The burden of nonalcoholic steatohepatitis (NASH) in the United States.

BACKGROUND: There is limited data on the comparative economic and humanistic burden of non-alcoholic steatohepatitis (NASH) in the United States. The objective was to examine the burden of disease comparing NASH to a representative sample of the general population and separately to a type 2 diabetes mellitus (T2DM) cohort by assessing health-related quality of life (HRQoL) measures, healthcare resource use (HRU) and work productivity and activity impairment (WPAI). METHODS: Data came from the 2016 National Health and Wellness Survey, a nationally representative patient-reported outcomes survey conducted in the United States. Respondents with physician-diagnosed NASH, physician-diagnosed T2DM, and respondents from the general population were compared. Humanistic burden was examined with mental (MCS) and physical (PCS) component summary scores from the Short-Form (SF)-36v2, concomitant diagnosis of anxiety, depression, and sleep difficulties. Economic burden was analysed based on healthcare professional (HCP) and emergency room (ER) visits, hospitalizations in the past six months; absenteeism, presenteeism, overall work impairment, and activity impairment scores on WPAI questionnaire. Bivariate and multivariable analysis were conducted for each outcome and matched comparative group. RESULTS: After adjusting for baseline demographics and characteristics, NASH (N = 136) compared to the matched general population cohort (N = 544), reported significantly lower (worse) mental (MCS 43.19 vs. 46.22, p = 0.010) and physical (PCS 42.04 vs. 47.10, p < 0.001) status, higher % with anxiety (37.5% vs 25.5%, p = 0.006) and depression (43.4% vs 30.1%, p = 0.004), more HCP visits (8.43 vs. 5.17), ER visits (0.73 vs. 0.38), and hospitalizations (0.43 vs. 0.2) all p's < 0.05, and higher WPAI scores (e.g. overall work impairment 39.64% vs. 26.19%, p = 0.011). NASH cohort did not differ from matched T2DM cohort (N = 272) on mental or work-related WPAI scores, but had significantly worse physical status (PCS 40.52 vs. 44.58, p = 0.001), higher % with anxiety (39.9% vs 27.8%, p = 0.043), more HCP visits (8.63 vs. 5.68, p = 0.003) and greater activity impairment (47.14% vs. 36.07%, p = 0.010). CONCLUSION: This real-world study suggests that burden of disease is higher for all outcomes assessed among NASH compared to matched general controls. When comparing to T2DM, NASH cohort has comparable mental and work-related impairment but worse physical status, daily activities impairment and more HRU.

The Cost of Diagnosing and Managing Non-alcoholic Steatohepatitis in Europe and the United States.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) is acknowledged as a severe disease that is associated with a significant burden on patients, payers, and society. However, limited evidence exists on the cost associated with NASH across different countries. This analysis aims to describe the cost associated with the routine care of patients with NASH in France, Germany, and the United States. METHODS: Data was sourced from the Gesellschaft für Konsumforschung (now Ipsos) Disease Atlas Real- World Evidence program collected from July through November 2017 in France, Germany, and the United States. Country-level unit cost was estimated from national databases for diagnostic tests and procedures, prescription drugs, hospital stays, and outpatient visits in respective local currency based on 2017 values. These were combined to provide an estimate of the cost of management of confirmed NASH in this specific patient population and are presented as mean cost per patient per year for each country in local currency and as USD adjusted for purchasing power parity for comparison. RESULTS: Annual mean ± standard deviation cost of non-alcoholic steatohepatitis ranged from purchasing power parity USD 1,049±2,461 in Germany to USD 1,723±2,988 in the United States. In all markets, the predominant contributor to cost is healthcare resource use represented by hospitalisation and outpatient visits. CONCLUSIONS: This study reveals that costs associated with NASH treatment and management vary across the three countries studied, in part due to differences in healthcare systems but also due to different approaches in managing this disease. Our analysis represents the costs for a specific cohort of patients and further studies are warranted to better understand the progressive impact of NASH on healthcare systems and society.

Quantifying spillover benefits in value assessment: a case study of increased graft survival on the US kidney transplant waitlist.

