Disease burden and predictors associated with non-response to antihistamine-based therapy in chronic spontaneous urticaria.

Background: H1-antihistamines (H1AH) are the first-line treatment for chronic spontaneous urticaria (CSU), but 50% of patients have inadequate disease control at standard doses. Objective: To assess the comorbidity burden and healthcare resource utilization (HRU) associated with non-response to H1AH-based treatments; to identify predictors of non-response. Methods: Optum® de-identified Electronic Health Record dataset (2007-2020) was used to identify adult patients with CSU who initiated a H1AH, alone or in combination with other oral non-biologics (index treatment). Based on twelve-month treatment patterns observed after index treatment initiation, patients were categorized as responders (continued index treatment or had only 1 next H1AH treatment without corticosteroids) or non-responders (continued corticosteroids or had 2 or more treatment switches). Patient characteristics and HRU were assessed in the 12 months before (baseline) and ≥12 months after (follow-up) index treatment initiation. Baseline predictors associated with non-response were identified using machine learning. Results: There were 17 062 patients who met inclusion criteria, and 14824 (86.9%) were classified as non-responders. A higher proportion of non-responders had records of CSU-related symptoms, comorbidities, polypharmacy, and certain laboratory tests than responders at baseline. A higher proportion of non-responders than responders visited an allergist or dermatologist during follow-up (59.5% vs 53.0%). Non-responders had a larger increase in hospitalizations (15.7% vs -2.4%) than responders during follow-up vs baseline. Predictors of non-response included index and baseline treatment classes, types of specialists seen, chronic pulmonary disease, depression, and female sex. Conclusion: A large proportion of CSU patients treated with H1AH-based therapies had uncontrolled disease, contributing to increased HRU and patient burden. Non-responders had more comorbidities and HRU at baseline and follow-up, with steep increases in follow-up hospitalizations relative to baseline, highlighting an urgent need for early disease control.

Validation of NASH-CHECK: a novel patient-reported outcome measure for nonalcoholic steatohepatitis.

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.

Why a Complete Response Is the Treatment Aim in Chronic Spontaneous Urticaria.

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.

NASHmap: clinical utility of a machine learning model to identify patients at risk of NASH in real-world settings.

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.

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.

Ligelizumab improves angioedema, disease severity and quality-of-life in patients with chronic spontaneous urticaria.

Background: Disease burden is particularly high in Chronic Spontaneous Urticaria (CSU) patients with angioedema, and patients whose signs and symptoms are inadequately controlled by H1-antihistamines need new treatment options. Here we report an exploratory analysis, from the ligelizumab Phase 2b study, investigating angioedema occurrence in patients with CSU and describe the changes in angioedema following treatment with ligelizumab, omalizumab, or placebo. Methods: Data from the ligelizumab Phase 2b core (ligelizumab 72 mg, 240 mg, omalizumab 300 mg and placebo) and extension study (ligelizumab 240 mg) were used. Changes in Weekly Angioedema Activity Score (AAS7), the Dermatology Life Quality Index (DLQI), and Weekly Urticaria Activity Score (UAS7) among each time point were analyzed for each treatment arm. Results: From a total of 297 patients analyzed, 165 (55.6%) reported angioedema occurrence at baseline, with mean AAS7 ranging 30.6-42.2 across treatment arms. At Week 12 of the core study 87.5%, 84.6%, 75.0%, and 61.0% of patients were angioedema free for ligelizumab 72 mg, 240 mg, omalizumab 300 mg, and placebo arms, respectively. In CSU patients with angioedema at baseline, the largest change from baseline in AAS7 score was observed with ligelizumab 72 mg (-31.9) at week 16 in the core study. Patients with angioedema had a higher mean DLQI at baseline (14.9-16.1) vs. patients without angioedema (10.6-12.0). In patients with angioedema, low AAS7 was significantly associated with complete response on UAS7 (UAS7 = 0) and complete normalization of DLQI (DLQI 0-1). Conclusion: In the Phase 2b study, ligelizumab effectively reduced angioedema and urticaria symptoms, and improve health related quality of life in patients with moderate-to-severe CSU. Clinicaltrailsgov NCT number: NCT02477332; NCT02649218.

Predicting Clinical Remission of Chronic Urticaria Using Random Survival Forests: Machine Learning Applied to Real-World Data.

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.

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.

Ligelizumab improves sleep interference and disease burden in patients with chronic spontaneous urticaria.

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.

Clinical Remission of Chronic Spontaneous Urticaria (CSU): A Targeted Literature Review.

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.

Development of a novel machine learning model to predict presence of nonalcoholic steatohepatitis.

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.

