospitalizations. Consistent risk factors for 30-day readmission were admission for pain control (odds ratio [OR], 2.27; 95% CI, 1.69-3.03), need for total parenteral nutrition on discharge (OR, 2.13; 95% CI, 1.36-3.35), and prior or unplanned surgery during admission (OR, 3.11; 95% CI, 2.27-4.25). Only 1 study focused on interventions (specialized inpatient IBD service) to reduce risk of readmission. CONCLUSIONS: Overall 30- and 90-day rates of readmission for patients who received medical treatment for IBD are 18.1% and 26.0%, respectively. IBD flares and infections are common reasons for readmission, and inadequate pain control and need for parenteral nutrition were common risk factors. Interventional studies to reduce risk of readmission are needed.

Incorporating Fecal Calprotectin Into Clinical Practice for Patients With Moderate-to-Severely Active Ulcerative Colitis Treated With Biologics or Small-Molecule Inhibitors.

INTRODUCTION: We applied the Grading of Recommendations, Assessment, Development, and Evaluation framework to evaluate the performance of fecal calprotectin (FC) as an alternative to endoscopy in patients with moderate-to-severe ulcerative colitis (UC) treated with a biologic agent or tofacitinib. METHODS: Individual participant data from the trials of infliximab, golimumab, vedolizumab, and tofacitinib for UC were pooled to generate prevalence of endoscopic activity (Mayo endoscopy score) across different combinations of the rectal bleeding score (RBS) and stool frequency score (SFS). These estimates were then combined with the data from an updated systematic review of the operating properties of FC to generate clinical scenario-specific assessments of the performance of FC as a predictor of endoscopic disease activity. A prespecified threshold of acceptability for false-negative (FN) and false-positive (FP) test results was set at 5%. RESULTS: For patients with UC achieving RBS 0 + SFS 0/1, FC ≤ 50 µg/g may avoid endoscopy in 50% patients with a FN rate <5%. Similarly, for patients with RBS 2/3 + SFS 2/3, FC ≥ 250 µg/g potentially avoids endoscopy in approximately 50% patients with an FP rate <5%. The greatest uncertainty in the diagnostic performance for FC was observed in patients with UC achieving RBS 0 but having SFS 2/3, where FN and FP rates were consistently >10%, and endoscopic evaluation may be warranted. DISCUSSION: Two clinical scenarios were identified where FC can be used with confidence for monitoring treatment response to biologics or tofacitinib in patients with UC without the requirement for endoscopy.

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.

Impact of Obesity on Disease Activity and Patient-Reported Outcomes Measurement Information System (PROMIS) in Inflammatory Bowel Diseases.

INTRODUCTION: We conducted a cohort study on the impact of obesity on disease activity and Patient-Reported Outcomes Measurement Information System (PROMIS) measures in the inflammatory bowel disease (IBD) Partners cohort. METHODS: We performed a cross-sectional and longitudinal study within IBD Partners, an internet-based cohort of >15,000 patients living with Crohn's disease (CD) and ulcerative colitis (UC). We included adult patients with IBD, with recorded body mass index (BMI), with at least 6 months of follow-up, excluding patients with BMI < 18.5 kg/m. We evaluated the independent effect of World Health Organization classes of obesity on risk of clinical relapse or persistent disease activity (using validated disease activity indexes) and PROMIS measures, using multivariate logistic regression and linear regression, respectively. RESULTS: We included 7,296 patients with IBD (4,748 patients with CD, 19.5% obese; 2,548 patients with UC with intact colon, 20.3% obese). Obesity was independently, and in a dose-dependent fashion, associated with an increased risk of persistent disease activity or relapse in both patients with CD (class II or III obesity vs normal BMI: adjusted odds ratio, 1.86; 95% confidence interval, 1.30-2.68) and UC (adjusted odds ratio, 2.97; 95% confidence interval, 1.75-5.17). Obesity was also independently associated with higher anxiety, depression, fatigue, pain, and inferior social function scores in patients with CD and UC at baseline and with worsening depression, fatigue, pain, and social function in patients with CD on longitudinal assessment. DISCUSSION: Obesity at baseline is independently associated with worsening disease activity and PROMIS measures in patients with IBD.

Comparison of Multiplex Gastrointestinal Pathogen Panel and Conventional Stool Testing for Evaluation of Diarrhea in Patients with Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: Gastrointestinal pathogen panels (GPPs) are increasingly being used for evaluation of diarrhea. The impact of these tests on patients with inflammatory bowel diseases (IBD) is unknown. We performed a time-interrupted cohort study comparing GPPs and conventional stool evaluation in patients with IBD with diarrhea. METHODS: We included 268 consecutive patients with IBD who underwent GPP (BioFire Diagnostics®) (n = 134) or conventional stool culture and Clostridium difficile polymerase chain reaction testing (n = 134) during suspected IBD flare between 2012 and 2016. Primary outcome was composite of 30-day IBD-related hospitalization, surgery, or emergency department visit; secondary outcome was IBD treatment modification. RESULTS: Overall, 41/134 (30.6%) patients tested positive on GPP (18 C. difficile, 17 other bacterial infections, and 6 viral pathogens) versus 14/134 patients (10.4%, all C. difficile) testing positive on conventional testing. Rate of IBD treatment modification in response to stool testing was lower in GPP group as compared conventional stool testing group (35.1 vs. 64.2%, p < 0.01). On multivariate analysis, diagnostic evaluation with GPP was associated with three times higher odds of IBD-related hospitalization/surgery/ED visit (95% CI, 1.27-7.14), as compared to conventional stool testing. This negative impact was partly mediated by differences in ordering provider specialty, with non-gastroenterologists more likely to order GPP as compared to gastroenterologists. CONCLUSIONS: In patients with suspected flare of IBD, GPPs have higher pathogen detection rate and lead to lower rate of IBD treatment modification. A diagnostic testing strategy based on GPPs is associated with higher hospital-related healthcare utilization as compared to conventional stool testing, particularly when utilized by non-gastroenterologists.