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Background: Standardized measures for evaluating patients' experiences with nonalcoholic steatohepatitis (NASH) and their perceived changes with treatment in clinical trials have been limited. To meet this need, a patient-reported outcome (PRO) measure, NASH-CHECK, was developed to evaluate symptoms and health-related quality of life for patients with NASH. The objective of this study was to conduct a quantitative evaluation of the psychometric properties of NASH-CHECK. Methods: The study used data from a phase 2, randomized controlled trial of adult patients with NASH (NCT02855164). Analyses were conducted to determine the optimal scoring of NASH-CHECK and to evaluate reliability, construct validity, and ability to detect change in NASH-CHECK scale scores. Results: Data were available for 253 patients with NASH (61% female; mean [standard deviation] age = 53 [12] years). Following initial item-level analyses, including correlations and exploratory factor analysis, three items were removed from the measure. Confirmatory factor analysis supported the formation of four multi-item scales (Cognitive Symptoms, Activity Limitations, Social Impact, and Emotional Impact) and five single-item scales (Abdominal Pain, Abdominal Bloating, Fatigue, Sleep, and Itchy Skin). Psychometric analyses of the final NASH-CHECK scales provided support for their internal reliability, test–retest reliability, construct validity, and ability to detect change. Conclusion: The results support NASH-CHECK as a reliable, valid, and responsive measure to assess patients' perspectives of symptoms and the health-related quality of life impact of NASH in clinical trials and in routine practice. [ABSTRACT FROM AUTHOR]

This study investigated the association between urticaria activity and health-related quality of life (HRQoL). Patient evaluations from the ligelizumab Phase 2b clinical trial (N = 382) were pooled (NCT02477332). Daily patient diaries assessed urticaria activity, sleep and activity interference, the dermatology life quality index (DLQI), and work productivity and activity impairment-chronic urticaria (WPAI-CU). The number of DLQI scores, weekly sleep interference scores (SIS7), weekly activity interference scores (AIS7), and overall work impairment (OWI) evaluations with a complete response per weekly urticaria activity score (UAS7) using bands (0, 1–6, 7–15, 16–27, and 28–42) were reported. Over 50% of the patients had a mean DLQI of > 10 at baseline, indicating a significant effect of chronic spontaneous urticaria (CSU) on their HRQoL. Complete response (UAS7 = 0) evaluations corresponded with no impacts on other patient-reported outcomes. In total, 91.1% of UAS7 = 0 evaluations corresponded to DLQI scores of 0–1, 99.7% to SIS7 scores of 0, 99.7% to AIS7 scores of 0, and 85.3% to OWI scores of 0. This was significantly different compared with the UAS7 = 1–6 evaluations (61.9%, 68.5%, 67.7%, and 65.4%, respectively; p < 0.0001). Complete responses to treatment were associated with no impairments on the dermatology-QoL, no interferences with sleep and activity, and significantly improved capacities to work compared to patients who continued to have signs and symptoms, even for those with minimal disease activity. [ABSTRACT FROM AUTHOR]

The NASHmap model is a non-invasive tool using 14 variables (features) collected in standard clinical practice to classify patients as probable nonalcoholic steatohepatitis (NASH) or non-NASH, and here we have explored its performance and prediction accuracy. The National Institute of Diabetes and Digestive Kidney Diseases (NIDDK) NAFLD Adult Database and the Optum Electronic Health Record (EHR) were used for patient data. Model performance metrics were calculated from correct and incorrect classifications for 281 NIDDK (biopsy-confirmed NASH and non-NASH, with and without stratification by type 2 diabetes status) and 1,016 Optum (biopsy-confirmed NASH) patients. NASHmap sensitivity in NIDDK is 81%, with a slightly higher sensitivity in T2DM patients (86%) than non-T2DM patients (77%). NIDDK patients misclassified by NASHmap had mean feature values distinct from correctly predicted patients, particularly for aspartate transaminase (AST; 75.88 U/L true positive vs 34.94 U/L false negative), and alanine transaminase (ALT; 104.09 U/L vs 47.99 U/L). Sensitivity was slightly lower in Optum at 72%. In an undiagnosed Optum cohort at risk for NASH (n = 2.9 M), NASHmap predicted 31% of patients as NASH. This predicted NASH group had AST and ALT mean levels above normal range of 0–35 U/L, and 87% had HbA1C levels > 5.7%. Overall, NASHmap demonstrates good sensitivity in predicting NASH status in both datasets, and NASH patients misclassified as