Development of a Patient-Reported Outcome Measure for Non-Alcoholic Steatohepatitis (NASH-CHECK): Results of a Qualitative Study.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease characterized by excessive liver fat accumulation, inflammation, cell injury, and fibrosis. It is viewed as largely asymptomatic in its earlier (non-cirrhotic) stages, and information on the patient-perceived impact of NASH is scarce. OBJECTIVE: This study aimed to develop a NASH-specific patient-reported outcome (PRO) measure (NASH-CHECK) for use as a trial endpoint, using methods compliant with regulatory expectations. METHODS: A NASH conceptual model was developed based on the literature and clinical/patient expert review. The model guided concept elicitation (CE) interviews in patients with non-cirrhotic NASH recruited via a US tertiary care center. NASH-CHECK content was generated via thematic analysis of CE data and review by clinical/patient experts. Cognitive debriefing (CD) interviews with US patients evaluated content validity. RESULTS: The literature review confirmed that NASH impacts on functioning and health-related quality of life (HRQoL). Overall, 23 CE and 20 CD interviews were conducted. Key symptoms reported in CE interviews included pain in the upper-right abdomen (n = 14), fatigue (n = 18), poor sleep quality (n = 12), impaired memory (n = 13), and reduced focus (n = 11); key HRQoL impacts included impaired physical functioning, reduced ability to conduct daily living tasks, reduced quality of relationships, low mood, anxiety, and self-consciousness. The 52-item first-draft NASH-CHECK was reduced to 31 items based on patient feedback on item relevance, acceptability, and comprehension. CONCLUSIONS: The interviews revealed key symptoms and broad HRQoL impacts of NASH. As a disease-specific PRO measure assessing symptoms and HRQoL, the NASH-CHECK is relevant, comprehensive, and acceptable to patients and clinicians.

Real-World Burden of Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is associated with an increase in healthcare resource use and poor health-related quality of life (HRQoL). We assessed the humanistic and economic burden of NASH, disease management, and patient journey. METHODS: We performed a cross-sectional analysis of data, collected from July through November 2017, from the Growth from Knowledge Disease Atlas Real-World Evidence program, reported by physicians in United States, France, and Germany. We extracted demographic and medical data from medical records. Some patients voluntarily completed a survey that provided information on disease history, treatment satisfaction, and patient-reported outcomes. RESULTS: We analyzed data from 1216 patients (mean age, 54.9±12.3 years; 57.5% male; mean body mass index, 31.7±6.9); 64.6% had biopsy-confirmed NASH and comorbidities were recorded for 41.3%. Treatments included lifestyle modification (64.6%) or use of statins (25.0%), vitamin E (23.5%), or metformin (20.2%). Patients with biopsy-confirmed NASH reported more physician (4.5 vs 3.7) and outpatient visits (1.8 vs1.4) than patients with suspected NASH not confirmed by biopsy. Among the 299 patients who completed the survey, 47.8% reported various symptoms associated to their NASH. Symptomatic patients reported significantly lower HRQoL than patients without symptoms. CONCLUSIONS: In an analysis of data from 3 countries, we found NASH to be associated with regular use of medical resources; patients with symptoms of NASH had reduced HRQoL. The burden of NASH appears to be underestimated. Studies are needed to determine the burden of NASH by fibrosis stage and disease severity.

Health-related quality of life and patient-reported outcome measures in NASH-related cirrhosis.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is known to have a negative impact on patients' health-related quality of life (HRQoL), even before progression to cirrhosis has occurred. The burden of NASH-related cirrhosis from the patient perspective remains poorly understood. Herein, we aimed to identify the burden of disease and HRQoL impairment among patients with NASH-related compensated cirrhosis. METHODS: This targeted literature review sought first to identify the humanistic burden of disease from the perspective of patients with diagnosed NASH-cirrhosis and, secondly, to identify generic or disease-specific patient-reported outcome measures (PROMs) used to assess the impact of NASH-cirrhosis. Searches were conducted in bibliographical databases, grey or unpublished literature, liver disease websites, support group websites and online blogs. A quality assessment of specific PROMs was conducted. RESULTS: Patients with NASH-cirrhosis are reported to suffer from lower HRQoL than patients with non-cirrhotic NASH and the general population with respect to physical health/functioning, emotional health and worry, and mental health. Thirteen PROMs were identified, of which 4 were liver-disease specific: CLDQ, CLDQ-NAFLD, LDQoL and LDSI. The most commonly used measures do not comply with current industry or regulatory standards for PROMs and/or are not validated for use in a cirrhotic NASH population. CONCLUSIONS: Patients with NASH-cirrhosis have lower HRQoL and poorer physical health than patients with non-cirrhotic NASH. However, the literature lacked detail of the everyday impact on patients' lives. Currently, a number of PROMs are available to measure the impact of the disease in patients with chronic liver conditions. The lack of studies that include qualitative insights in this population mandates further exploration and research. LAY SUMMARY: It is not well understood how having non-alcoholic fatty liver disease (NAFLD)-related cirrhosis affects a person's everyday wellbeing and quality of life. Some research has been done with patients who have early stages of liver disease but not people with cirrhosis. We found that patients with NAFLD-related cirrhosis tended to have poorer health than patients without cirrhosis. But there was not very much information from patients themselves and there were no tools or questionnaires just for this group of patients.

