The Lifetime Burden of Schizophrenia as Estimated by a Government-Centric Fiscal Analytic Framework.

Objective: To estimate the fiscal consequences of schizophrenia compared to the general US population using a "government perspective" fiscal analytic modeling framework capturing lost tax revenue and broader government costs in 2021.Methods: Schizophrenia was modeled from age 23 using a cohort-based Markov chain with 6-week cycles, simulating the effect of antipsychotic treatment sequences on remission and relapse. Markov states were defined using efficacy and safety outcomes from short- and long-term clinical trials. Mortality was based on US lifetables, schizophrenia-related suicide, and cardiovascular risks. A semi-Markov model with annual cycles simulated the likelihood and costs of incarceration and homelessness in community-based individuals. Lifetime fiscal consequences were estimated conditionally to survival, remission/relapse status, and likelihood of socioeconomic outcomes. Costs and life years were discounted at 3.0% annually. Uncertainty was explored in 1-way and scenario analyses.Results: Unemployment, disability, incarceration, homelessness, health care use, and productivity losses were more common in people living with schizophrenia. Schizophrenia was associated with a $1,540,042 per person lifetime fiscal loss to the government, with $56,707 per life year lived with schizophrenia. Health care costs represented 41.9% of the fiscal losses, 39.4% were due to criminal and homelessness costs, and 17.5% related to foregone tax revenue. Considering a 1.19% prevalence of schizophrenia, the estimated annual fiscal burden in the US was $173.6 billion.Conclusions: The fiscal framework illustrates how schizophrenia influences taxation and government transfer payments over time. These findings can be used to augment cost-effectiveness analyses and inform stakeholders of the fiscal impact of schizophrenia to inform priority interventions.

Comparative economic outcomes in patients with focal seizures initiating eslicarbazepine acetate versus brivaracetam in the long-term care setting in the USA.

Aim: To compare all-cause and epilepsy-specific pharmacy and total costs associated with initiation of eslicarbazepine acetate (ESL) or brivaracetam (BRV) among patients with focal seizures in long-term care (LTC) in the US. Methods: This retrospective analysis used data from IQVIA's New Data Warehouse. Results: 298 patients initiated ESL and 282 patients initiated BRV. Initiation of ESL versus BRV was associated with 33.3% lower all-cause pharmacy costs, 34.4% lower epilepsy-specific pharmacy costs, 21.3% lower all-cause total costs and 30.9% lower epilepsy-specific total costs (all p < 0.0001). Conclusion: Among patients with focal seizures in LTC in the US, initiation of ESL versus BRV was associated with significant reductions in all-cause and epilepsy-specific pharmacy and total costs compared with initiation of BRV.

The Economic Burden of Schizophrenia in the United States.

Aim: The economic burden of schizophrenia in the United States (US) was estimated at $155.7 billion in 2013. Since 2013, the US experienced significant health care reforms and treatment advances. This study analyzed recent data and literature to update the US economic burden estimate for schizophrenia.Methods: Direct and indirect costs associated with schizophrenia were estimated using a prevalence-based approach. Direct health care costs were assessed retrospectively using an exact matched cohort design in the IBM Watson Health MarketScan databases from October 1, 2015, through December 31, 2019. Patients with schizophrenia (identified using ICD-10-CM codes F20 and F25) were exactly matched to controls on demographics, insurance type, and index year. Direct non-health care costs were estimated using published literature and government data. Indirect costs were estimated using a human capital approach and the value of quality-adjusted life-years lost. Cost offsets were estimated to account for basic living costs avoided. Excess costs, comparing costs for individuals with and without schizophrenia, were reported in 2019 USD.Results: The estimated excess economic burden of schizophrenia in the US in 2019 was $343.2 billion, including $251.9 billion in indirect costs (73.4%), $62.3 billion in direct health care costs (18.2%), and $35.0 billion in direct non-health care costs (10.2%). The largest drivers of indirect costs were caregiving ($112.3 billion), premature mortality ($77.9 billion), and unemployment ($54.2 billion). Cost offsets, representing $6.0 billion (1.7%), were subtracted from direct non-health care costs.Conclusions: The estimated burden of schizophrenia in the US doubled between 2013 and 2019 and was $343.2 billion in 2019, highlighting the importance of effective strategies and treatment options to improve the management of this difficult-to-treat patient population.

Burden of EPS in commercial patients with schizophrenia initiating atypical antipsychotics.

