The economic and humanistic burden of bipolar disorder in adults in the United States.

BACKGROUND: Bipolar disorder is associated with functional impairment and diminished health-related quality of life (HRQoL). The purpose of this study was to estimate the annual per patient direct healthcare costs, indirect costs, and HRQoL of patients with bipolar disorder by depressive symptom severity and overall compared to the general population in the US. METHODS: This cross-sectional study used self-reported data from the 2020 US National Health and Wellness Survey. Adult respondents who reported bipolar disorder symptoms in the past 12 months and/or a diagnosis of bipolar disorder were identified (bipolar disorder cohort) and were further classified by depressive symptom severity based on Patient Health Questionnaire (PHQ-9) scores (none/mild = 0-9, moderate = 10-14, severe = 15-27). Annualized direct healthcare costs and indirect costs were calculated from 6-month healthcare resource utilization and work productivity, respectively. A general population cohort was constructed using 2:1 propensity score matching. Multivariate regression models of all-cause hospitalizations in the past 6 months, annualized direct healthcare costs, annualized indirect costs, and HRQoL (eg, EuroQol 5-Dimension Health Questionnaire (EQ-5D)) controlled for confounders (demographic and clinical characteristics). RESULTS: Of 3583 adults meeting pre-specified criteria for bipolar disorder, 1401 (39.1%) reported none/mild, 889 (24.8%) moderate, and 1293 (36.1%) severe depressive symptom severity. Additionally, 3285 (91.7%) were matched to 6570 adults in the general population. Compared to the general population, adjusted mean hospitalizations (0.53 vs. 0.30), annualized per patient direct healthcare costs ($20,846 vs. $11,391), and indirect costs ($14,795 vs. $9274) were significantly greater for the bipolar disorder cohort (all p < 0.001); adjusted HRQoL (EQ-5D: 0.69 vs. 0.79) was significantly worse (p < 0.001). By depressive symptom severity, adjusted mean hospitalizations (none/mild = 0.30, moderate = 0.50, severe = 0.46), direct healthcare costs ($14,389, $22,302, $21,341), and indirect costs ($10,799, $17,109, $18,470) were significantly greater for moderate and severe compared to none/mild depressive symptom severity (all p < 0.01); adjusted HRQoL (EQ-5D: 0.77, 0.67, 0.59) was significantly worse (p < 0.001). CONCLUSIONS: Among respondents with bipolar disorder, those with moderate to severe depression had greater direct healthcare costs and indirect costs as well as worse HRQoL than those with mild or no depressive symptoms. Treatment targeting reduction in depressive symptoms may reduce the economic and humanistic burden of bipolar disorder.

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.

The impact of lurasidone on functioning and indirect costs in adults with bipolar depression: a post-hoc analysis.

OBJECTIVE: The aim of this post-hoc analysis was to assess the impact of lurasidone monotherapy on functional impairment, productivity, and associated indirect costs in patients with bipolar depression. METHODS: Data were analyzed from a 6-week randomized, double-blind (DB; NCT00868699), placebo-controlled trial of lurasidone monotherapy and a 6-month open label extension (OLE; NCT00868959) study. Patients with bipolar depression who completed the 6-week DB trial were subsequently enrolled in the OLE. Analysis of the OLE was limited to patients who either continued lurasidone (LUR-LUR) or switched from placebo to lurasidone monotherapy (PBO-LUR). The Sheehan Disability Scale (SDS), which measures functional impairment and productivity, was collected at DB baseline, DB week 6/OLE baseline, OLE month 3, and OLE month 6. Annual indirect costs were calculated based on days lost or unproductive from work/school due to symptoms. Effect sizes (ES) in functioning and days lost/unproductive were reported for the DB trial and mean changes for the OLE. RESULTS: A total of 485 patients were enrolled in the DB trial (lurasidone: n = 323; placebo: n = 162) and 316 were in the lurasidone monotherapy group during the OLE (LUR-LUR: n = 210; PBO-LUR: n = 106). In the DB trial, improvements in functioning (work: ES = 0.36, p = .0071; social: ES = 0.55, p < .0001; family: ES = 0.50, p < .0001) were significantly greater for lurasidone compared to placebo. Reductions in days lost (ES = 0.33, p = .0050) and unproductive (ES = 0.45, p = .0001) were significantly higher for lurasidone vs. placebo. This resulted in a greater reduction in indirect costs for lurasidone vs. placebo (least squares mean (standard error) = -$32,322 ($2,100) vs. -$20,091 ($2,838)). Improvements in functioning and productivity were sustained during the 6-month OLE for both LUR-LUR and PBO-LUR. CONCLUSIONS: Lurasidone monotherapy for the treatment of bipolar depression significantly improved functioning and reduced indirect costs vs. placebo at week 6. Significant improvements in functioning and productivity were sustained for 6 months for both LUR-LUR and PBO-LUR.

