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.

Assessing physician preferences on future therapeutic options and diagnostic practices in non-alcoholic steatohepatitis.

BACKGROUND & AIMS: There is currently no data on physician preferences regarding future therapies for non-alcoholic steatohepatitis (NASH); this study explores these preferences and characteristics that are relevant to physician decision-making when choosing a potential therapy for a patient with NASH. The results were compared with those from a similar patient preference survey which was conducted in parallel. METHOD: Initial exploratory 30-minute telephone interviews were conducted to inform the design of a 15-minute quantitative online specialist physicians survey, containing direct questions and a preference survey. This was based on a best-worst scaling (BWS) experiment to assess the relative importance of different treatment characteristics (attributes), followed by several paired comparison questions to understand the preference for 5 hypothetical product profiles. RESULTS: The answers come from 121 physicians from Canada (n = 31), Germany (n = 30), the UK (n = 30) and the USA (n = 30). The primary driving element in NASH treatment decision-making was efficacy (49.23%), defined as "[hypothetical product] impact on liver status" and "[slowing of] progression to cirrhosis". Physicians reported the common use of non-invasive NASH diagnostic tests and 81% reported performing liver biopsy. In 57% of cases, physicians reported that "concerns related to the available diagnostic methods" limit the number of patients with biopsy-confirmed NASH. CONCLUSIONS: This first physician preference study reveals that efficacy will be the main driver for physicians in selecting future NASH drugs. The findings also confirm the widespread use of non-invasive diagnostic tests and the reluctance to perform confirmatory liver biopsy despite guideline recommendations, mainly due to limited therapeutic options and patient refusal. LAY SUMMARY: This study explores physician preferences in relation to future therapies for non-alcoholic steatohepatitis (NASH) and characteristics that are relevant to physician decision-making when choosing a potential therapy for a patient with NASH. The results of a short online survey completed by 121 specialist physicians determined that the primary factor that influences treatment decision-making is efficacy, and that a wide range of non-invasive techniques are used to diagnose NASH, while confirmatory liver biopsy is not performed by all physicians despite guideline recommendations.

Understanding Patient Preferences and Unmet Needs in Non-alcoholic Steatohepatitis (NASH): Insights from a Qualitative Online Bulletin Board Study.

INTRODUCTION: The aim of this work was to understand how patients with non-alcoholic steatohepatitis (NASH) perceive their disease, unmet needs, and expectations regarding future treatment through online bulletin board (OBB) qualitative research. METHODS: OBB is an asynchronous online qualitative market research tool that provides an open forum for interactive discussion among participants. Patients with NASH were recruited via physician referral and completed a screener questionnaire to ensure their eligibility and willingness to participate. A trained moderator managed the discussion that allowed open answers and responses to other participants' posts. Patient responses were analyzed using a combination of different qualitative analytical tools. RESULTS: The OBB ran for 4 days and included 16 patients (n = 8, UK; n = 8, US) with NASH (fibrosis stages F1-F3) and comorbidities including diabetes/prediabetes (n = 9) and obesity (n = 12). The key insights were (1) patients with NASH have a poor understanding of the disease, its progression, and management-they feel a lack of adequate educational support from their physicians; (2) diagnosis of NASH is incidental in most cases, mainly because patients fail to spontaneously associate their signs or symptoms with their liver condition; (3) comorbidities (obesity and diabetes) are more concerning to patients than NASH; and (4) patients perceive that NASH impacts their social life and work performance in more advanced stages. CONCLUSIONS: This OBB provided valuable patient insights into NASH disease perception and management and revealed unmet need areas. In light of no approved therapies, these patient insights can inform early drug development strategies and stakeholder discussions on NASH. FUNDING: Novartis Pharma AG, Basel.

Health care burden and treatment patterns in commercially insured children with chronic idiopathic/spontaneous urticaria: A real-world study in the United States.