OBJECTIVES: Extrapyramidal symptoms (EPS) affect 15% to 30% of patients with schizophrenia treated with antipsychotics and have been associated with poor outcomes. This study examined the incidence and economic burden of EPS in patients with schizophrenia initiating atypical antipsychotics (AAPs). STUDY DESIGN: Retrospective analysis of secondary deidentified administrative claims database. METHODS: Patients with schizophrenia initiating AAPs with no prior EPS were identified in the MarketScan Commercial and Medicare Supplemental databases from January 1, 2012, to December 31, 2018. Incidence of EPS (diagnosis or medication use) was assessed in the year following AAP initiation. Annual all-cause and schizophrenia-related health care resource utilization (HCRU) and costs were assessed in cohorts who did or did not develop EPS in the year following first EPS claim (EPS cohort) or randomly assigned index date (non-EPS cohort). Multivariate regression was used to compare all-cause and schizophrenia-related total health care costs and inpatient admissions between cohorts. RESULTS: A total of 3558 patients with schizophrenia newly initiating AAPs were identified; 22.1% developed EPS in the year following AAP initiation (incidence: 26.9 cases per 100 person-years). Multivariate analyses revealed that patients with EPS had 34% higher odds of all-cause (odds ratio [OR], 1.3361; 95% CI, 1.0770-1.6575; P < .01) and 84% increased odds of schizophrenia-related (OR, 1.8436; 95% CI, 1.0434-2.4219; P < .0001) inpatient admission compared with the non-EPS cohort. The EPS cohort also evidenced significantly higher adjusted all-cause ($26,632 vs $21,273; P < .001) and schizophrenia-related ($9018 vs $4475; P < .0001) costs compared with the non-EPS cohort. CONCLUSIONS: The 20% of patients who developed EPS in the year following AAP initiation evidenced significantly increased HCRU and costs over the postindex period. Schizophrenia therapies with reduced EPS risk are needed to improve patient care.

Healthcare resource utilization and quality of life by cognitive impairment in patients with schizophrenia.

OBJECTIVE: The objective was to investigate the association between cognitive impairment and healthcare resource utilization (HCRU) and quality of life (QoL) among patients with schizophrenia. METHODS: Data from the Adelphi Schizophrenia Disease Specific Programme™, a point-in-time survey of physicians and their patients, were collected in the United States between July-October 2019. Psychiatrists reported on patient cognitive function, HCRU, housing circumstances and employment status for their next 10 consulting adult patients with schizophrenia. Patients were classified as having no/mild or moderate/severe cognitive impairment and asked to complete a QoL questionnaire voluntarily. Multiple regression analysis estimated the association between severity of cognitive impairment and patient outcomes adjusting for patient demographics and clinical characteristics. RESULTS: Psychiatrists (n=124) reported on 651 and 484 patients with no/mild and moderate/severe cognitive impairment, respectively. Moderate/severe vs. no/mild cognitive impairment was associated with greater odds of hospitalization related to schizophrenia relapse within the last 12 months (adjusted odds ratio [aOR] [95% CI] = 2.23 [1.53-3.24]) and being unemployed due to disability (aOR = 2.39 [1.65-3.45]). Patients with moderate/severe vs. no/mild cognitive impairment had worse average QoL (EuroQoL 5-dimension [EQ-5D] Health Index: difference = -0.09 [-0.13 to -0.04]; EQ-5D Visual Analogue Scale: difference = -7.0 [-13.0 to -1.0]) and overall life satisfaction (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form: difference = -8.4 [-14.1 to -2.8]). CONCLUSIONS: Moderate/severe cognitive impairment among patients with schizophrenia was associated with worse patient outcomes including greater risk of hospitalizations related to schizophrenia relapse. Treatment to improve cognitive function could benefit the large proportion of patients with schizophrenia who suffer from cognitive impairment.

Indirect comparison of apomorphine sublingual film and levodopa inhalation powder for Parkinson's disease 'OFF' episodes.

Aim: To compare efficacy of apomorphine sublingual film (APL) and levodopa inhalation powder (CVT-301) for 'on-demand' treatment of Parkinson's disease 'OFF' episodes. Patients & methods: Patient-level data from an APL pivotal study were re-weighted to match average baseline characteristics from a CVT-301 study (SPAN-PD). Placebo-adjusted treatments were compared at week 12. Results: Improvements in predose Unified Parkinson's Disease Rating Scale Part III scores were significantly larger for APL versus CVT-301 at 60 min postdose (least squares mean difference-in-difference: -8.82; p = 0.002); difference at 30 min favored APL but was not statistically significant (-4.46; p = 0.103). Total daily 'OFF' time reductions were significantly larger for APL versus CVT-301 (-1.31 h; p = 0.013). Conclusion: Results suggest APL treatment may lead to improved efficacy versus CVT-301.

Development of MDS-Based Predication Model for COPD Severity in Nursing Home Residents.

BACKGROUND: Assessing chronic obstructive pulmonary disease (COPD) severity is challenging in nursing home (NH) residents due to incomplete symptom assessments and exacerbation history. OBJECTIVE: The objective of this study was to predict COPD severity in NH residents using the Minimum Data Set (MDS), a clinical assessment of functional capabilities and health needs. METHODS: A cohort analysis of prospectively collected longitudinal data was conducted. Residents from geographically varied Medicare-certified NHs with age ≥60 years, COPD diagnosis, and ≥6 months NH residence at enrollment were included. Residents with severe cognitive impairment were excluded. Demographic characteristics, medical history, and MDS variables were extracted from medical records. The care provider-completed COPD Assessment Test (CAT) and COPD exacerbation history were used to categorize residents by Global Initiative for Chronic Lung Disease (GOLD) A to D groups. Multivariate multinomial logit models mapped the MDS to GOLD A to D groups with stepwise selection of variables. RESULTS: Nursing home residents (N = 175) were 64% women and had a mean age of 77.9 years. Among residents, GOLD B was most common (A = 13.1%; B = 44.0%; C = 5.7%; D = 37.1%). Any long-acting bronchodilator (LABD) use and any dyspnea were significant predictors of GOLD A to D groups. The predicted MDS-GOLD group (A = 6.9%; B = 52.6%; C = 4.6%; D = 36.0%) showed good model fit (correctly predicted = 60.6%). Nursing home residents may underuse group-recommended LABD treatment (no LABD: B = 53.2%; C = 80.0%; D = 40.0%). CONCLUSION AND RELEVANCE: The MDS, completed routinely for US NH residents, could potentially be used to estimate COPD severity. Predicted COPD severity with additional validation could provide a map to evidence-based treatment guidelines and may help to individualize treatment pathways for NH residents.