non-NASH by NASHmap have clinical profiles closer to non-NASH patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: The time required to reach clinical remission varies in patients with chronic urticaria (CU). The objective of this study is to develop a predictive model using a machine learning methodology to predict time to clinical remission for patients with CU. Methods: Adults with ≥ 2 ICD-9/10 relevant CU diagnosis codes/CU-related treatment > 6 weeks apart were identified in the Optum deidentified electronic health record dataset (January 2007 to June 2019). Clinical remission was defined as ≥ 12 months without CU diagnosis/CU-related treatment. A random survival forest was used to predict time from diagnosis to clinical remission for each patient based on clinical and demographic features available at diagnosis. Model performance was assessed using concordance, which indicates the degree of agreement between observed and predicted time to remission. To characterize clinically relevant groups, features were summarized among cohorts that were defined based on quartiles of predicted time to remission. Results: Among 112,443 patients, 73.5% reached clinical remission, with a median of 336 days from diagnosis. From 1876 initial features, 176 were retained in the final model, which predicted a median of 318 days to remission. The model showed good performance with a concordance of 0.62. Patients with predicted longer time to remission tended to be older with delayed CU diagnosis, and have more comorbidities, more laboratory tests, higher body mass index, and polypharmacy during the 12-month period before the first CU diagnosis. Conclusions: Applying machine learning to real-world data enabled accurate prediction of time to clinical remission and identified multiple relevant demographic and clinical variables with predictive value. Ongoing work aims to further validate and integrate these findings into clinical applications for CU management. [ABSTRACT FROM AUTHOR]

Background: Chronic spontaneous urticaria (CSU) negatively impacts patients' sleep, thereby reducing health‐related quality of life (HRQoL). Half of patients with inadequately controlled CSU report sleep interference often or every night, which can lead to depression, anxiety, social, and work‐related problems. Methods: This randomized, double‐blind, placebo‐controlled Phase 2b core study (NCT02477332) included adult patients ≥18 years with moderate to severe CSU inadequately controlled with H1‐antihistamines. The current analysis includes patients randomized to receive ligelizumab 72 or 240 mg, omalizumab 300 mg or placebo every 4 weeks (q4w) for five injections over 20 weeks with treatment‐free follow‐up for 24 weeks. Patients could enter the open‐label extension study (NCT02649218) from Week 32 onwards if their weekly urticaria activity score was ≥12, which included an open‐label treatment (52 weeks of ligelizumab 240 mg q4w) and a 48‐week post‐treatment follow‐up. Weekly Sleep Interference Scores (SIS7, range 0 [no interference]–21 [substantial interference]), Weekly Activity Interference Score (AIS7), Dermatology Life Quality Index (DLQI) scores, and Overall Work Impairment were assessed. Results: Mean baseline SIS7 scores were balanced between the treatment arms for ligelizumab 72 mg (n = 84) and 240 mg (n = 85), omalizumab 300 mg (n = 85), and placebo (n = 43). By Week 12, patients experienced large improvements in sleep interference, with least square mean (standard error) changes from baseline (CFB) in SIS7 of −7.84 (0.58), −7.55 (0.61), −6.98 (0.60), and −5.85 (0.81), respectively. By Week 12, CFB in AIS7 were −8.25 (0.57), −8.25 (0.59), −7.30 (0.60), and −5.62 (0.79), DLQI scores were −9.79 (0.77), −9.93 (0.81), −8.35 (0.79), and −6.99 (1.11), and Overall Work Impairment scores were −28.96 (3.73), −30.76 (3.71), −25.74 (3.91), and −20.13 (5.10) for ligelizumab 72 and 240 mg, omalizumab 300 mg and placebo, respectively. Improvements in each patient‐reported outcome were sustained with ligelizumab 240 mg treatment during the extension study. Conclusions: Ligelizumab showed effective and sustained responses in managing sleep interference in patients with CSU, and numerically higher responses than with omalizumab and placebo. Treating the symptoms of CSU with ligelizumab improved disease burden, HRQoL, and markedly improved sleep quality. [ABSTRACT FROM AUTHOR]