BACKGROUND: Chronic idiopathic urticaria (CIU)/spontaneous urticaria (CSU) is defined by the presence of wheals, angioedema, or both for ≥6 weeks, with or without an identifiable trigger. Real-world health care data among children with CIU/CSU remain scarce. OBJECTIVES: To describe treatment patterns, health care resource utilization (HRU), and costs in pediatric patients with CIU/CSU (<12 years old) and to compare these with pediatric patients without CIU/CSU. METHODS: A commercial administrative claims data base (September 2013 to June 2016) was used. The CIU/CSU cohort included pediatric patients with either two or more claims for a diagnosis of urticaria ≥6 weeks apart or one or more claims for a diagnosis of urticaria and one or more claims for a diagnosis of angioedema ≥6 weeks apart (index was defined as the first claim). The control cohort comprised pediatric patients without urticaria or angioedema (index randomly assigned). Patients with <6 months of eligibility before and after the index date were excluded. HRU and costs were compared between the cohorts during the observation period after propensity score matching. RESULTS: A total of 6109 pediatric patients with CIU/CSU were selected, and 6107 were 1:1 matched with controls. The patients with CIU/CSU who had a mean ± standard deviation age of 4.58 ± 3.36 years, and 47.9% were girls. CIU/CSU-related medication use increased after diagnosis (e.g., baseline versus 6-month follow-up, 2.2 versus 8.0% for nonsedating prescription H1 antihistamines; 7.4 versus 17.4% for oral corticosteroids). Relative to the controls, the patients with CIU/CSU had higher rates of HRU (incidence rate ratios of 1.71, 2.39, and 2.07 for inpatient, emergency department, and outpatient visits, respectively; all p < 0.01), and higher all-cause per patient per year costs (mean cost differences of $2090, $1606, and $483 for total, medical, and pharmacy costs, respectively; all p < 0.01). CONCLUSION: This study highlighted unmet needs in pediatric patients with CIU/CSU who had increased medication (e.g., oral corticosteroids) and HRU burden after a diagnosis for CIU/CSU, and higher rates of HRU and costs relative to those without CIU/CSU.

The burden of chronic spontaneous urticaria: unsatisfactory treatment and healthcare resource utilization in France (the ASSURE-CSU study).

Data on the clinical burden of chronic spontaneous urticaria (CSU) and economic consequences are lacking in France. To characterize the clinical and economic burden of CSU in symptomatic patients despite treatment by analysing data of French patients from the ASSURE-CSU study. ASSURE-CSU was an international observational study that included CSU patients with symptoms that lasted for 12 months or more despite treatment. Disease characteristics and healthcare resource use were obtained from medical records. Data on disease history, health-related quality of life (HR-QoL), and work productivity were collected from a patient survey. A total of 101 patients were analysed (76.2% female; mean age: 48.9 years) with moderate to severe disease (UAS7 score ≥16) in 43.4% and angioedema in 72.3%. The mean (S.D.) total scores of Chronic Urticaria Quality of Life (CU-Q2oL) and Dermatology Life Quality Index (DLQI) were 37.7 (22.3) and 9.7 (6.9), respectively, thus indicating a significant impact of the disease on HR-QoL. Mean absenteeism and presenteeism were 6.4% and 20.8%, respectively, with a mean loss of work productivity estimated at 20.7%. The mean (S.D.) total direct cost of CSU was €2,397 per patient per year and was mainly driven by therapies (€1,435) and inpatient costs (€859). The indirect costs for four weeks were mainly presenteeism (€421) and loss of work productivity (€420). CSU significantly impairs HR-QoL, which increases with the severity of the disease. The direct and indirect costs for the management of symptomatic CSU are an important economic burden.

Cost Utility of Omalizumab Compared with Standard of Care for the Treatment of Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) negatively impacts patient quality of life and productivity and is associated with considerable indirect costs to society. OBJECTIVE: The aim of this study was to assess the cost utility of add-on omalizumab treatment compared with standard of care (SOC) in moderate or severe CSU patients with inadequate response to SOC, from the UK societal perspective. METHODS: A Markov model was developed, consisting of health states based on Urticaria Activity Score over 7 days (UAS7) and additional states for relapse, spontaneous remission and death. Model cycle length was 4 weeks, and total model time horizon was 20 years in the base case. The model considered early discontinuation of non-responders (response: UAS7 ≤6) and retreatment upon relapse (relapse: UAS7 ≥16) for responders. Clinical and cost inputs were derived from omalizumab trials and published sources, and cost utility was expressed as incremental cost-effectiveness ratios (ICERs). Scenario analyses included no early discontinuation of non-responders and an altered definition of response (UAS7 <16). RESULTS: With a deterministic ICER of £3183 in the base case, omalizumab was associated with increased costs and benefits relative to SOC. Probabilistic sensitivity analysis supported this result. Productivity inputs were key model drivers, and individual scenarios without early discontinuation of non-responders and adjusted response definitions had little impact on results. ICERs were generally robust to changes in key model parameters and inputs. CONCLUSIONS: In this, the first economic evaluation of omalizumab in CSU from a UK societal perspective, omalizumab consistently represented a treatment option with societal benefit for CSU in the UK across a range of scenarios.