The incidence and economic burden of extrapyramidal symptoms in patients with schizophrenia treated with second generation antipsychotics in a Medicaid population.

BACKGROUND: Extrapyramidal symptoms (EPS) are common side-effects of second-generation antipsychotics (SGA), that can negatively impact patient quality-of-life, and are associated with increased morbidity and mortality. This study examined the incidence and burden of EPS in patients with schizophrenia initiating SGAs. METHODS: Patients with schizophrenia initiating SGAs were identified in the MarketScan Multi-state Medicaid database from 1 January 2012 to 31 December 2018. Incidence of EPS (identified via ICD-9/ICD-10 diagnoses and medications) was assessed during the 12-months following SGA initiation. Cohorts with and without EPS were defined. Multivariate models were used to examine all-cause and schizophrenia-related hospitalizations and total costs in the 12 months following the first EPS claim (EPS) or randomly assigned index date (Non-EPS) while controlling for multiple baseline covariates. Logistic regression was used for hospitalization and two-part models were used for skewed cost data. RESULTS: A total of 11,642 patients with schizophrenia filled a prescription for an SGA; of which, 2,468 (21.2%) experienced EPS in the first year. The age- and gender-matched EPS group and non-EPS group included 2,295 and 5,607 patients, respectively. Multivariate analyses confirmed that EPS patients had 25% higher odds of all-cause (OR = 1.25; 95% CI = 1.11-1.40) and 75% increased odds of schizophrenia-related (OR = 1.75; 95% CI = 1.53-2.00) inpatient admissions compared to non-EPS patients. Multivariate adjustment of post-period costs between groups also found significant differences in both all-cause (EPS: $27,408 vs. non-EPS: $22,489, p < 0.001) and schizophrenia-related (EPS:$12,833 vs. non-EPS:$8,077, p < 0.0001) costs between the EPS and non-EPS cohorts. CONCLUSIONS: Over one-fifth of patients initiating treatment with atypical antipsychotics in this study developed EPS in the 12 months following SGA initiation. Extrapyramidal side-effects associated with atypical antipsychotics increase the risk of hospitalization and contribute to higher healthcare costs. For patients with schizophrenia, treatment options that minimize the risk of EPS may reduce the economic burden associated with the disease.

Point-in-time survey of healthcare resource utilization, employment, quality of life and caregiver status by disease severity in patients with schizophrenia in the US.

OBJECTIVE: The objective of this survey was to assess patient outcomes and caregiver status by disease severity among patients with schizophrenia in the United States. METHODS: A point-in-time survey was conducted between July and October 2019 via the Adelphi Schizophrenia Disease Specific Programme. Psychiatrists reported on their next 10 eligible patients with schizophrenia including demographics, disease severity, treatment history and hospitalizations. Patients receiving treatment for schizophrenia were classified as mild, moderate or severe based on disease severity. Regression models adjusted for age, sex and race/ethnicity. RESULTS: Psychiatrists (n = 124) reported on 435 mild, 401 moderate and 247 severe patients. Greater severity of schizophrenia was associated with a greater number of hospitalizations related to schizophrenia relapse in the previous 12 months (moderate vs. mild: adjusted incidence rate ratio (aIRR) [95% CI] = 2.17 [1.60-2.94]; severe vs. mild: aIRR = 5.45 [3.59-8.27]), lower full-time employment (moderate vs. mild: adjusted odds ratio (aOR) = 0.15 [0.08-0.28]; severe vs. mild: aOR = 0.02 [0.002-0.12]) and greater unemployment due to disability (moderate vs. mild: aOR = 4.24 [3.02-5.97]; severe vs. mild: aOR = 10.85 [6.85-17.17]). Patients with severe vs. mild schizophrenia had lower average quality of life (QoL) measured by the EuroQoL 5-dimension Health Index (difference = -0.16 [-0.23-0.09]). Among patients requiring care, patients with severe vs. mild schizophrenia received more caregiver hours per week (aIRR = 1.89 [1.25-2.84]). CONCLUSIONS: Greater severity of schizophrenia was associated with a significantly greater number of hospitalizations and greater unemployment due to disability. Compared with mild schizophrenia, severe schizophrenia was associated with worse patient QoL and greater caregiver hours.

Hospitalization risk in pediatric patients with bipolar disorder treated with lurasidone vs. other oral atypical antipsychotics: a real-world retrospective claims database study.

