Public Health Impact and Cost-Effectiveness of Empagliflozin (JARDIANCE®) in the Treatment of Patients with Heart Failure with Preserved Ejection Fraction in France, Based on the EMPEROR-Preserved Clinical Trial.

INTRODUCTION: The efficacy and safety of empagliflozin in the treatment of heart failure with preserved ejection fraction (HFpEF) were demonstrated in the EMPEROR-Preserved trial, which showed a 21% reduction in combined risks of cardiovascular death or HF hospitalization [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69-0.90, p < 0.001] and a 27% reduction in the total number of HF hospitalizations (HR 0.73; 95% CI 0.61-0.88, p < 0.001) compared with placebo. On the basis of these results, the present study aimed to assess the cost-effectiveness of empagliflozin + standard of care (SoC) compared with SoC alone in the treatment of HFpEF. METHODS: A published Markov model was adapted to compare the health and economic outcomes in France, considering a collective perspective, in patients treated with empagliflozin in addition to SoC versus patients treated by SoC alone. The model simulated the intention-to-treat (ITT) population of the trial, transitioning between four mutually exclusive health states representing the quartiles of the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). For each arm, the model estimated (over a lifetime time horizon) the economics and the health outcomes (HF hospitalizations avoided, and life years and quality-adjusted life years (QALYs) gained) to calculate the incremental cost-effectiveness ratios (ICERs). The resources used were derived by pairing the FREnch Survey on HF (FRESH) cohort data to French health insurance claims data, and the utilities were derived on the basis of the EQ-5D-5L questionnaire valued on the French tariff. Both economic and health outcomes were discounted at a 2.5% annual rate. RESULTS: The model predicted that treatment of HFpEF patients with empagliflozin would prevent, for 1000 patients treated, 74 HF hospitalizations and 15 deaths attributable to cardiovascular events, resulting on average in a gain of 1 month in overall survival (7.24 versus 7.16 years with placebo) and 0.11 QALYs (6.14 versus 6.03 with placebo). Empagliflozin costs were partially offset by the cost savings from avoided hospitalizations. The ICERs were €18,597 per life year gained and €13,980 per QALY gained. The sensitivity analyses conducted showed that empagliflozin has a 65% probability to be cost-effective under the €25,000/QALY threshold. CONCLUSIONS: The base-case results showed that empagliflozin is a cost-effective strategy for management of HFpEF, in addition to the impact on public health by preventing HF-hospitalizations and deaths in France. Sensitivity analyses suggest that 65% of simulations are under the €25,000/QALY threshold.

Hospital Resource Utilization and Costs in Patients with Heart Failure in France.

BACKGROUND AND OBJECTIVES: Heart failure (HF) is one of the leading causes of morbidity and mortality, and economic burden on the healthcare system. The aim of this study was to estimate the current hospital resource utilization and costs for HF patients in France. METHODS: This retrospective cohort study included adult HF patients hospitalized in France between January 1, 2019 and December 31, 2019. Data related to sociodemographic characteristics, number and duration of hospital stays, use of medical procedures or expensive and innovative drugs/medical devices included in the "liste-en-sus", and comorbidities were retrieved from the French national hospital discharge database. Data were further stratified based on the presence or absence of cardiac decompensation, comorbidities, ejection fraction (EF) status, and incident/prevalent patients. RESULTS: In 2019, a total of 430,544 patients were hospitalized in France with HF as a primary or associated diagnosis, with 51.9% male and 48.1% female and a mean age of 79.0 years. More than 75% of the study population was composed of prevalent HF patients. About 3.1% of patients were diagnosed with at least one event of cardiac decompensation during follow-up. Also, 20.2% and 9.9% of patients were identified with preserved and reduced EFs, respectively. The average number and length of hospital stays were 1.7 per patient and 10.4 days per patient, respectively. The annual cost of hospitalization for HF was €8341.3 per patient. Presence of cardiac decompensation at index date or during follow-up, reduced EF, and comorbidities were associated with numerically higher frequency and length of hospitalization, and hospitalization cost. For hospitalization and 'liste-en-sus' medical devices, higher cost was observed in incident than prevalent HF patients, while for 'liste-en-sus' drugs, higher cost was reported in prevalent than incident HF patients. CONCLUSION: This study highlighted the high economic hospital burden of HF in France. More studies investigating different HF patient profiles must be conducted to help determine the main factors of hospital cost for HF.

Quality of life in SSc-ILD patients: Understanding the impact of the ILD and the needs of the SSc-ILD patients and their need for caregivers in France.