EQ-5D Utilities in Chronic Spontaneous/Idiopathic Urticaria.

OBJECTIVES: To obtain utility estimates suitable for use in economic models for chronic spontaneous (idiopathic) urticaria (CSU). METHODS: Patient-level data from three randomized clinical trials-ASTERIA I, ASTERIA II and GLACIAL-were analysed. Health states were derived from the Urticaria Activity Score over 7 days (UAS7); higher scores denote greater activity. The health state score ranges were urticaria free: 0; well-controlled urticaria: 1-6; mild urticaria: 7-15; moderate urticaria: 16-27; and severe urticaria: 28-42. The mean EQ-5D utilities were calculated for each health state. A mixed model was used to predict the EQ-5D according to UAS7 health states in a pooled data set containing all treatment arms and time points from the three trials. Pooled trial data were validated through visual comparisons and interaction terms. Fixed and random effects for trials and patients were included, along with the following covariates: UAS7 health state at baseline (moderate or severe); presence of angioedema at baseline and during follow-up; duration of CSU; number of previous CSU medications; visit; current treatment; and patient age and sex. RESULTS: There was a consistent improvement in EQ-5D utilities as urticaria activity decreased. The mean utilities ranged from 0.710 (severe urticaria) to 0.780 (moderate urticaria), 0.829 (mild urticaria), 0.862 (well-controlled urticaria) and 0.894 (urticaria free). Sensitivity and subgroup analyses confirmed the robustness of the results. CONCLUSION: The results suggest that EQ-5D utility scores increase with decreasing urticaria activity. EQ-5D utility scores enable the health-related quality of life of CSU patients to be compared with that of patients with other diseases.

The Impact of Chronic Urticaria from the Patient's Perspective: A Survey in Five European Countries.

BACKGROUND: Chronic spontaneous urticaria (CSU) is associated with considerable burden, but data from European patients are limited. METHODS: This study is a retrospective, cross-sectional analysis of National Health and Wellness Survey data from the five largest EU countries (5EU: France, Germany, Italy, Spain, and the UK) collected between 2010 and 2013. Burden of disease for patients with CSU was estimated by comparing individuals currently treated for chronic urticaria (proxy CSU cases) with controls selected from respondents without chronic urticaria. Matching and regression models were used to quantify the impact of chronic urticaria on health-related quality of life, self-reported psychological complaints, work and activity impairment, and healthcare use. RESULTS: The sample included 175,923 respondents. Prevalence of diagnosed chronic urticaria was 0.5 and 0.2% were treating the condition with a prescription. Cases (N = 369) had substantially lower (worse) regression-adjusted mean Mental Component Summary (40.2 vs. 45.4), Physical Component Summary (44.6 vs. 49.9), and SF-6D health utility scores (0.63 vs. 0.71; all p < 0.001) relative to controls (N = 1476), differences that exceed accepted minimally important differences for these measures. Depression, anxiety, and sleep difficulties were approximately twice as prevalent among those currently receiving treatment for chronic urticaria (all p < 0.001). Cases also had elevated presenteeism (31 vs. 17%), overall work impairment (37 vs. 20%), and impairment in non-work activities (42 vs. 26%; all p < 0.01) relative to controls. Physician visits (9.1 vs. 4.9), emergency room visits (0.8 vs. 0.3), and hospitalizations (0.3 vs. 0.2) were more frequent than in controls (all p < 0.01). CONCLUSIONS: This research adds to the existing evidence showing significant burden of CSU.

Effect of chronic urticaria on US patients: analysis of the National Health and Wellness Survey.