BACKGROUND: Real-world evidence on atypical antipsychotic (AAP) use in pediatric bipolar disorder is limited. OBJECTIVE: To assess the risk of all-cause and psychiatric hospitalization among pediatric patients with bipolar disorder when treated with lurasidone versus other atypical antipsychotics (AAPs). METHODS: This retrospective cohort study used commercial claims data (January 1, 2011 to June 30, 2017) to identify pediatric patients (age ≤17 years) with bipolar disorder treated with oral atypical antipsychotics (N = 16,201). The date of the first claim for an AAP defined the index date, with pre- and post-index periods of 180 days. Each month of the post-index period was categorized as monotherapy treatment with lurasidone, aripiprazole, olanzapine, quetiapine, or risperidone, no/minimal treatment, or other. The risk of all-cause and psychiatric hospitalizations (defined by a psychiatric diagnosis on the facility claim) was analyzed based on treatment in the current month, time-varying covariates (prior treatment-month classification, hospitalization in the prior month, emergency room visit in the prior month), and fixed covariates (age, gender, pervasive development disorder/mental retardation, disruptive behavior/conduct disorder, attention deficit hyperactivity disorder, depression, anxiety, adjustment disorder, obesity, diabetes, antidepressants, anxiolytics, other co-medication) using a marginal structural model. RESULTS: Treatment with aripiprazole (OR = 1.60, 95% CI: 1.08-2.36) and olanzapine (OR = 1.68, CI: 1.03-2.71) was associated with significantly higher odds of all-cause hospitalizations compared to lurasidone, but treatment with quetiapine (OR = 1.03, CI: 0.69-1.54) or risperidone (OR = 1.02, CI: 0.68-1.53) was not. Similarly, treatment with aripiprazole (OR = 1.61, 95% CI: 1.08-2.38) and olanzapine (OR = 1.73, CI: 1.06-2.80) was associated with significantly higher odds of psychiatric hospitalizations compared to lurasidone, but treatment with quetiapine (OR = 1.02, CI: 0.68-1.54) or risperidone (OR = 1.01, CI: 0.67-1.51) was not. CONCLUSION: In usual clinical care, pediatric patients with bipolar disorder treated with lurasidone had a significantly lower risk of all-cause and psychiatric hospitalizations when compared to aripiprazole and olanzapine, but not quetiapine or risperidone.

Comparative economic outcomes in patients with focal seizures initiating eslicarbazepine acetate versus brivaracetam as their first adjunctive ASD.

AIMS: To study the association between initiation of first adjunctive therapy with eslicarbazepine acetate (ESL) vs. brivaracetam (BRV) on healthcare resource utilization (HCRU) and charges among patients with treated focal seizures (FS). MATERIALS AND METHODS: Symphony Health's Integrated Dataverse (IDV) claims data (1 April 2015 to 30 June 2018) were used to identify two cohorts as first adjunctive therapy with ESL or BRV following a generic anti-seizure drug (ASD). The index date was the earliest claim for a new ESL or BRV prescription. Key inclusion criteria were only 1 generic ASD in the 12 months before the index date; ≥1 medical claim with an FS diagnosis. Unit of analysis was the 90-day person-time-block. Changes in HCRU and charges were assessed using a difference-in-differences framework. Both unadjusted and adjusted analyses were performed. The adjusted model utilized person-specific fixed effects and propensity score-based weighting to control for differences in baseline covariates. Bias-corrected bootstrap confidence intervals (CIs) were calculated for charge outcomes. RESULTS: 208 and 137 patients initiated first adjunctive therapy with ESL (43.7 years, 51.9% female) or BRV (39.3 years, 51.8% female). Patients in the ESL cohort had numerically larger reductions in all-cause and FS-related inpatient hospitalizations and outpatient visits and FS-related emergency department visits. Compared to patients initiating BRV, patients treated with ESL had significantly larger reductions in total charges (-$3,446, CI: -$13,716, -$425), all-cause (-$3,166, CI: -$13,991, -$323) and FS-related (-$2,969, CI: -$21,547, -$842) medical charges, all-cause (-$3,397, CI: -$15,676, -$818) and FS-related (-$2,863, CI: -$19,707, -$787) outpatient charges, and non-ASD-related prescription charges (-$420, CI: -$1,058, -$78). LIMITATIONS: Claims may be missing, or miscoded; outcomes may be influenced by variables not accounted for in the analysis; only information on submitted charges was included. CONCLUSIONS: Among patients with FS, initiation of first adjunctive therapy with ESL was associated with significantly larger reductions in medical and non-ASD-related prescriptions charges compared to BRV.

Hospitalization Risk for Adults with Bipolar I Disorder Treated with Oral Atypical Antipsychotics as Adjunctive Therapy with Mood Stabilizers: A Retrospective Analysis of Medicaid Claims Data.