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 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.

Reduction in Hospital Readmission Rates Among Medicare Beneficiaries With Chronic Obstructive Pulmonary Disease: A Real-world Outcomes Study of Nebulized Bronchodilators.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a common condition responsible for substantial morbidity, mortality, and costs in the United States. The economic burden of COPD is driven primarily by hospitalizations, with 1 in 5 hospitalized patients experiencing a 30-day readmission. Bronchodilators, delivered via handheld inhalers or nebulizers, are the mainstay of therapy for COPD. However, differences in outcomes between short- and long-acting therapies are unclear. We examined real-world differences in 30-day readmission and exacerbation rates between Medicare beneficiaries with COPD treated with a nebulized long-acting beta2-agonist (arformoterol tartrate [ARF]) and beneficiaries treated with a nebulized short-acting beta2-agonist (SABA) for maintenance therapy after hospital discharge. METHODS: Truven MarketScan Hospital Drug Database and Medicare files were probabilistically matched between 2009 and 2013 to identify beneficiaries who were aged ≥65 years and discharged from a hospital with a primary COPD diagnosis or a secondary COPD diagnosis and a primary diagnosis for another respiratory condition. Matching was performed by using COPD hospitalization date (±7 days) and source, length of stay (±1 day), discharge date and destination, and hospital region. After applying additional inclusion/exclusion criteria, 2 cohorts were created: nebulized ARF users (n = 953) and nebulized SABA users (n = 6939). Logistic regression analyses were used to examine 30-day readmission (all-cause and COPD related) and exacerbation rates. Odds ratios (ORs), 95% CIs, and P values were computed. FINDINGS: On average, nebulized SABA users had more comorbidities than nebulized ARF users, including diabetes, atrial fibrillation, renal disease, musculoskeletal disease, myocardial infarction, and cognitive impairment (all, P < 0.0001). However, nebulized ARF users had a higher average COPD severity score than nebulized SABA users (49.5 v. 38.0; P < 0.001). COPD therapies at baseline were similar in both cohorts and included systemic corticosteroids (≥65%), short-acting bronchodilators (≥33%), and inhaled corticosteroids + long-acting beta2-agonists (30%). After adjusting for sociodemographic and hospital characteristics, concomitant medications, and case-mix, nebulized ARF users had 27% lower odds of an all-cause readmission (OR, 0.73; 95% CI, 0.59-0.92; P = 0.008) and 23% lower odds of a COPD-related readmission (OR, 0.77; 95% CI, 0.60-0.98; P = 0.032) at 30 days compared with users of a nebulized SABA. No difference was found in 30-day exacerbation rates between the cohorts. IMPLICATIONS: Nebulized ARF users had lower 30-day readmission rates, greater COPD severity, and fewer comorbidities than nebulized SABA users. In this population, maintenance treatment with ARF reduced costly COPD outcomes.

Exacerbations, Health Resource Utilization, and Costs Among Medicare Beneficiaries with Chronic Obstructive Pulmonary Disease Treated with Nebulized Arformoterol Following a Respiratory Event.