Introduction: Chronic spontaneous (previously known as idiopathic) urticaria (CSU) is a chronic skin disease with the potential for natural remission. The objectives of this targeted literature review were to identify evidence on the clinical course of CSU, including remission rates, and to estimate cumulative remission rates for different time points. Methods: Electronic databases (MEDLINE, MEDLINE-In Process, Embase, Web of Science, BIOSIS Previews and the Cochrane Library) and relevant conference proceedings were searched to identify studies involving patients with CSU aged ≥ 12 years that provide data on remission rates and disease duration. Observational studies with patient follow-ups of ≥ 1 year or review articles were included. Data extracted from five selected studies were used to run Kaplan–Meier (KM) analyses and best-fit distributions to calculate remission rates per 4-week period and weighted averages. Results: Ten publications were included in this review. The proportion of patients achieving remission within year 1 ranged from 21 to 47%, while reported remission rate estimates at year 5 were 34% and 45%. Based on calculated 4-weekly remission rates, cumulative remission estimates ranged from 9 to 38% at year 1, from 29 to 71% at year 5 and from 52 to 93% at year 20. Cumulative weighted average estimates for the proportion of patients remitting at years 1, 5 and 20 were 17%, 45% and 73%, respectively. Conclusions: Published evidence suggests that CSU is a self-limiting condition with variable disease severity and duration, apparently dependent on multiple factors. However, data sources differed in terms of definitions of disease severity and remission, as well as in conclusions on influencing factors. Further studies and uniform definitions are required. [ABSTRACT FROM AUTHOR]

Objective: To develop a computer model to predict patients with nonalcoholic steatohepatitis (NASH) using machine learning (ML).Materials and Methods: This retrospective study utilized two databases: a) the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) nonalcoholic fatty liver disease (NAFLD) adult database (2004-2009), and b) the Optum® de-identified Electronic Health Record dataset (2007-2018), a real-world dataset representative of common electronic health records in the United States. We developed an ML model to predict NASH, using confirmed NASH and non-NASH based on liver histology results in the NIDDK dataset to train the model.Results: Models were trained and tested on NIDDK NAFLD data (704 patients) and the best-performing models evaluated on Optum data (~3,000,000 patients). An eXtreme Gradient Boosting model (XGBoost) consisting of 14 features exhibited high performance as measured by area under the curve (0.82), sensitivity (81%), and precision (81%) in predicting NASH. Slightly reduced performance was observed with an abbreviated feature set of 5 variables (0.79, 80%, 80%, respectively). The full model demonstrated good performance (AUC 0.76) to predict NASH in Optum data.Discussion: The proposed model, named NASHmap, is the first ML model developed with confirmed NASH and non-NASH cases as determined through liver biopsy and validated on a large, real-world patient dataset. Both the 14 and 5-feature versions exhibit high performance.Conclusion: The NASHmap model is a convenient and high performing tool that could be used to identify patients likely to have NASH in clinical settings, allowing better patient management and optimal allocation of clinical resources. [ABSTRACT FROM AUTHOR]

The increasing prevalence and burden of nonalcoholic steatohepatitis (NASH) has spurred the development of new treatments and a need to consider outcomes used for NASH treatment decision making. Development of a NASH core outcome set (COS) can help prioritize outcomes of highest importance by incorporating the perspectives from a variety of decision makers. coreNASH was an initiative to develop a COS for NASH using a modified Delphi consensus process with a multi‐stakeholder voting panel. A candidate outcome list was created based on a literature review and key informant interviews. The candidate outcome list was then condensed and prioritized through three rounds of online voting and through discussion at an in‐person meeting. Outcomes were retained or eliminated based on predetermined consensus criteria, which included special weighting of patients' opinions in the first two voting rounds. The coreNASH Delphi panel included 53 participants (7 patients, 10 clinicians and researchers, 7 health technology assessors, 22 industry representatives, 2 regulators, and 5 payers) who considered outcomes for two NASH‐related COS: one for NASH without cirrhosis (F2‐F3) and one for NASH with cirrhosis (F4). The initial candidate outcome list for both disease stages included 86 outcomes. The panel agreed on including two core outcomes for NASH without cirrhosis and nine core outcomes for NASH with cirrhosis in the COS. Conclusion: A consensus‐based COS has been developed that can be used across the life cycle of NASH treatments. Outcomes included can contribute to decision making for regulatory, market access, and on‐market decision making. Including the coreNASH COS in clinical development programs will facilitate improved comparisons and help decision makers assess the value of new products. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Background: Data on the prevalence and disease management of chronic urticaria (CU) and chronic spontaneous urticaria (CSU) in the pediatric population are scarce. This study assessed the prevalence of CU and CSU, and disease management among pediatric patients (0‐17 years). Methods: A physician‐based online survey was conducted in 5 European countries (United Kingdom, Germany, Italy, France, and Spain) assessing the annual diagnosed prevalence, disease characteristics, and treatment patterns in the target population. Results are based on physician responses and analyzed using descriptive statistics. Prevalence estimates were calculated based on the number of CU/CSU pediatric patients diagnosed, seen, and treated by the respondents and extrapolated to the total pediatric population from each country. Results: Across 5 European countries, the one‐year diagnosed prevalence of CU and CSU in pediatric patients was 1.38% (95% CI, 0.94‐1.86) and 0.75% (95% CI, 0.44‐1.08), respectively. Angioedema was reported in 6%‐14% of patients. A large proportion of CSU pediatric patients (40%‐60%) were treated with H1‐antihistamines at approved dose and 16%‐51% received H1‐antihistamines at higher doses. Approximately 1/3 of pediatric CSU patients remained uncontrolled with H1‐antihistamines at approved/higher doses. Other prescribed treatments were oral corticosteroids (10%‐28%) and topical creams (15%‐26%). Conclusions: This study revealed a prevalence of CSU among pediatric population comparable to adults and also suggested an unmet need for approved treatments for inadequately controlled pediatric CSU patients. It is truly of concern that harmful (oral steroids) or insufficient (topical creams) treatments were frequently used despite better and guideline‐recommended alternatives. [ABSTRACT FROM AUTHOR]

Background The Urticaria Activity Score summed over 7 days (UAS7) assesses the itch severity and hive count in chronic spontaneous urticaria (CSU) using once- or twice-daily diary-based documentation. Objective The aim of this study was to evaluate the comparability of twice-daily versus once-daily versions of the UAS and the resulting UAS7 values. Methods Data came from the ASSURE-CSU study. The twice-daily and once-daily UAS7 was calculated from morning and evening ratings, as well as from exact 24-h evening ratings of hive count and itch severity, respectively. Three UAS7 scores were computed: UAS7 twice daily (UAS7TD), UAS7 once daily for maximum itch (UAS7OD1MAX), and UAS7 once daily for average itch (UAS7OD2AVG). UAS7 values were assigned to five score bands (0, 1-6, 7-15, 16-27, 28-42), reflecting urticaria-free to severe disease activity. The score values and score band ratios of the UAS7TD and UAS7OD versions were compared and assessed for correlation by weighted Cohen's kappa statistics. Results Data from 614 patients were analyzed. All three versions of the UAS7 yielded very similar results, with a mean (standard deviation) UAS7TD, UAS7OD1MAX, and UAS7OD2AVG of 17.3 (10.49), 17.7 (8.90), and 16.2 (8.68), respectively. Correlation coefficients between UAS7TD and UAS7OD1MAX, UAS7TD and UAS7OD2AVG, and UAS7OD1MAX and UAS7OD2AVG were 0.94, 0.95, and 0.99, respectively, showing very high positive pairwise correlation. The weighted kappa coefficient, ? (95% confidence interval) was 0.78 (0.75-0.82) for UAS7TD versus UAS7OD1MAX, and 0.82 (0.78-0.85) for UAS7TD versus UAS7OD2AVG, demonstrating substantial agreement. Conclusions The once- and twice-daily UAS7 scores were highly consistent, supporting the use of either version when evaluating CSU activity. [ABSTRACT FROM AUTHOR]

Introduction: Few studies have described chronic idiopathic/spontaneous urticaria (CIU/ CSU) healthcare burden in adults, while this information remains largely unknown in children. We aimed to describe treatment patterns, healthcare resource utilization (HRU), and costs in CIU/CSU pediatric patients, as well as to compare HRU and costs in CIU/CSU and CIU/ CSU-free pediatric patients. Methods: Medicaid claims from four states (09/ 01/2013–03/31/2016) were used to identify patients less than 12 years old. The CIU/CSU cohort included patients with either at least two claims for idiopathic, other, or unspecified urticaria at least 6 weeks apart, or at least one claim for urticaria and at least one claim for angioedema at least 6 weeks apart (index date defined as the first claim). The control cohort included patients without urticaria/angioedema claims (index date randomly