Roflumilast: Who Is Using It and How It Affects Health Care Resource Utilization and Costs.

OBJECTIVE: Compare baseline characteristics, health care resource utilization (HCRU), and associated costs of COPD patients treated with add-on roflumilast with those of other combination medications. DESIGN: Retrospective cohort study. METHODOLOGY: Patients aged 40 years with a diagnosis of chronic obstructive pulmonary disease (COPD) between March 1, 2011, and Nov. 30, 2012, were identified from the HealthCore Integrated Research Database and classified as roflumilast or nonroflumilast combination-therapy cohorts. Baseline characteristics were compared for all patients. HCRU and costs were compared between matched (M) roflumilast and nonroflumilast cohorts, using propensity score as a partial balancing score and then complementing the score with exact matching on specifically important variables. Generalized linear model and Poisson regression were used to estimate the adjusted differences in total costs and hospitalization rates, respectively, between the 2 matched cohorts. RESULTS: A total of 695 roflumilast and 30,542 nonroflumilast combination therapy users were identified. At baseline, the roflumilast cohort had more complex COPD and a higher number of severe and moderate COPD exacerbations relative to the nonroflumilast cohort. After matching, the roflumilast (M) and nonroflumilast (M) cohorts (n = 328 in each) had similar mean age, gender distribution, and follow-up time. The roflumilast (M) cohort had significantly higher pharmacy-related, per-patient, per-month (PPPM) costs (P < .001) and similar total cost (P = .90). After adjusting for confounding variables, no difference was observed between the 2 cohorts in total costs (P = .86) and number of hospitalizations (P = .65). CONCLUSION: Findings suggest that patients in the roflumilast cohort, relative to the nonroflumilast cohort, were more severely ill in the real-world setting. Despite higher pharmacy costs, the total cost for the roflumilast cohort was statistically similar to the nonroflumilast cohort. Future studies with longer follow-up are needed to evaluate the long-term economic impact of roflumilast use.

Changes in Patterns of Utilization and Cost of Health Care Services Associated With Initiation of Asenapine for the Treatment of Schizophrenia in Adults.

PURPOSE: To examine changes in patterns of utilization and cost of health care services associated with initiation of asenapine for the treatment of schizophrenia in adults. DESIGN: Retrospective cohort study using 2 large US health care claims databases. METHODOLOGY: All adults who initiated therapy with asenapine between Aug. 1, 2009, and Dec. 31, 2012, were identified; the date of the earliest claim for asenapine during this period was deemed the index date. Patients without ≥1 claims with a schizophrenia diagnosis within 12 months prior to the index date were excluded. We compared patterns of utilization and cost of health care services between 6-month periods immediately before and after index date ("preindex"and "postindex" respectively). RESULTS: 366 patients were identified who initiated asenapine and who met all other selection criteria; mean (SD) age was 40.5 (16.3) years and 57.1% were women. Relative to preindex, patients were less likely during postindex to be hospitalized (41.8% vs 26.2%, P<.001) or to visit the emergency room (24.9% vs 18.9%, P=.03). Mean (SD) total health care costs decreased by $4776 in the postindex period ($16,811 [$26,176] vs $12,035 [$17,037] during preindex), primarily due to a decrease in inpatient costs ($10,616 [$24,977] vs $5286 [$15,846]); mean pharmacy costs increased by $828 ($3656 [$3309] vs $4482 [$3,073]) (all P<.001). CONCLUSION: Use of asenapine for the treatment of schizophrenia was associated with reduced levels of health care utilization and cost during the 6-month period immediately following therapy initiation, primarily due to reduced levels of inpatient care.

Microsimulation to compare activity-related bleed risks between pharmacokinetic-guided rurioctocog alfa pegol prophylaxis and emicizumab.

BACKGROUND: Owing to a lack of clinical study data, computational modeling was used to estimate activity-related bleed risk during prophylaxis with either rurioctocog alfa pegol or emicizumab. RESEARCH DESIGN AND METHODS: A pharmacokinetic (PK)-based computational model was used to estimate factor VIII (FVIII) levels for individual patients in the PROPEL study who were treated with PK-guided rurioctocog alfa pegol prophylaxis targeting FVIII trough levels of 1-3% or 8-12%. Emicizumab was assumed to have 20% FVIII equivalency. Six hypothetical patient activity profiles were created using the National Hemophilia Foundation's physical activity risk ratings scale. For each profile and treatment regimen combination, the total bleed risk over a 2-week period was estimated relative to a patient who was participating in a low-risk activity with 0% FVIII, and the overall relative bleed risks were compared. RESULTS: For all evaluated activity profiles, rurioctocog alfa pegol prophylaxis targeting either 1-3% or 8-12% FVIII trough levels was associated with a lower estimated bleed risk compared with emicizumab prophylaxis with assumed 20% FVIII equivalency (P < 0.001). CONCLUSION: Although this model does not reflect actual patient outcomes, it suggests that PK-guided rurioctocog alfa pegol prophylaxis may reduce the bleed risk during physical activities.

Burden of Illness and Treatment Patterns Among Patients With von Willebrand Disease in US Clinical Practice.