AIM: To quantify the wider impacts of increased graft survival on the size of the kidney transplant waitlist and health and economic outcomes. MATERIALS AND METHODS: The analysis employed known steady-state solutions to a double-queueing system as well as simulations of this system. Baseline input parameters were sourced from the Organ Procurement and Transplant Network and the United States Renal Data System. Three increased graft survival scenarios were modeled: decreases in repeat transplant candidates joining the waitlist of 25%, 50%, and 100%. RESULTS: Under the three scenarios, we estimated that the US waitlist size would decrease from 91,822 to 85,461 (6.9% decrease), 80,073 (12.8% decrease), and 69,340 (24.4% decrease), respectively. Patient outcomes improved, with lifetime quality-adjusted life years (QALYs) for a 1-year cohort of transplant recipients increasing by 10,010, 16,888, and 43,345 over the three scenarios. Discounted lifetime costs for the cohort in the new steady state were lower by $1.6 billion, $2.3 billion, and $9.0 billion for each scenario, respectively. Spillover impacts (i.e. benefits that accrued beyond the patients who directly experienced increased graft survival) accounted for 41-48% of the QALY gains and ranged from cost increases of 3.3% to decreases of 5.5%. LIMITATIONS: The model is a simplification of reality and does not account for the full degree of patient heterogeneity occurring in the real world. Health economic outcomes are extrapolated based on the assumption that the median patient is representative of the overall population. CONCLUSIONS: Increasing graft survival reduces demand from repeat transplants candidates, allowing additional candidates to receive transplants. These spillover impacts decrease waitlist size and shorten wait times, leading to improvements in graft and patient survival as well as quality-of-life. Cost-effectiveness analyses of treatments that increase kidney graft survival should incorporate spillover benefits that accrue beyond the direct recipient of an intervention.

Economic modelling of costs associated with outcomes reported for type 2 diabetes mellitus (T2DM) patients in the CANVAS and EMPA-REG cardiovascular outcomes trials.

AIMS: To model direct medical costs associated with reductions in cardiovascular disease (CVD) events in T2DM patients reported in the CANVAS and EMPA-REG trials, which assessed the cardiovascular safety of canagliflozin and empagliflozin, respectively. MATERIALS AND METHODS: Costs were modeled from a US managed care organization (MCO) perspective for the CVD outcomes included in both trials: three-point major adverse cardiovascular event (MACE) and its components (cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke), as well as heart failure requiring hospitalization. The rate of CVD events averted (difference between study drug and placebo) was projected to the portion of an MCO T2DM population matching the respective trial's inclusion criteria. A targeted literature search for paid amounts directly associated with each CVD event provided the unit costs, which were applied to the projected number of events averted, to calculate costs avoided per member per year (PMPY). One-way sensitivity analyses were performed on events averted, unit costs, and percentages of trial-applicable patients. RESULTS: Based on three-point MACE events averted, costs avoided PMPY of $6.17 (range: $1.27-$10.94) for CANVAS and $2.75 ($0.19-$4.83) for EMPA-REG were estimated. Costs avoided for individual components of MACE ranged from $0.77 to $3.84 PMPY for CANVAS and from -$0.97 (additional costs) to $1.54 for EMPA-REG. PMPY costs avoided for heart failure were $2.72 for CANVAS and $1.32 for EMPA-REG. LIMITATIONS AND CONCLUSIONS: Models assumed independent, non-recurrent outcomes and were restricted to medical costs directly associated with the trial-reported events. The reductions in CVD events in T2DM patients reported for both CANVAS and EMPA-REG project to a positive cost avoidance for these events in an MCO population. The analysis did not include an assessment of the impact on total cost, as the costs associated with adverse events, drug utilization or other clinical outcomes were not examined.

Initial Assessment, Risk Stratification, and Early Management of Acute Nonvariceal Upper Gastrointestinal Hemorrhage.

Inhospital mortality from nonvariceal upper gastrointestinal bleeding has improved with advances in medical and endoscopy therapy. Initial management includes resuscitation, hemodynamic monitoring, proton pump inhibitor therapy, and restrictive blood transfusion. Risk stratification scores help triage bleeding severity and provide prognosis. Upper endoscopy is recommended within 24 hours of presentation; select patients at lowest risk may be effectively treated as outpatients. Emergent endoscopy within 12 hours does not improve clinical outcomes, including mortality, rebleeding, or need for surgery, despite an increased use of endoscopic treatment. There may be a benefit to emergent endoscopy in patients with evidence of active bleeding.

Comparative persistence and adherence with newer anti-hyperglycemic agents to treat patients with type 2 diabetes in the United States.