assigned). Patients without at least 6 months of continuous Medicaid eligibility pre- and post-index were excluded. HRU and costs were compared between propensity score-matched cohorts during the post-index follow-up. Results: A total of 548 CIU/CSU patients (mean [SD] age 4.5 [3.3] years; 51.3% male) were matched 1:1 with controls. In the CIU/CSU cohort, 51.8% used non-sedating prescription H1-antihistamines, 24.3% used oral corticosteroids, and 23.5% used other prescription H1-antihistamines; 13.5% consulted allergist/immunologists and 2.4% consulted dermatologists in the first 6 months of follow-up. Compared to controls, CIU/CSU patients had significantly more per patient per year (PPPY) inpatient (incidence rate ratio [IRR] 2.05), outpatient (IRR 2.20), and emergency department (IRR 1.64) visits (all p values \0.05). Moreover, CIU/CSU patients also had significantly higher PPPY healthcare costs (mean cost difference [MCD] $1853), driven by incremental outpatient (MCD $1286) costs (all p values\0.01). Conclusions: CIU/CSU pediatric patients had low use of non-sedating H1-antihistamines and high use of oral corticosteroids. Compared to CIU/CSU-free controls in the same age group, CIU/CSU pediatric patients had higher HRU and healthcare costs. [ABSTRACT FROM AUTHOR]

Introduction: Chronic urticaria (CU), a proxy for chronic spontaneous urticaria, has been associated with a negative impact on health-related quality of life (HRQoL) and costs, but there is limited evidence on the burden of CU in Brazil. The objective of this study was to estimate the prevalence of CU and assess the burden of CU on HRQoL and healthcare resource utilization (HRU) among adults in Brazil. Methods: This retrospective, cross-sectional study, pooled data from the 2011, 2012, and 2015 National Health and Wellness Survey in Brazil (n = 36,000). Respondents (aged ≥18 years) diagnosed with and treated for CU provided data on demographics, health history, HRQoL (mental and physical health status) on Short-Form SF-36v2, presence of psychological complaints, work impairment, activity impairment, and HRU. Generalized linear models, controlling for covariates, examined differences between those treated for CU and matched controls on the outcome variables. Results: The prevalence of diagnosed CU was 0.41% (n = 249) and treated CU was 0.21% (n = 127). After adjustments, CU (currently treated for CU) was associated with worse mental functioning, physical functioning, and health utilities compared with controls (all p\0.01). CU had over twice the odds of anxiety and sleep difficulties, over 1.5 times the work and activity impairment, twice the number of total physician visits, eight times the number of allergist visits, and twice the number of emergency room visits as controls (all p<0.01). Conclusions: Many CU patients using prescription treatment experienced anxiety and sleep disturbances, poorer HRQoL, significant work and activity impairment, and high HRU, compared with matched general population controls. Findings suggest an unmet need for more effective treatment and management of CU in Brazil. Funding: Novartis Pharma AG and Genentech. [ABSTRACT FROM AUTHOR]

Purpose:Data are lacking on the burden of chronic idiopathic urticaria (CIU) versus other dermatologic conditions. This analysis compared the burden of chronic urticaria (CU, proxy for CIU) with psoriasis. Methods:Data from CU (N = 747) and psoriasis patients (N = 5107) came from 2010 to 2012 US National Health and Wellness Surveys. Outcomes included SF-12v2/SF-36v2 mental and physical component summary scores (MCS and PCS, respectively) and other health/activity-related measures. Results:MCS score was 44.7 for CU, and 48.2, 44.7 and 44.3 for mild/moderate/severe psoriasis, respectively (US norm = 50). PCS score was 43.8 for CU, and 46.5, 44.1 and 40.3 for mild/moderate/severe psoriasis. Health utility score was 0.67 for CU, and 0.72, 0.67 and 0.65 for mild/moderate/severe psoriasis. More CU patients reported depression (39%), anxiety (42%) and sleep difficulties (50%) than psoriasis patients (any severity). Overall work impairment was 29% for CU, and 19%, 26% and 31% for mild/moderate/severe psoriasis. Activities impairment was 39% for CU, and 28%, 37% and 43% for mild/moderate/severe psoriasis. CU and psoriasis patients had frequent healthcare visits. Conclusions:Patients with CU had impaired mental/physical health and work/non-work activities, similar to moderate-to-severe psoriasis patients. Results suggest that better disease management of CU is needed. This analysis should also reflect the significant burden of CIU. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) report difficulty with sleep. Methods: We examined the effect of omalizumab on sleep-related outcomes during 3-6 months omalizumab or placebo treatment and a 16-week follow-up period within three Phase III double-blind randomized placebocontrolled pivotal trials in CIU/CSU: ASTERIA I, ASTERIA II, and GLACIAL. Sleep quality was assessed in all three studies using sleep-related questions included in an electronic diary, the Chronic Urticaria Quality of Life Questionnaire, and the Medical Outcomes Study Sleep Scale. Score changes from baseline in the treatment arms were compared with that in the placebo arm and adjusted for baseline score and weight. We also examined correlations of sleep scores at baseline, week 12, and week 24 and the slopes of change between sleep and itch and hive. Results: Patients treated with omalizumab reported a larger reduction in sleep problems than those in the placebo arm; omalizumab 300 mg demonstrated the greatest improvement on all sleep components among all treatment arms. The largest reduction in sleep problems was reported within the first 4 weeks of therapy. After treatment discontinuation, sleep quality worsened. Sleep scores demonstrated moderate-to-strong correlation between them, and the change in sleep scores was associated with changes in itch and hives. Conclusions: Improvement in sleep was reported after the first dose of omalizumab. Sleep continued to improve throughout the active treatment period. Patients receiving omalizumab 300 mg achieved greater improvement in sleep than those in other treatment arms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Assessing the consequences of chronic spontaneous/idiopathic urticaria (CSU) requires the evaluation of health-related quality of life (HRQoL) associated with the severity of CSU signs and symptoms. It is important to understand how signs, symptoms, and HRQoL change over time in CSU. Evidence is lacking on how closely changes in signs and symptoms of CSU are related to changes in HRQoL. The objective of this study was to assess the correlation between changes in patient-reported outcome measures (PROMs) of signs and symptoms, dermatologic quality of life (QoL), and urticaria-specific QoL.Methods: Latent growth models (LGMs) were applied to longitudinal data from three randomized, Phase 3 clinical trials investigating the efficacy and safety of omalizumab in CSU.Results: A near-perfect association between changes in signs and symptoms and changes in dermatologic and urticaria-specific QoLs was identified in each clinical trial when using LGMs (correlation coefficient range 0.88-0.92).Conclusion: Evidence showed that changes in signs and symptoms are closely related to changes in HRQoL. However, analyses were performed on clinical trial results of an extremely effective treatment; a less effective treatment with much smaller changes over time may not show such close correlations. Results suggest that any of these PROMs may be used to understand changes in CSU. [ABSTRACT FROM AUTHOR]

Background Patients with chronic spontaneous urticaria ( CSU) are sometimes unresponsive to nonsedating, second-generation, H1 antihistamines; this study summarizes published clinical evidence for patients who remain symptomatic despite treatment. Objective To evaluate, via a systematic literature review, clinical evidence of management strategies for patients with CSU who remain symptomatic despite approved use of nonsedating H1 antihistamines. Methods Using a prespecified protocol, we searched MEDLINE, Embase, the Cochrane Library (1 January 1960-20 December 2011), and published conference abstracts (2010-2012). Rigorous criteria identified trials in patients with CSU who had a history of inadequate response to previous treatment or had used combination treatments. Trials evaluating treatment-naïve patients or first-line therapies were excluded. Results Qualitative data synthesized from 26 randomized, controlled trials, four prospective studies, and one retrospective study showed cyclosporine, desloratadine plus dapsone or dipyridamole, montelukast, and omalizumab reduced urticaria activity scores, weals, and pruritus, versus placebo. Optimal treatment doses and durations were unclear due to varying trial durations, outcome measurement scales, and assessment timings. No safety concerns were reported. Conclusions This review confirms that available evidence to guide treatment choice for patients with CSU with inadequate response to H1 antihistamines varies in quality. Further research is warranted due to low-quality trials with methodological and reporting limitations. [ABSTRACT FROM AUTHOR]