BACKGROUND: Long-acting beta2-agonists (LABAs), with or without inhaled corticosteroids (ICSs), delivered by handheld inhalers or nebulizers are recommended as maintenance therapy in chronic obstructive pulmonary disease (COPD). This study evaluated exacerbations, health resource utilization (HRU), and costs among Medicare beneficiaries with COPD on handheld ICS+LABA who switched to nebulized arformoterol (ARF) or continued ICS+LABA following a respiratory event. METHODS: Using Medicare claims, we identified beneficiaries with COPD (international classification of disease, 9th revision, clinical modification [ICD-9-CM] 490-492.xx, 494.xx, 496.xx) between 2010-2014 who had ≥ 1 year of continuous enrollment in Parts A, B, and D; ≥ 2 COPD-related outpatient visits ≥ 30 days apart or ≥ 1 hospitalization(s); ICS+LABA use 90-days before ARF initiation; and a respiratory event (COPD-related hospitalization or emergency department [ED] visit < 30 days before ARF initiation). Using propensity scores, 423 beneficiaries who switched to ARF were matched to 423 beneficiaries who continued on handheld ICS+LABA (controls). Difference-in-difference regression models examined outcomes at 180-days follow-up. RESULTS: Beneficiaries who switched to ARF had 1.5 fewer exacerbations (p=0.015) but no difference in hospitalizations and ED visits compared to controls. Durable medical equipment (DME) costs were higher among ARF users than controls ($1590), yet total health care costs were similar due to cost offsets by ARF in pharmacy (-$794), inpatient (-$524), and outpatient care (-$65). ARF accounted for 55% ($886.63) of DME costs, with the remaining costs attributed to oxygen therapy ($428.10) and nebulized corticosteroids ($590.85). CONCLUSIONS: Switching from handheld ICS+LABA to nebulized ARF resulted in fewer COPD exacerbations among Medicare beneficiaries. Nebulized LABAs may improve outcomes in selected patients with COPD.

Predictors of Nebulized Arformoterol Treatment: A Retrospective Analysis of Medicare Beneficiaries with Chronic Obstructive Pulmonary Disease.

This study examined sociodemographic and clinical characteristics, treatment patterns, and health resource utilization among Medicare beneficiaries with chronic obstructive pulmonary disease (COPD) to identify predictors of nebulized arformoterol treatment. Using Medicare administrative data from 2010 to 2014, beneficiaries with ≥2 COPD outpatient visits ≥30 d apart or ≥1 COPD-related hospitalization(s) (ICD-9-CM 491.xx, 492.xx, and 496) were identified. Inclusion criteria required ≥1 COPD medication claim(s) and continuous enrollment in Parts A, B, and D. Four cohorts were identified: (a) 11,887 arformoterol users, (b) a subsample of arformoterol users (n = 1,778) who were hospitalized and discharged 30 d before initiating arformoterol, (c) 450,178 controls who had not received arformoterol, and (d) a subsample of controls (n = 21,910) who had hospitalizations. Logistic regression analysis was used to evaluate predictors of arformoterol treatment. The majority of beneficiaries were older than 70 years of age, female, Caucasian, and 47% were dual-eligible. The strongest predictors of arformoterol treatment were oxygen therapy, systemic corticosteroid or methylxanthine use, an exacerbation, a COPD-related hospitalization, and receiving care from a pulmonologist (all p < .001). Dual-eligibility, being a racial/ethnic minority, and having severe psychiatric comorbidity or immunodeficiency lowered the odds of receiving nebulized arformoterol (all p < .001). Among beneficiaries with recent hospitalizations, exacerbations and COPD-related admissions increased the odds of receiving arformoterol (p < .001). Nebulized arformoterol treatment was more likely to be initiated in sicker patients with COPD. Ensuring access to nebulized maintenance therapy is important and particularly warranted for COPD populations with greater medical needs.