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.

The Patient Perspectives on Future Therapeutic Options in NASH and Patient Needs.

Background: Non-alcoholic steatohepatitis (NASH) is a chronic liver disease with severe complications and without approved therapies. Currently, there is limited data on the overall burden of the disease for patients or on patient needs and preferences. This study investigates patient preferences in relation to potential future therapies for NASH. In addition, the factors that are relevant to patients and their importance in relation to future treatment options are explored. Method: Telephone in-depth interviews (TDIs) preceded an online 30-min quantitative survey. The online survey included (1) multiple choice questions (MCQs) on NASH diagnosis and disease background. (2) An exercise to determine patients' satisfaction levels with information provided at diagnosis, and to explore symptomatology in detail. (3) Exercises to evaluate potential new products and product attributes, including a "drag and drop" ranking exercise, and an adaptive choice-based conjoint exercise (ACBC). (4) The EQ-5D-5L questionnaire and the Visual Analog Scale (VAS), which measures patients' health status. (5) Collection of socio-demographic data, and (6) Questions to measure patient satisfaction with the survey. Results: There were 166 patients included in this study from Canada [n = 36], Germany [n = 50], the UK [n = 30], and USA [n = 50]. Fifty seven percent of patients [n = 94] had had a liver biopsy for confirmation of NASH. Patients were often unable to link their symptoms to NASH or other conditions. ACBC results showed that efficacy, defined as "impact on liver status" was the single most important attribute of a potential future NASH therapy. Other attributes considered to have secondary importance included impact on weight, symptom control and the presence of side effects. The EQ-5D utility score was 0.81 and VAS = 67.2. Conclusion: "Impact on liver status" is the primary outcome sought. Patients demonstrate a general lack of understanding of their disease and appeared to be unfamiliar with longer-term consequences of NASH. It is necessary to improve patient understanding of NASH and its progressive nature, and there is a need for improving confirmatory diagnosis and monitoring.

The burden of non-alcoholic steatohepatitis (NASH) among patients from Europe: A real-world patient-reported outcomes study.

Data on the economic and humanistic burden of non-alcoholic steatohepatitis (NASH) are scarce. This study assessed the comparative burden of NASH, relative to a representative sample from the general population and a type 2 diabetes mellitus (T2DM) cohort, in terms of health-related quality of life, work productivity and activity impairment (WPAI), and healthcare resource use. METHODS: Data across 5 European countries came from the 2016 National Health and Wellness Survey, a nationally representative patient-reported outcomes survey. Outcomes included mental (MCS) and physical (PCS) component scores from the Short-Form (SF)-36v2, WPAI scores, self-reported physician diagnosis of sleep difficulties, anxiety, and depression, and healthcare resource use: healthcare professional visits, hospital visits, and emergency room visits in the previous 6 months. Bivariate and multivariable analyses were conducted for each outcome and comparative group. RESULTS: After adjusting for matching criteria and covariates, patients with NASH (n = 184) reported significantly worse health-related quality of life, worse WPAI scores, and more healthcare resource use than the general population (n = 736) (MCS 39.22 vs. 45.16, PCS 42.84 vs. 47.76; overall work impairment 49.15% vs. 30.77%, healthcare professional visits 10.73 vs. 6.01, emergency room visits 0.57 vs. 0.22, hospitalizations 0.47 vs. 0.17, p ≪0.05 for all). Patients with NASH did not differ from patients with T2DM (n = 368) on PCS and WPAI scores, suggesting a similar impairment on work and daily activities, but did report significantly worse mental status (MCS 39.64 vs. 43.64, p ≪0.05) and more healthcare resource use than those with T2DM (healthcare professional visits 10.85 vs. 7.86, emergency room visits 0.65 vs. 0.23, hospitalizations 0.39 vs. 0.19, p ≪0.05 for all). CONCLUSIONS: These findings suggest that the burden of NASH may be underestimated, highlighting the unmet needs of patients with NASH. LAY SUMMARY: These findings show that patients with non-alcoholic steatohepatitis (NASH) experience a significant burden of illness, in terms of health-related quality of life, work productivity and activity impairment, and healthcare resource use. As there is currently no approved treatment for NASH, these findings highlight the unmet medical need of patients with NASH.

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.

Prevalence and clinical characteristics of chronic spontaneous urticaria in pediatric patients.

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.