Background: Chronic spontaneous urticaria (CSU) formerly known as chronic idiopathic urticaria (CIU) is a severe and distressing skin condition that remains uncontrolled in approximately one half of patients, despite the use of licensed, recommended doses of modern, second-generation H1-antihistamines. So far, the humanistic, societal and economic burden of CSU/CIU has not been well quantified. Therefore it is important to broaden our understanding of how CSU/CIU impacts patients, society, and healthcare systems, by determining the disease burden of CSU/CIU and the associated unmet need; as well as to further guide the use of new treatments in an efficient and cost-effective manner. Methods: ASSURE-CSU is an observational, multicenter study being conducted in the UK, Germany, Canada, France, Italy, Spain, and The Netherlands. The study comprises a retrospective medical chart review in conjunction with patient surveys (including validated tools for assessment of disease impact) and an 8-day patient diary. The primary objectives of the study are to describe patient demographics, medical history, treatments, and healthcare resource utilization based on medical-record data and to assess the impact of disease, healthcare resource utilization, work days missed, and productivity loss based on patient-reported data. Approximately 700 patients (aged ≥18 years) will be enrolled who have CSU/CIU despite currently receiving treatment, and have had persistent symptoms for at least 12 months. Data will be collected retrospectively for the 12 months (±1 month) prior to enrolment wherever possible, and prospectively for the week following enrolment. Discussion: ASSURE-CSU will be the first study to examine the economic and humanistic burden of disease in patients diagnosed with CSU/CIU who are symptomatic despite treatment. By combining retrospective evaluation of medical records with prospective patient surveys and 8-day diaries, across seven different countries, the ASSURE-CSU study will contribute to a better understanding and acknowledgement of the burden of disease in patients with symptomatic chronic spontaneous urticaria. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To explore the published evidence on the link between treatment satisfaction and patients' compliance, adherence, and/or persistence. Methods: Articles published from January 2005 to November 2010 assessing compliance, adherence, or persistence and treatment satisfaction were identified through literature searches in Medline, Embase, and PsycInfo. Abstracts were reviewed by two independent researchers who selected articles for inclusion. The main attributes of each study examining the link between satisfaction and adherence, compliance, or persistence were summarized. Results: The database searches yielded 1278 references. Of the 281 abstracts that met the inclusion criteria, 20 articles were retained. In the articles, adherence and compliance were often used interchangeably and various methods were used to measure these concepts. All showed a positive association between treatment satisfaction and adherence, compliance, or persistence. Sixteen studies demonstrated a statistically significant link between satisfaction and compliance or persistence. Of these, ten demonstrated a significant link between satisfaction and compliance, two showed a significant link between satisfaction and persistence, and eight demonstrated a link between either a related aspect or a component of satisfaction (eg, treatment convenience) or adherence (eg, intention to persist). An equal number of studies aimed at explaining compliance or persistence according to treatment satisfaction (n = 8) and treatment satisfaction explained by compliance or persistence (n = 8). Four studies only reported correlation coefficients, with no hypothesis about the direction of the link. The methods used to evaluate the link were varied: two studies reported the link using descriptive statistics, such as percentages, and 18 used statistical tests, such as Spearman's correlation or logistic regressions. Conclusion: This review identified few studies that evaluate the statistical association between satisfaction and adherence, compliance, or persistence. The available data suggested that greater treatment satisfaction was associated with better compliance and improved persistence, and with lower regimen complexity or treatment burden. [ABSTRACT FROM AUTHOR]