Medication management patterns among Medicare beneficiaries with chronic obstructive pulmonary disease who initiate nebulized arformoterol treatment.

Purpose: Global evidence-based treatment strategies for chronic obstructive pulmonary disease (COPD) recommend using long-acting bronchodilators (LABDs) as maintenance therapy. However, COPD patients are often undertreated. We examined COPD treatment patterns among Medicare beneficiaries who initiated arformoterol tartrate, a nebulized long-acting beta2 agonist (LABA), and identified the predictors of initiation. Methods: Using a 100% sample of Medicare administrative data, we identified beneficiaries with a COPD diagnosis (ICD-9 490-492.xx, 494.xx, 496.xx) between 2010 and 2014 who had ≥1 year of continuous enrollment in Parts A, B, and D, and ≥2 COPD-related outpatient visits within 30 days or ≥1 hospitalization(s). After applying inclusion/exclusion criteria, three cohorts were identified: (1) study group beneficiaries who received nebulized arformoterol (n=11,886), (2) a subset of the study group with no LABD use 90 days prior to initiating arformoterol (n=5,542), and (3) control group beneficiaries with no nebulized LABA use (n=220,429). Logistic regression was used to evaluate predictors of arformoterol initiation. Odds ratios (ORs), 95% confidence intervals (CIs), and p values were computed. Results: Among arformoterol users, 47% (n=5,542) had received no LABDs 90 days prior to initiating arformoterol. These beneficiaries were being treated with a nebulized (50%) or inhaled (37%) short-acting bronchodilator or a systemic corticosteroid (46%), and many received antibiotics (37%). Compared to controls, beneficiaries who initiated arformoterol were significantly more likely to have had an exacerbation, a COPD-related hospitalization, and a pulmonologist or respiratory therapist visit prior to initiation (all p<0.05). Beneficiaries with moderate/severe psychiatric comorbidity or dual-eligible status were significantly less likely to initiate arformoterol, as compared to controls (all p<0.05). Conclusion: Medicare beneficiaries who initiated nebulized arformoterol therapy had more exacerbations and hospitalizations than controls 90 days prior to initiation. Findings revealed inadequate use of maintenance medications, suggesting a lack of compliance with evidence-based treatment guidelines.

Cost-effectiveness of twice-daily indacaterol/glycopyrrolate inhalation powder for the treatment of moderate to severe COPD in the US.

BACKGROUND: Indacaterol 27.5 µg/glycopyrrolate 15.6 µg (IND/GLY 27.5/15.6 µg) inhalation powder, a twice-daily, fixed-dose combination of a long-acting beta2-agonist (LABA) and a long-acting antimuscarinic antagonist (LAMA), is indicated in the US for long-term maintenance treatment of airflow obstruction in patients with COPD. The safety and efficacy of IND/GLY 27.5/15.6 µg have been established, but cost-effectiveness is not yet known. This study compared the cost-effectiveness of IND/GLY 27.5/15.6 µg with other long-acting COPD maintenance therapies. METHODS: A Markov model was constructed from the US payer perspective. Health states were defined as mild (post-bronchodilator FEV1 ≥80% of predicted), moderate (50% ≤FEV1 <80% of predicted), severe (30% ≤FEV1 <50% of predicted), and very severe (FEV1 <30% of predicted) COPD. Patients entering the model transitioned through health states based on placebo-adjusted change from baseline in trough FEV1 for each comparator at week 12. Comparators included other US Food and Drug Administration-approved LABA/LAMA fixed-dose combinations as well as commonly prescribed LAMA and LABA/inhaled corticosteroid agents. One-way and probabilistic sensitivity analyses were conducted to test the model assumptions and the overall robustness of the results. RESULTS: Using the model, IND/GLY 27.5/15.6 µg treatment for 12 weeks resulted in total costs of US $23,375 vs US $9,365 for placebo. Compared with placebo, IND/GLY 27.5/15.6 treatment resulted in the highest improvement in FEV1 across all comparators and the lowest cost per decline in 100 mL FEV1. IND/GLY 27.5/15.6 µg was also among the most cost-effective treatment option as measured by St George's Respiratory Questionnaire response rate, at US $3,518 per additional responder at 12 weeks compared with placebo. In addition, IND/GLY 27.5/15.6 µg had the lowest cost per severe exacerbation avoided vs placebo across all comparators (US $87,686). CONCLUSION: This model, developed from the US payer perspective with a 5-year time horizon, found IND/GLY 27.5/15.6 µg to be a cost-effective treatment option for patients with moderate to severe COPD.