Background: Atypical antipsychotics (AAPs) with mood stabilizers are recommended as a first-line treatment for patients with bipolar disorder. No studies have compared the inpatient health care resource utilization for patients with bipolar disorder treated with lurasidone as adjunctive therapy with mood stabilizers compared with other oral AAPs. Objective: To compare the risk of hospitalization for adult Medicaid beneficiaries with bipolar I disorder when treated with lurasidone compared with other oral AAPs as adjunctive therapy with mood stabilizers. Methods: This retrospective cohort study used the MarketScan Research Databases Multi-State Medicaid Database (IBM, Armonk, NY) claims data to assess patients with bipolar I disorder between January 1, 2014, and June 30, 2019. Adult patients who initiated oral AAP treatment with mood stabilizers (index date) and who were continuously enrolled 12 months before (pre-index) and 24 months after (post-index) the index date were included. Treatment categories assigned by patient-month included lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone with mood stabilizers; no/minimal treatment; AAP monotherapy; and other. Marginal structural models were performed to estimate the all-cause and psychiatric hospitalization rates and hospital length of stay associated with each adjunctive AAP therapy by controlling for both time-invariant and time-varying confounders. Results: Adults with bipolar I disorder (N = 11,426; mean age = 39.4 years; female=73%) treated with an adjunctive oral AAP with mood stabilizers during the index month were categorized into lurasidone (12%), aripiprazole (17%), olanzapine (7%), quetiapine (32%), risperidone (11%), ziprasidone (7%), or other (15%) treatment groups. The adjusted odds of all-cause and psychiatric hospitalization were significantly higher for olanzapine (all causes: adjusted odds ratio [aOR] = 1.59; 95% CI, 1.13-2.25; psychiatric: aOR = 1.61, 95% CI, 1.12-2.32), quetiapine (all-causes: aOR = 1.27, 95% CI, 1.01-1.58; psychiatric: aOR = 1.28, 95% CI, 1.02-1.59), and ziprasidone (all-causes: aOR = 1.68, 95% CI, 1.05-2.66; psychiatric: aOR = 1.55, 95% CI, 1.02-2.35) compared with lurasidone with mood stabilizers. The adjusted odds of all-cause and psychiatric hospitalizations were numerically lower for lurasidone compared with aripiprazole. The all-cause hospital length of stay per 100 patient-months was significantly higher for olanzapine (20.3 days) and quetiapine (16.0 days) compared with lurasidone (12.2 days, both P values < 0.05). Conclusions: In a Medicaid population, adults with bipolar I disorder treated with lurasidone as adjunctive therapy with mood stabilizers had significantly lower all-cause and psychiatric hospitalization rates compared with olanzapine, quetiapine, and ziprasidone. Fewer hospitalizations may reduce the economic burden associated with bipolar disorder. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).

Healthcare Resource Utilization Among Patients with Focal Seizures Treated with Eslicarbazepine Acetate in the US Long-Term Care Setting: A Retrospective Claims Database Analysis.

INTRODUCTION: The aim of this study was to compare healthcare resource utilization (HCRU) before and after initiation of eslicarbazepine acetate (ESL) in the long-term care (LTC) setting (rehabilitation center, mental health center, LTC non-skilled nursing facility/assisted-living facility, home health, assisted living, nursing home, other/unknown). METHODS: This retrospective analysis used IQVIA's New Data Warehouse, which includes deterministically linked LTC, prescription, and professional fee claims data and IQVIA Hospital Charge Data Master database. The study period was 1 April 2013 to 31 December 2019. The index date was the date of ESL initiation in the LTC setting. Inclusion criteria were: (1) ≥ 1 new ESL prescription between 1 April 2014 and 31 December 2018; (2) diagnosis of focal seizure (FS) during the 12 months pre-index date; and (3) no ESL prescription during the 12-month period pre-index. A 12-month pre-post analysis compared epilepsy-specific and all-cause HCRU before and after ESL initiation. Categorical variables were compared with McNemar's tests. RESULTS: A total of 307 patients (mean age 52.2 years, 57.7% male) with FS were included, of whom 24.8% were in nursing homes. Patients used a mean of 3.1 antiseizure drugs prior to initiation of ESL, and 87.9% of patients initiated ESL as adjunctive treatment. There were significant reductions in proportion of patients with epilepsy specific physician office visits, emergency department (ED) visits, hospitalizations, and all-cause physician office visits and hospitalizations in the post-index period compared to the pre-index period (P < 0.05). Similar results were observed in sensitivity (patients with an epilepsy diagnosis) and subgroup analyses [presence or absence of intellectual developmental disorders or age (≥ 65 and < 65 years)]. CONCLUSION: Proportion of patients with epilepsy-specific physician office visits, ED visits, hospitalizations, and all-cause physician office visits and hospitalizations were significantly reduced following initiation of ESL in patients with FS in LTC.

Comparative Economic Outcomes in Patients with Focal Seizure Initiating First-Line Eslicarbazepine Acetate Monotherapy versus Generic Antiseizure Drugs.

OBJECTIVE: To examine the association between initiating first-line (1L) monotherapy with eslicarbazepine acetate (ESL) vs a generic antiseizure drug (ASD) and healthcare resource utilization (HCRU) and charges in adults with treated focal seizures (FS). METHODS: This was a retrospective analysis of Symphony Health's Integrated Dataverse® open-source claims data. Two cohorts were identified as having initiated 1L monotherapy with ESL or literature-defined generic ASDs. Linear regression models with person fixed effects and inverse probability treatment weights assessed the relative additional changes in HCRU and charges among patients who received ESL compared to generic ASD. RESULTS: A total of 250 and 43,220 patients initiated ESL (48.3 years; 57.2% female) or a generic ASD (54.5 years; 58.1% female), respectively. Compared to patients initiating a generic ASD, patients treated with ESL had additional reductions of 11.8 percentage points in the likelihood of any all-cause outpatient visits (P<0.001), 7.4 percentage points in the likelihood of any emergency department (ED) visits (P=0.013), and 22.7 percentage points in the likelihood of any FS-related outpatient visits (P<0.001). Patients initiating ESL had greater reductions in mean charges for all-cause medical ($2620; P=0.002), outpatient ($1995; P=0.005), and non-FS-related medical ($2708; P<0.001) services. Patients initiating ESL had greater relative increases in mean total prescription ($1368; P<0.001) and ASD-related prescription ($1636; P<0.001) charges, but greater relative reductions in non-ASD prescription ($269; P=0.032) charges. The increases in prescription charges were of a lower magnitude than the decreases in medical charges. CONCLUSION: Initiation of ESL as 1L monotherapy was associated with statistically significantly greater reductions in any use of several all-cause and FS-related services, number of visits, and charges compared to initiation of a generic ASD as 1L monotherapy in patients with FS. Initiation of a generic ASD as 1L monotherapy was associated with significantly smaller increases in total prescription charges and ASD-related prescription charges.