BACKGROUND: Chronic idiopathic (also called spontaneous) urticaria (CIU/CSU) is the most common form of chronic urticaria and has been associated with impairment to health outcomes, although the effect has never been assessed using a nationally representative sample in the United States. OBJECTIVES: To assess the burden of CIU/CSU from the patients' perspective in terms of health related quality of life, impairment to work and nonwork activities, and health care resource use. METHODS: Data were obtained from the US National Health and Wellness Survey. Current use of a prescription for the treatment of chronic hives was used as a proxy for CIU/CSU. Patients with CIU/CSU in the proxy group were matched 1:4 to respondents without chronic hives using survey year, sex, age, and race. Generalized linear models were adjusted for comorbidities, smoking, body mass index, and health insurance status. Outcome measures included the Medical Outcomes Study 12-Item and 36-Item Short Form Health Surveys; self-reported depression, anxiety, and sleep difficulties; the Work Productivity and Activity Impairment questionnaire, and health care resource use. RESULTS: After matching and adjustment for covariates, those currently using a prescription for chronic hives had mental component summary scores 5.7 points lower, physical component summary scores 6.5 points lower, and health utility scores 0.11 points lower than controls, as well as higher adjusted odds of reporting depression, anxiety, and sleep difficulties. Mean adjusted work impairment was approximately double in prescription-treated chronic hives relative to controls, as was frequency of health care visits. CONCLUSION: Chronic hives substantially affects quality of life, nonwork activities, capacity to work, and health care use, providing further evidence of a high burden of CIU/CSU across multiple health outcomes and unmet need for effective treatment.

Burden of Exacerbations in Patients with Moderate to Very Severe COPD in the Netherlands: A Real-life Study.

OBJECTIVE: The objective of this study was to compare rates of different types of acute exacerbations of COPD (AECOPDs) and healthcare utilization among patients with different severities of COPD. METHODS: Data for this study was obtained from the PHARMO Database Network, which includes drug dispensing records from pharmacies, hospitalization records and information from general practitioners. Patients with moderate to very severe COPD (GOLD II-III-IV) and a moderate or severe AECOPD between 2000 and 2010 were included in the study. Moderate and severe AECOPDs were defined by drug use and hospitalizations respectively. Study patients were followed from the first AECOPD to end of registration in PHARMO, death or end of study period, whichever occurred first. During follow-up, all recurrent AECOPDs were characterized and healthcare utilization was assessed. RESULTS: Of 886 patients in the study, 52% had GOLD-II, 34% GOLD-III and 14% had GOLD-IV. The overall AECOPD recurrence rate per person year (PY) increased from 0.63 for patients with GOLD-II to 1.09 for patients with GOLD-III and 1.33 for patients with GOLD-IV. The rate of severe AECOPD was 0.06, 0.14 and 0.17 per PY, respectively. CONCLUSION: AECOPD recurrence rates and healthcare utilization are significantly higher among patients with more severe COPD.

Quality of life and healthcare utilisation in cystic fibrosis: a multicentre study.

The aim of our study was to discover the health status and healthcare utilisation associated with pulmonary exacerbations in cystic fibrosis (CF) and chronic Pseudomonas aeruginosa infection. Patients with CF from five UK CF centres attended two visits, 8-12 weeks apart. They were classified at visit 1 as being in one of the three health states: no current pulmonary exacerbation; "mild" (no hospitalisation) pulmonary exacerbation; and "severe" (hospitalisation) pulmonary exacerbation. All patients completed the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and EuroQol (EQ-5D) and a clinical form, and forced expiratory volume in 1 s (FEV1) was measured at visits 1 and 2. Annual healthcare utilisation data were collected. 94 patients of mean±sd age 28.5±8.2 yrs and FEV1 58.7±26.8% were recruited. 60 patients had no pulmonary exacerbation, 15 had a mild and 19 had a severe pulmonary exacerbation at visit 1. EQ-5D and CFQ-R data showed that the worse the exacerbation, the poorer the health-related quality of life (HRQoL). There were strong relationships between the CFQ-R and EQ-5D domain scores. The mean rate of pulmonary exacerbations per patient per year was 3.6 (1.5 in hospital and 2.2 at home). The mean length of stay per hospital pulmonary exacerbation was 9 days. As exacerbation status worsens, patients experience worse HRQoL. There is a significant healthcare burden associated with treatment of pulmonary exacerbation and long-term prophylaxis.