Cost-effectiveness of injectable disease-modifying therapies for the treatment of relapsing forms of multiple sclerosis in Spain.

OBJECTIVE: To compare the cost-effectiveness of injectable disease-modifying therapies (DMTs) for the first-line treatment of relapsing-remitting multiple sclerosis (RRMS) in Spain. METHODS: A Markov model was developed to estimate the cost-effectiveness of intramuscular interferon beta-1a (IM IFNß-1a), subcutaneous interferon beta-1a (SC IFNß-1a), interferon beta-1b (IFNß-1b) and glatiramer acetate (GA) relative to best supportive care in a hypothetical cohort of 1,000 RRMS patients in Spain. The model was developed from a societal perspective with a time horizon of 30 years. Natural history and clinical trial data were used to model relapse rates and disease progression. Cost and utility data were obtained from a published survey of multiple sclerosis patients in Spain. The primary outcome measure was cost per quality-adjusted life year (QALY) gained. Univariate and probabilistic sensitivity analyses were performed. RESULTS: Compared to best supportive care, the base case cost-effectiveness was 168,629 per QALY gained for IM IFNß-1a, 231,853 per QALY gained for IFNß-1b, 295,638 per QALY gained for SC IFNß-1a, and 318,818 per QALY gained for GA. Results were most sensitive to changes in DMT cost, utility values and treatment effect. CONCLUSIONS: In our cost-effectiveness analysis of first-line injectable DMTs in Spain, we found IM IFNß-1a to be more cost-effective than SC IFNß-1a, IFNß-1b or GA. Sensitivity analyses confirmed the robustness of these results.

The cost offsets and cost-effectiveness associated with pegylated drugs: a review of the literature.

Pegylation (PEG) is used as both a drug-delivery and a drug-modification technology in ten drugs approved by the US FDA. Benefits of PEG drugs can include increased plasma half-life, longer absorption, improved tumor targeting and less antigenicity and immunogenicity. Clinical benefits of PEG drugs over non-PEG drugs may include reduced administration, improved efficacy, improved tolerability, and decreased severity and incidence of adverse events. This study reviews 37 economic literature publications featuring PEG drugs versus non-PEG versions. PEG drugs showed some reductions in overall costs resulting from various offsets including fewer administrations, lower adverse event treatment costs, reduced disease complication costs or reduced inpatient/outpatient costs. Of the 18 cost-effectiveness studies reviewed, 17 of them found PEG drugs to be cost effective versus the non-PEG drugs. Cost offsets and cost-effectiveness of PEG drugs have been demonstrated in multiple studies across various therapies, indications and country settings, and the results have been found to be stable when key parameters were varied in analyses. Further studies are needed to assess the potential for cost savings and cost-effectiveness for new PEG therapies in development.

Effects of cohort selection on the results of cost-effectiveness analysis of disease-modifying drugs for relapsing-remitting multiple sclerosis.