Hospitalization risk among adults with bipolar I disorder treated with lurasidone versus other oral atypical antipsychotics: a retrospective analysis of Medicaid claims data.

OBJECTIVE: To compare the risk of hospitalization for adult Medicaid beneficiaries with bipolar I disorder treated with lurasidone vs. other oral atypical antipsychotics (AAPs) as monotherapy. METHODS: A retrospective cohort study of the IBM MarketScan Multi-State Medicaid Claims database identified adults with bipolar I disorder who initiated an AAP (index date) between 1 January 2014 and 30 June 2019. Patients were continuously enrolled 12 months pre- and 24 months post-index date. Each month during the post-index period was categorized as monotherapy with lurasidone, aripiprazole, olanzapine, quetiapine or risperidone, no/minimal treatment, or other. Marginal structural models were performed to estimate hospitalization risk and length of stay (LOS) (all-cause and bipolar I disorder-related) compared to lurasidone. RESULTS: The analysis included 8262 adults. Compared to lurasidone, the adjusted odds ratios (aORs) of all-cause hospitalization were significantly higher for olanzapine (aOR = 1.60, 95% CI = 1.09-2.10) and quetiapine (aOR = 1.54, 95% CI = 1.18-1.89). The risk was significantly higher for bipolar I disorder-related hospitalization for quetiapine (aOR = 1.57, 95% CI = 1.10-2.04) and risperidone (aOR = 1.80, 95% CI = 1.04-2.56) compared to lurasidone. The bipolar I disorder-related LOS per 100 patient-months was more than twice as long for quetiapine (8.42 days) compared to lurasidone (3.97 days, p < .01). CONCLUSIONS: Lurasidone-treated adult Medicaid patients with bipolar I disorder had significantly lower risk of all-cause hospitalization than those treated with olanzapine and quetiapine and lower risk of bipolar I disorder-related hospitalization than quetiapine and risperidone. Bipolar I disorder-related hospital LOS was significantly shorter for patients treated with lurasidone compared to quetiapine.

Healthcare resource utilization, costs and treatment patterns in patients with bipolar disorder treated with lurasidone or cariprazine.

OBJECTIVE: To compare healthcare resource utilization (HCRU), costs, and treatment adherence and persistence for patients with bipolar disorder treated with lurasidone or cariprazine. METHODS: Adult patients with bipolar disorder who initiated lurasidone or cariprazine as monotherapy or adjunctive therapy between 1 January 2016 and 30 June 2019 were identified from the IBM MarketScan Commercial and Medicare Supplemental Database. The date of the first claim for lurasidone or cariprazine was defined as the index date. A difference-in-difference (DID) analysis, which mitigated bias by using each cohort as its own control, compared the changes in HCRU and costs from 6-months pre-treatment (baseline) to 6-months post-treatment (follow-up) between the two cohorts. Treatment adherence (medication possession ratio and proportion of days covered) and persistence (time to discontinuation) were assessed during the 6-month post-treatment period. Adjusted analyses were conducted using inverse probability of treatment weighting on HCRU, costs, and time to discontinuation. RESULTS: A total of 16,683 patients treated with lurasidone and 4,128 patients treated with cariprazine were identified. Average age (39-40) and proportion female (68-71%) were similar between cohorts. Both cohorts had reductions in hospitalizations from baseline to follow-up, and the decrease was significantly greater for the lurasidone cohort compared to the cariprazine cohort (change in the proportions of patients with all-cause hospitalizations: -5.3% vs. -2.5%, DID = -2.8%, p<.001). The total healthcare costs increased from baseline to follow-up in both cohorts, and the increase was significantly lower for the lurasidone cohort (change in total all-cause healthcare cost per person: $3,413 vs. $4,642, DID=-$1,228, p = .022). The lurasidone cohort had significantly lower risk of discontinuing treatment (hazard ratio = 0.86, p<.001) than the cariprazine cohort. CONCLUSIONS: Patients with bipolar disorder treated with lurasidone had greater reductions in hospitalizations from 6-months pre-treatment to 6-months post-treatment and had a lower increase in total costs compared to patients treated with cariprazine.

Cost-Effectiveness of Apomorphine Sublingual Film as an "On-Demand" Treatment for "OFF" Episodes in Patients with Parkinson's Disease.