Objectives: The objectives of this study were to describe the impact of systemic sclerosis associated interstitial lung disease, on quality of life, to estimate the correlation between quality of life and severity of lung disease and to assess the impact of interstitial lung disease on caregivers. Methods: Seven investigators included systemic sclerosis associated interstitial lung disease patients from December 2019 to April 2020. Sociodemographics and clinical data were collected. Patients reported outcomes and questionnaires were used with 1 generic patients reported outcome (EQ-5D-5L), 1 specific PRO (Brief Interstitial Lung Disease) and 2 self-reported questionnaires on impact of SSc complications and impact on caregivers. The correlation between forced vital capacity and EQ-5D-5L score was estimated with a multivariate linear regression model adjusted on several covariates. Results: In all, 89 patients were included. 26.4% were males, mean age was 58.2 ± 14.5 years. Mean EQ-5D-5L score = 0.79 ± 0.22 (median = 0.85). Mean EQ-5D-5L visual analog scale score = 60.8 ± 20.4 (median = 61.5). Mean King's Brief Interstitial Lung Disease score = 58.4 ± 12.7 (median = 58.0). After adjustment on covariates, a significant correlation between forced vital capacity and EQ-5D-5L score was found with an increase of 0.003 of the EQ-5D-5L score for a 1% increase of FVC (p = 0.0096). No significant correlation between forced vital capacity and the EQ-VAS and King's Brief Interstitial Lung Disease score were found. The impact of SSc on other organs was significantly correlated with EQ- 5D-5L score, respectively, for the impact scores on the lung system (p = 0.0003), heart system (p = 0.0182), Raynaud's syndrome (p = 0.0015), digestive system (p = 0.0032), joints/muscles (p = 0.0003), skin (p < 0.0001), kidney (p = 0.0052) and gastro-oesophageal reflux (p = 0.0063). Significant correlations between King's Brief Interstitial Lung Disease score and lung system (p < 0.0001), heart system (p < 0.0001), digital ulcers (p = 0.058), digestive system (p < 0.0001), kidney (p = 0.0004), skin (p = 0.0499) and gastro-oesophageal reflux (p = 0.0033) scores were found 68.5% of patients reported their need for a caregiver to help them in their daily life activities. Conclusion: Our study highlighted the strong burden of systemic sclerosis associated interstitial lung disease` for patients, especially with an impact on quality of life, on other organs manifestations and need for caregivers in their daily life.

Epidemiology, Mortality and Healthcare Resource Utilization Associated With Systemic Sclerosis-Associated Interstitial Lung Disease in France.

Objectives: To investigate the clinical characteristics, epidemiology, survival estimates and healthcare resource utilization and associated costs in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) in France. Methods: The French national administrative healthcare database, the Système National des Données de Santé (SNDS), includes data on 98.8% of the French population, including data relating to ambulatory care, hospitalizations and death. In our study, claims data from the SNDS were used to identify adult patients with SSc-ILD between 2010 and 2017. We collected data on clinical features, incidence, prevalence, survival estimates, healthcare resource use and costs. Results: In total, 3,333 patients with SSc-ILD were identified, 76% of whom were female. Patients had a mean age [standard deviation (SD)] of 60.6 (14.4) years and a mean (SD) individual study duration of 3.9 (2.7) years. In 2016, the estimated overall incidence and prevalence were 0.69/100,000 individuals and 5.70/100,000 individuals, respectively. The overall survival estimates of patients using Kaplan-Meier estimation were 93, 82, and 55% at 1, 3, and 8 years, respectively. During the study, 98.7% of patients had ≥1 hospitalization and 22.3% of patients were hospitalized in an intensive care unit. The total annual mean healthcare cost per patient with SSc-ILD was €25,753, of which €21,539 was related to hospitalizations. Conclusions: This large, real-world longitudinal study provides important insights into the epidemiology of SSc-ILD in France and shows that the disease is associated with high mortality, healthcare resource utilization and costs. SSc-ILD represents a high burden on both patients and healthcare services. Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03858842.

Functional impairment in patients with major depressive disorder: the 2-year PERFORM study.