BACKGROUND: Decision-analytic cost-effectiveness models are used to determine the most cost-effective treatment option on the basis of the best available data. Guidelines for pharmacoeconomic model development indicate that models should be updated as new evidence becomes available. OBJECTIVE: To evaluate the appropriateness of the clinical data that were selected for Goldberg et al.'s 2009 model of cost-effectiveness in multiple sclerosis and calculate results based on a revised cohort selection method for intramuscular (IM) interferon (IFN) beta-1a. METHODS: The original model compared cost per relapse avoided for IM IFN beta-1a, subcutaneous (SC) IFN beta-1a, IFN beta-1b, and glatiramer acetate (GA) based on intent-to-treat (ITT) results from clinical trials. However, due to lower-than-expected subject dropout rates, the IM IFN beta-1a trial had sufficient statistical power to be terminated early and was subsequently found to have met its primary endpoint, time to sustained 1.0-point Expanded Disability Status Scale progression. Within the "all-patient"(ITT) cohort (n=301), approximately 43% of patients were followed for less than 2 years; 172 patients were followed for 2 years or more. In contrast, the proportions of patients followed for at least 2 years in the clinical trials of IFN beta-1b, SC IFN beta-1a, and GA were 92%, 90%, and 86%, respectively. To test the impact of data selection on the cost-effectiveness model results, we recreated the original model using both the all-patient and 2-year cohorts from the IM IFN beta-1a pivotal trial. We then compared our results with those of the original model. RESULTS: In the original model, costs per relapse avoided were $141,721 for IM IFN beta-1a, $80,589 for SC IFN beta-1a, $87,061 for SC IFN beta-1b, and $88,310 for GA. In the reanalysis using the 2-year completer data for IM IFN beta-1a, costs per relapse avoided were $77,980 for IM IFN beta-1a, $80,121 for SC IFN beta-1a, $86,572 for IFN beta-1b, and $87,767 for GA. The cost per relapse avoided for IM IFN beta-1a was approximately 45% lower than in the original analysis, whereas the recreated results for the other 3 therapies differed from the original results by less than 1%. Sensitivity analyses showed that the recreated model was robust and that the rank order of cost-effectiveness results was unaffected by changes to any univariate parameter. CONCLUSIONS: The current study highlights the importance of data selection in cost-effectiveness analyses. After limiting the pivotal trial data for IM IFN beta-1a to patients followed for at least 2 years, we found that IM IFN beta-1a was more cost-effective than in the original analysis, while results for the other first-line disease-modifying drugs remained stable.

Payer costs in patients undergoing uterine artery embolization, hysterectomy, or myomectomy for treatment of uterine fibroids.

PURPOSE: To compare health resource use and medical costs in patients with uterine leiomyomas treated with hysterectomy, myomectomy, or uterine artery embolization (UAE). MATERIALS AND METHODS: Patients who underwent hysterectomy, myomectomy, or UAE for leiomyomas were identified from a nationally representative private payer claims database based on their diagnosis and procedure codes. The study included patients with no prior hysterectomy, myomectomy, or UAE and no previous diagnosis of gynecologic cancer. Health resource use and medical costs were evaluated over a period of 12 months. RESULTS: The study included 2,836 hysterectomy, 704 myomectomy, and 125 UAE patients. Average patient ages were 46 years for hysterectomy, 38 years for myomectomy, and 45 years for UAE (P < .001). Median UAE procedure costs were $5,968, compared with $7,299 for myomectomy (P = .031) and $7,707 for hysterectomy (P < .001). Median total 12-month payer costs were not significantly different among the three procedures ($10,519 for UAE vs $9,652 for myomectomy [P = .372] and $10,044 for hysterectomy [P = .813]). There were no differences in overall hospital admissions or emergency room visits after the procedures. Patients who underwent UAE had greater fibroid-related hospital and physician office use beyond 30 days after treatment (P < .001). During this period, 65.6% of patients treated with UAE had at least one imaging study, versus 37.1% of those treated with myomectomy (P < .001) and 14.1% of those treated with hysterectomy (P < .001). CONCLUSIONS: Procedure costs were significantly lower for UAE versus myomectomy and hysterectomy, but there was no difference in total 12-month payer costs. Postprocedural imaging appears to be a factor in total UAE costs. Further research is needed to better understand the role of imaging studies after UAE.