Background: "On-demand" treatments approved in the United States (US) for "OFF" episodes in Parkinson's disease (PD) include apomorphine hydrochloride injection (SC-APO), apomorphine sublingual film (APL), and levodopa inhalation powder (CVT-301). APL received US approval in 2020, and its cost-effectiveness has not been compared with SC-APO and CVT-301. Objective: To develop a cost-effectiveness analysis model comparing APL versus SC-APO and CVT-301 for treatment of patients with PD experiencing "OFF" episodes from a US payer perspective. Methods: The model estimated total costs and effectiveness for each comparator arm, informed from the treatments' pivotal studies or literature, over a 10-year horizon. Total and incremental patient costs (in 2020 US dollars), total time spent without "OFF" episode symptoms, and quality-adjusted life years (QALY) gained were summarized and compared. Incremental cost-effectiveness ratios for APL versus SC-APO and CVT-301 were estimated and expressed as incremental patient costs per patient QALY gained and incremental cost per "OFF" hour avoided. Scenario analyses varying inputs and including caregiver costs were also conducted. Results: In the base case, APL had the lowest total "on-demand" treatment costs ($42,095) compared with SC-APO ($276,320; difference: -$234,225) and CVT-301 ($69,577; difference: -$27,482) over the 10-year horizon. APL was also associated with the highest utility, with incremental QALYs of 0.019 versus SC-APO and 0.235 versus CVT-301. APL was dominant over CVT-301 in terms of incremental cost per "OFF" hour, and dominant over both CVT-301 and SC-APO in terms of incremental cost per QALY gained. In all scenario analyses, APL was dominant against both SC-APO and CVT-301, confirming the robustness of the base-case results. Discussion: APL was dominant compared with both comparator arms, being less costly and more effective on average than SC-APO and CVT-301 in terms of QALYs. For SC-APO, cost-effectiveness of APL was driven by lower "on-demand" treatment costs and adverse event-related disutilities. For CVT-301, cost-effectiveness of APL was driven by lower "on-demand" treatment costs and substantially higher efficacy. Conclusions: From a US payer perspective, APL represents a cost-effective option compared with SC-APO and CVT-301 for treatment of "OFF" episodes in patients with PD.

Impact of Early Initiation of Eslicarbazepine Acetate on Economic Outcomes Among Patients with Focal Seizure: Results from Retrospective Database Analyses.

INTRODUCTION: This study assessed the association between early initiation of eslicarbazepine acetate (ESL) as first-line therapy (1L cohort) or as first adjunctive regimen to either levetiracetam (LEV) or lamotrigine (LTG) (add-on cohort), and healthcare resource utilization (HCRU) and charges among adults with treated focal seizures (FS). METHODS: This retrospective, longitudinal cohort analysis used Symphony Health's Integrated Dataverse (IDV®) claims data to identify patients aged ≥ 18 years with a diagnosis of FS who had a new prescription for ESL between April 2015 and June 2018. Baseline was the 90-day period immediately prior to the date of the first-dispensed claim for ESL (index date) with a follow-up of 1-4 consecutive 90-day periods. Linear regression models were estimated to assess changes in HCRU and charge outcomes. RESULTS: There were 274 and 153 patients who received ESL in the 1L cohort and add-on cohort, respectively. The 1L cohort experienced significant reductions from baseline during follow-up in all-cause inpatient (IP; P < 0.0001), emergency room (ER; P < 0.0001), and outpatient (OP; P < 0.0001) visits; FS-related IP (P = 0.006) and OP (P < 0.0001) visits; total, medical, all-cause ER and OP, and FS-related medical charges (P < 0.05); and significant increases in total prescription and anti-seizure drug (ASD)-related prescription (P < 0.001) charges. The add-on cohort experienced significant reductions in all-cause IP (P = 0.009) and all-cause and FS-related OP visits (P < 0.0001 for both) and significant increases in total prescription and ASD-related prescription (P < 0.001) charges during the follow-up period. In both cohorts, the increases in prescription charges were smaller than the reduction in total medical charges. CONCLUSION: Early initiation of ESL as 1L or add-on therapy was associated with statistically significant reductions in all-cause IP and all-cause and FS-related OP visits during follow-up compared to baseline. The 1L cohort also had statistically significant reductions in all-cause ER visits, FS-related IP visits, and total, medical, all-cause ER and OP, and FS-related medical charges. Knowledge of healthcare resource utilization (HCRU) and costs of care in patients taking anti-seizure drugs (ASDs) is required to inform prescribing and formulary decision-making. Levetiracetam (LEV) and lamotrigine (LTG) are the most widely used first-line (1L) ASDs in the USA. Eslicarbazepine acetate (ESL), a third-generation ASD with sodium channel-modulating activity, is typically used in later lines of therapy. Sodium channel-blocking anti-seizure drugs may represent an effective treatment option for patients with epilepsy in the 1L setting. This study assessed the association between early initiation of ESL as 1L therapy (1L cohort) or as first adjunctive therapy to either LEV or LTG (add-on cohort), and HCRU and charges among adults with treated focal seizures (FS). The results showed that following ESL initiation the 1L cohort experienced significant reductions in all-cause inpatient (IP), emergency room (ER), and outpatient (OP) visits; FS-related IP and OP visits; and total, medical, all-cause ER and OP, and FS-related medical charges, and significant increases in total prescription and ASD-related prescription charges. The add-on cohort showed significant reductions in all-cause IP and all-cause and FS-related OP visits and significant increases in total prescription and ASD-related prescription charges. In both cohorts, the increases in prescription charges were smaller than the reduction in total medical charges. These data imply that use of ESL as 1L therapy in adult patients with FS could help conserve scarce healthcare resources and reduce the burden on healthcare budgets. These findings may inform selection of ASD therapy in this patient population.