OBJECTIVES: Non-adherence and non-persistence to anti-hyperglycemic agents are associated with worse clinical and economic outcomes in patients with type 2 diabetes. This study evaluated treatment persistence and adherence across newer anti-hyperglycemic agents (canagliflozin, dapagliflozin, sitagliptin, saxagliptin, linagliptin, liraglutide, or exenatide). METHODS: This retrospective cohort study of Truven Health Analytics Marketscan databases included adult patients with type 2 diabetes whose first pharmacy claim for a newer anti-hyperglycemic agent was between February 1, 2014 and July 31, 2014. Treatment persistence and adherence were assessed for 12 months after the first claim (post-index). Persistence was defined as no gap ≥90 days between the end of one pharmacy claim and the start of the next pharmacy claim post-index. Adherence used two definitions: proportion of days covered (PDC) and medication possession ratio (MPR). Multivariable analyses of non-persistence (hazard ratios) and adherence (odds ratios) were adjusted for baseline demographics, drug cost, clinical characteristics, and other anti-hyperglycemic agents. RESULTS: A total of 11,961 patients met all study selection criteria. Persistence rates at 12 months were significantly greater (p < 0.05 for each comparison) for canagliflozin 100 mg (61%) compared with dapagliflozin 5 mg (40%), dapagliflozin 10 mg (41%), sitagliptin (48%), saxagliptin (42%), linagliptin (52%), liraglutide (47%), exenatide (23%), and long-acting exenatide (39%). The persistence rate was greater (p < 0.05) for canagliflozin 300 mg (64%) vs canagliflozin 100 mg. Median adherence rates for canagliflozin 100 mg (MPR = 0.83; PDC = 0.79) and canagliflozin 300 mg (MPR = 0.92; PDC = 0.81) were greater than for the other index anti-hyperglycemic agents (MPR = 0.33-0.75; PDC = 0.33-0.72). Consistent results for treatment persistence and adherence were observed in multivariable analyses that were adjusted baseline characteristics. CONCLUSIONS: Canagliflozin was associated with better treatment persistence and treatment adherence compared with other anti-hyperglycemic agents in real-world settings.

Economic burden of recurrent venous thromboembolism: analysis from a U.S. hospital perspective.

PURPOSE: An analysis of resource utilization and hospital costs associated with recurrent venous thromboembolism (VTE) is presented. METHODS: A retrospective cohort analysis was conducted using a large U.S. hospital database. Patients with VTE-related hospitalization events during the period January-December 2010 were identified; data collection extended for up to 12 months after the index event. Postdischarge hospital resource use and total costs were compared in cohorts of patients with and without recurrent VTE. Regression analysis was performed to compare hospital costs and length of stay (LOS) during initial and subsequent VTE encounters. RESULTS: Among the study population of 43,734 patients, 4% had postdischarge VTE-related events during the data collection period. The median and mean ± S.D. times to VTE recurrence were 48 days and 98 ± 106 days, respectively. Patients with recurrent VTE had more all-cause hospitalizations than those without recurrent VTE (mean ± S.D., 1.07 ± 0.96 versus 0.15 ± 0.53; p < 0.0001), more all-cause emergency room visits (mean ± S.D., 0.31 ± 0.66 versus 0.05 ± 0.31; p < 0.0001), and greater total costs (mean ± S.D., $28,353 ± $39,624 versus $17,712 ± $33,461; p < 0.0001). Relative to initial VTE admissions, admissions for recurrent VTE were, on average, associated with a 14% longer LOS (p = 0.0002) and a 22% higher total cost (p < 0.001). CONCLUSION: Patients with recurrent VTE used more hospital resources than those without recurrent VTE. Readmissions for VTE were significantly longer and more costly than index encounters.

Predictors of non-adherence to systemic oral therapy for advanced hepatocellular carcinoma.

OBJECTIVES: With increasing use and cost of oral oncology medications, patient non-adherence with oral therapy is of concern. This study evaluated non-adherence among patients receiving first-line oral therapy for hepatocellular carcinoma (HCC). METHODS: This retrospective study used the employer-based MarketScan medical and pharmacy claims database (2005-2011) to identify adult patients with two or more diagnoses of HCC (ICD-9 155), and two or more filled prescriptions for sorafenib. Additional eligibility requirements were not having other previous cancers and a 4 month wash-out period prior to the index sorafenib date. Adherence was assessed using a modified proportion of days covered (PDC) measure with patient-specific sorafenib exposure from index date to treatment discontinuation. Non-adherence was categorized as PDC <85% (base case), with sensitivity analyses using an 80% cut-off and allowance for physician-directed therapy gaps. Logistic regression models were estimated to identify predictors of non-adherence. RESULTS: A total of 1127 patients (median age = 61.0 years; 78.4% male) met eligibility criteria. Median duration of enrollment was 223 days and median sorafenib exposure was 121 days. Between 21.1% (PDC < 0.80) and 28.0% (PDC < 0.85) of patients were non-adherent. Higher age (p = 0.022), number of baseline medications (p = 0.003) and number of baseline comorbidities (p = 0.002) were associated with lower non-adherence, while prior procedures were associated with greater non-adherence (p = 0.002). LIMITATIONS: In this study using billing claims data, we were unable to evaluate patient severity in terms of clinical characteristics such as the Child-Pugh score. Similarly, we could not assess clinical outcomes such as tumor response, radiological progression or overall survival, although median duration of sorafenib exposure and duration of health plan enrollment respectively were found to be good proxies. CONCLUSIONS: Using a modified PDC approach, 22-29% of patients were non-adherent. Identified predictors of non-adherence in HCC should be assessed for newly emerging oral therapies, and may be used to guide patient education and other adherence-enhancing initiatives.