Background: Phenotypic methods such as elevated liver tests and/or the presence of obesity or hypertension are often used to identify patients with T2DM at risk for NASH. Machine learning (ML) models allow the prediction of outcomes with many interacting features and may be superior to phenotype in the context of NASH and T2DM. Here we present an intergroup comparison between patients with T2DM predicted as positive or negative for NASH by NASHmap, a ML model showing high prediction performance in real-word datasets. Methods: We evaluated a subgroup of patients from a large T2DM clinical trial database (2002-2012) who had data for 14 NASHmap parameters. These include clinical observations and routine laboratory parameters but not HOMA-IR. We compared the profile of patients predicted by NASHmap (NASH positive or negative) using 17 parameters (14 NASHmap and 3 additional parameters). We compared HOMA-IR values between NASHmap positive and negative patients in the subgroup where the values were available. Results: The clinical database had 23038 metabolically compensated T2DM patients without chronic liver disease of other etiologies. Data for all 14 NASHmap parameters were available in 4336 patients. NASHmap positive patients were younger, had higher HbA1c, liver enzymes, triglycerides, WBC, body mass index, platelets, and a higher rate for hypertension. Data for HOMA-IR were available in 1208 patients. Median HOMA-IR value was 4.2 in NASHmap positive group vs. 2.6 in NASHmap negative group. Patients in both groups had a similar median duration of diabetes. Conclusion: Overall, the patients identified as at risk for NASH by NASHmap showed a metabolically unfavorable phenotype indicated by the higher HOMA-IR values in this group that the ML algorithm is also able to detect. ML models may be an important tool in effectively identifying patients at risk for NASH in electronic health records and clinical care. Disclosure: A. Tietz: Employee; Self; Novartis AG, Stock/Shareholder; Self; Novartis AG. G. Bader: Employee; Self; Novartis AG. M. Docherty: Employee; Self; ZS Associates. B. Reinhart: Employee; Self; ZS Associates. M. Balp: Employee; Self; Novartis AG. M. Pedrosa: Employee; Self; Novartis AG. S. K. Acharya: Employee; Self; Novartis Healthcare Pvt. Ltd., Employee; Spouse/Partner; Novartis Healthcare Pvt. Ltd. J. Loeffler: Employee; Self; Novartis AG, Stock/Shareholder; Self; Novartis AG. J. M. Schattenberg: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Consultant; Self; Boehringer Ingelheim, BMS, Echosens, Genfit, Gilead Sciences, Intercept Pharmaceuticals, Madrigal, Novartis, Novo Nordisk, Nordic Bioscience, Pfizer, Roche, Sanofi, Siemens Healthcare GmbH, Zydus, Bristol-Myers Squibb Company. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) and its progressive form nonalcoholic steatohepatitis (NASH) are under recognized due to low awareness and lack of specific symptoms. Machine learning techniques allow the creation of algorithms derived from large databases with many interacting features to predict outcomes of interest. The objective of this study was to estimate the patients who might have NASH in electronic health records (EHR) using a NASH machine learning model (NASHmap). Methods: NASHmap is a predictive extreme gradient boosting model built and validated in two databases in the USA. The model has a test area under the curve of 0.82 and 0.76 in the training and validation database, respectively. It uses 14 features, ranked by importance: HbA1c, AST, ALT, total protein, AST/ALT, BMI, triglycerides, height, platelets, WBC, hematocrit, albumin, hypertension, and gender. The model was applied to a cohort of patients in Optum EHR meeting predefined inclusion (e.g., common NASH comorbidities) and exclusion criteria (e.g., any other liver disease) and had the 14 features available. Results: Out of 86 million (M) patients in the Optum EHR, 14M met the inclusion and exclusion criteria and 3M had all 14 features. Among them ∼23,000 patients had a diagnosis of NASH or NAFLD based on ICD codes with 73% having type 2 diabetes (T2D), 65% female and 28% above 65 years. For the patients with no recorded NASH diagnoses, 56% had T2D, 54% were female and 46% were above 65 years. Among the 3M patients, NASHmap predicted ∼902,000 as potentially having NASH and among them 70% had T2D, 52% were female and 43% were above 65 years; median HbA1c was 7.1 for diabetics and 5.8 for nondiabetics. Conclusion: High-performing machine learning models can be used to alert on patients likely to have NASH. In clinical practice, this could help physicians to identify patients at risk and direct them to appropriate diagnostic and therapeutic interventions. Disclosure: M. Docherty: Consultant; Self; Novartis Pharmaceuticals Corporation. A. Tietz: Employee; Self; Novartis AG. Stock/Shareholder; Self; Novartis AG. S.A. Regnier: Employee; Self; Novartis AG. Stock/Shareholder; Self; Novartis AG. M. Balp: Employee; Self; Novartis AG. G. Capkun: Employee; Self; Novartis AG. J. Loeffler: Employee; Self; Novartis Pharmaceuticals Corporation. Stock/Shareholder; Self; Novartis Pharmaceuticals Corporation. M. Pedrosa: Employee; Self; Novartis AG. J.M. Schattenberg: Consultant; Self; GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Roche Foundation. [ABSTRACT FROM AUTHOR]