Associations between seizure severity change and patient characteristics, changes in seizure frequency, and health-related quality of life in patients with focal seizures treated with adjunctive eslicarbazepine acetate: Post hoc analyses of clinical trial results.

The relationships between seizure severity change and patient characteristics, changes in seizure frequency, and health-related quality of life (HRQoL) may be important for determining the overall impact of medication therapy on patients with epilepsy. The objectives of these post hoc analyses of the global Phase III 093-0304 trial (NCT00988429, Study 304) of adjunctive eslicarbazepine acetate (ESL) in patients with refractory focal (partial-onset) seizures (FS) were to evaluate associations between seizure severity change, measured by the Seizure Severity Questionnaire (SSQ), and 1) patient characteristics, 2) seizure frequency change, standardized as the seizure frequency (SSF) per 28-day period, and 3) change in HRQoL, evaluated by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31) and the Montgomery-Åsberg Depression Rating Scale (MADRS). The analyses were conducted on the per-protocol population (PPP) of patients who were randomized to a placebo arm (n = 188) or an ESL-active group that included treatment with adjunctive ESL 800 mg once daily (QD; n = 184) or adjunctive ESL 1200 mg QD (n = 175). General linear models (GLM) were used to measure the association between SSQ change and patient baseline characteristics or percentage change in the SSF from baseline. Associations between changes in the SSQ and changes in the QOLIE-31 and MADRS were examined using GLM with patient baseline characteristics as covariates. Subgroup analyses were performed for patients in the ESL-active group and those treated with ESL 800 mg or ESL 1200 mg. Minimal clinically important difference (MCIDs) thresholds were used to assess improvements in SSQ scores. The analyses included 547 per-protocol patients. Patients using 1 antiepileptic drug (AED) at baseline had greater improvements in the SSQ compared with those receiving 2 AEDs (P = 0.0606). Treatment with ESL 1200 mg was significantly associated with clinically meaningful improvements in the SSQ (P = 0.0005). The SSQ improvements were significantly associated with an SSF reduction of ≥75%, compared with no reduction (P < 0.0001). In the PPP and the ESL-active group, SSQ improvements were significantly associated with improvements in QOLIE-31 Total Score (TS; P < 0.0001) and the Seizure Worry (SW; P < 0.0001) and Social Functioning (SF; P = 0.0030) subscales. In the ESL 1200 mg subgroup, SSQ improvements were significantly associated with improvements in QOLIE-31 TS (P < 0.0001) and the SW (P < 0.0001) and Energy/Fatigue (EF; P = 0.0007) subscales. In the ESL 800 mg subgroup, improvements in the SSQ were significantly associated with improvements in QOLIE-31 TS (P = 0.0362) and the SW (P = 0.0241) subscale. There was no significant association between changes in the SSQ and changes in the MADRS in patients treated with ESL. These findings demonstrated that in this clinical trial population, adding ESL to baseline AED therapy had utility for decreasing seizure severity and improving HRQoL. There were no significant associations between changes in seizure severity and changes in depressive symptoms in patients with FS.

Healthcare Resource Utilization Pre- and Post-Initiation of Eslicarbazepine Acetate Among Pediatric Patients with Focal Seizure: Evidence from Routine Clinical Practice.

OBJECTIVE: To examine the impact of initiating treatment with eslicarbazepine acetate (ESL) on healthcare resource utilization (HCRU) among pediatric patients with focal seizures (FS). METHODS: This retrospective study used Symphony Health's Integrated Dataverse® claims data. Patients aged 4 to 17 years with a diagnosis of FS and a new prescription for ESL between April 2015 and June 2018 were included and defined as the overall patient population. Index date was the first dispensed claim for ESL. Baseline period was the 90-day block immediately prior to the index date. The follow-up period comprised up to 4 consecutive 90-day blocks immediately following the index date. Subgroups were defined based on the presence (DP+) or absence (DP-) of developmental and/or psychiatric disorders at baseline. All-cause and FS-related inpatient (IP), emergency room (ER), outpatient (OP) hospital, and office (OF) visits were measured during the follow-up period. Reduction in HCRU per block in the post-ESL period was assessed using fixed-effects linear regression models. RESULTS: A total of 234 patients were included in the overall study population, of whom 86 (36.8%) were DP+ and 148 (63.2%) were DP-. Relative to the baseline period, significant reductions were observed in the overall population for all-cause ER (P=0.001), OP (P<0.001), and OF (P<0.001) visits and FS-related IP (P=0.037) and OF (P<0.001) visits in the follow-up period. Among DP+ and DP- patients, significant reductions were observed for all-cause ER (DP+: P=0.024; DP-: P=0.017), OP (DP+: P<0.001; DP-: P=0.035), and OF (DP+: P=0.004; DP-: P=0.001) visits during the follow-up period. No significant differences were observed between DP+ and DP- patients in the change in all-cause or FS-related HCRU from baseline to the follow-up period. CONCLUSION: Pediatric patients with FS (DP+ and DP-) who initiated ESL had significant reductions in all-cause ER, OP, and OF visits and FS-related IP and OF visits.