BACKGROUND: The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study describes the course of depressive symptoms, perceived cognitive symptoms, and functional impairment over 2 years in outpatients with major depressive disorder (MDD) and investigates the patient-related factors associated with functional impairment. METHODS: This was a 2-year observational study in 1,159 outpatients with MDD aged 18-65 years who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Functional impairment was assessed by the Sheehan Disability Scale and the Work Productivity and Activity Impairment questionnaire. Patients assessed depression severity using the nine-item Patient Health Questionnaire and severity of perceived cognitive symptoms using the five-item Perceived Deficit Questionnaire. To investigate which patient-related factors were associated with functional impairment, univariate analyses of variance were performed to identify relevant factors that were then included in multivariate analyses of covariance at baseline, month 2, months 6 and 12 combined, and months 18 and 24 combined. RESULTS: The greatest improvement in depressive symptoms, perceived cognitive symptoms, and functional impairment was seen immediately (within 2 months) following initiation or switch of antidepressant therapy, followed by more gradual improvement and long-term stabilization. Improvement in perceived cognitive symptoms was less marked than improvement in depressive symptoms during the acute treatment phase. Functional impairment in patients with MDD was not only associated with severity of depressive symptoms but also independently associated with severity of perceived cognitive symptoms when adjusted for depression severity throughout the 2 years of follow-up. CONCLUSION: These findings highlight the burden of functional impairment in MDD and the importance of recognizing and managing cognitive symptoms in daily practice.

A clinical research practice datalink analysis of antidepressant treatment patterns and health care costs in generalized anxiety disorder.

OBJECTIVE: To describe real-life prescription patterns, health care resource use, and costs in adults with generalized anxiety disorder (GAD) initiating antidepressant (AD) treatment in the United Kingdom. METHODS: A retrospective longitudinal cohort study using data from Clinical Research Practice Datalink was conducted. Adults with incident prescription of an AD (index date) between January 1, 2006, and June 30, 2010, and with a diagnosis of GAD within the 2 months preceding or following the index date were included. Patients with a diagnosis of schizophrenia or bipolar disorder were excluded. RESULTS: A total of 29,131 patients with GAD were included in the analysis. Their mean age was 48.5 ± 15.5 years, and two thirds were women. GAD-licensed ADs (i.e., escitalopram, paroxetine, venlafaxine XR, and duloxetine) represented only 12.5% of the index AD prescriptions. At least one anxiolytic was prescribed for 23.5% of the patients. Only 33.2% of the patients continued index AD treatment over the study period. Discontinuation occurred for 46.0% of the patients, after a mean of 3.7 months of treatment. The health care costs were £338.4 per patient in the 6 months before the index date and £984.6 in the 9 months after the index date. Psychiatric hospitalization (relative risk = 4.18; 95% CI 3.53-4.96; P < 0.001) and duloxetine as index treatment (relative risk = 1.85; 95% CI 1.30-2.63; P < 0.001) were the main determinants of increased costs for these patients. CONCLUSIONS: The significant rate of AD discontinuation and associated treatment duration indicate unmet needs among patients with GAD. As described in American studies, substantial health care costs were also observed in this study.

Pattern and predictors of sick leave among users of antidepressants: a Danish retrospective register-based cohort study.

OBJECTIVES: Depression is associated with work absenteeism, reduced productivity, and significant personal and societal economic burden. We describe patterns and determinants of sick leave among working Danish antidepressant users. METHODS: Persons starting antidepressant treatment (January 1, 2004 through December 31, 2005) were identified from a representative 25% sample of the Danish population by linking Danish national registries. Inclusion criteria were age 18-64 years, being in the workforce the week prior to the first antidepressant prescription (index prescription, IP), and no antidepressant prescription in the year prior to the IP. Only sick leaves >2 weeks are centrally registered in Denmark and could be assessed. Cox regression analyses identified predictors of sick leave during the year following the IP, based on previous history of sick leave and clinical and socio-demographic baseline characteristics. RESULTS: In the cohort of 25,908 (59.7% women), sick leave prevalence increased from 37.5% (year prior to IP) to 45.3% (year after the IP); 30.7% were on sick leave for >8 weeks. Incidence peaked (35.5% of individuals) the week after the IP. Of persons with sick leave in the year before the IP, 62.7% were on sick leave the first week after the IP, vs 5.7% of those without previous sick leave. Predictors associated with increased risk of sick leave among those without previous sick leave were unemployment, female gender, age 25-54 years, couples with children, and vocational and higher intermediate education (including e.g. teachers and nurses). LIMITATIONS: Reasons for sick leave, sick leaves of less than 14 days and the indications for antidepressant treatment were unknown. CONCLUSIONS: Sick leave was prevalent in persons starting new antidepressant use, often lasting >8 weeks. Previous sick leave was the strongest predictor of subsequent sick leave.