In this retrospective cohort study, data from an integrated US healthcare system containing both electronic medical record data and linked claims data (from 01/2004 to 12/2020) were used to evaluate the clinical burden, treatment patterns, and healthcare resource use (HRU) in patients with von Willebrand disease (VWD). Two patient cohorts were analyzed: the overall VWD population (n = 396) and a subset of these patients (n = 75) who were considered potentially eligible for prophylaxis treatment with von Willebrand factor (VWF) based on a history of severe and frequent bleeding. HRU (hospitalizations, outpatient visits, and emergency department visits) were measured in patients with linked claims data (n = 110, overall VWD patients; n = 23 potentially VWF-prophylaxis-eligible VWD patients). In general, patients with VWD experienced a substantial burden of bleeding events, comorbidities, and HRU. Patients with VWD who were considered potentially eligible for prophylaxis owing to severe and frequent bleeds suffered from a higher clinical burden and HRU than the overall VWD population, and thus may benefit from VWF prophylactic treatment. The findings from this study could help improve clinical outcomes and manage HRU for patients with VWD.

Outcomes in Patients With von Willebrand Disease Receiving Recombinant von Willebrand Factor on Demand and in Surgical Settings: Chart Review.

This European observational chart review assessed the efficacy/safety of recombinant von Willebrand factor (rVWF) for on-demand treatment of spontaneous/traumatic bleeds and prevention and/or treatment of surgery-related bleeding in adults with von Willebrand disease (VWD). Patients (n = 91) were enrolled at first rVWF administration (index). Data were collected for the 12 months before index and until death, loss to follow-up, or end of study (3-12 months after index). Fifteen patients reported an rVWF-treated spontaneous/traumatic bleed at index. Bleed resolution was obtained for 14 patients (unknown status, n = 1), and investigators assessed treatment satisfaction for 13 rVWF prescriptions (2 moderate, 5 good, and 6 excellent). rVWF was used to prevent/treat surgery-related bleeds at index in 76 patients. Bleed resolution was achieved in 25/58 rVWF-treated surgeries; bleed resolution was not applicable for 33 surgeries. In both groups, there were no reports of treatment-emergent adverse events after initiating rVWF, including hypersensitivity reactions, thrombotic events, and VWF inhibitor development. rVWF was shown to be effective for the on-demand treatment of spontaneous/traumatic bleeds, and for the prevention and treatment of surgical bleeds in this real-world VWD population.

Comparison of Real-World Dose and Consumption for Two Extended Half-Life Recombinant Factor VIII Products for the Treatment of Hemophilia A in the United States.

Background: US patients with hemophilia A can receive prophylaxis with extended half-life recombinant factor VIII (rFVIII) products, including efmoroctocog alfa (fragment crystallizable fusion protein) and rurioctocog alfa pegol (antihemophilic factor [recombinant], PEGylated). Objective: To evaluate dosing patterns and weekly consumption of extended half-life rFVIII products in the United States. Methods: We performed a retrospective analysis using the US Specialty Pharmacy Database (2015-2018). Included patients had a diagnosis of hemophilia A, ≥2 consecutive monthly claims for efmoroctocog alfa or rurioctocog alfa pegol for prophylaxis, and weight data. Outcome measures included weekly dosing frequency and dispensed weekly dose. Results: The analysis included 774 patients (efmoroctocog alfa, 506; rurioctocog alfa pegol, 268). Mean (SD) age was 24.2 (15.8) and 26.3 (14.9) years for patients receiving efmoroctocog alfa and rurioctocog alfa pegol, respectively; mean (SD) weight was 68.4 (36.8) and 79.8 (37.7) kg, respectively. The most frequent efmoroctocog alfa regimen was twice weekly (45.7%), followed by every 4 days (20.6%), every 3 days (9.1%), and 3 times per week (7.5%). The most frequent rurioctocog alfa pegol regimen was twice weekly (72.4%), followed by 3 times per week (8.7%), every 4 days (7.6%), and every 3 days (5.5%). The proportion of efmoroctocog alfa twice-weekly dispensing records increased from 31.5% to 50.9%, and every 4 days dispensing records decreased from 31.3% to 14.5% (2015-2018). The proportion of rurioctocog alfa pegol dispensing records remained broadly stable (2016-2018). Overall, mean (SD; median) weekly prophylactic dose was 105.4 (77.9; 92.6) IU/kg with efmoroctocog alfa, and 96.8 (41.9; 90.9) IU/kg with rurioctocog alfa pegol. Conclusion: In this database study, the most frequently observed dosing frequency was twice weekly for patients receiving efmoroctocog alfa or rurioctocog alfa pegol. The observed mean weekly consumption was slightly higher, and variation was greater, in patients receiving efmoroctocog alfa versus rurioctocog alfa pegol.

Disease Burden in Patients with von Willebrand Disease Potentially Eligible for Prophylaxis: Post Hoc Analysis of a European Cross-Sectional Study.

Recent international guidelines conditionally recommend von Willebrand factor (VWF) prophylaxis for von Willebrand disease (VWD) patients with a history of severe/frequent bleeds. This post hoc analysis of the Cost of VWD Across Europe, a Socioeconomic Study (CVESS; conducted in 2018), assessed patient characteristics and disease burden in patients aged >1 year with congenital VWD not receiving but potentially eligible for prophylaxis based on severe/frequent bleeds, and those receiving prophylaxis in the previous 12 months. Data were collected using medical records and a patient questionnaire. Patients considered potentially prophylaxis-eligible (n = 102) experienced more bleeds than patients receiving prophylaxis (n = 229) and were more likely to be admitted to the hospital due to bleeding events in the prior 12 months. Quality of life and work productivity were similar between the two groups. Logistic regression analysis showed that the prophylaxis-eligible group was more likely to have poor joint function and moderate chronic pain than the prophylaxis group. This retrospective study suggests that 1/7 patients not receiving VWF prophylaxis had a higher disease burden than patients receiving prophylaxis and would potentially benefit from prophylaxis.

The Impact of Pharmacokinetic-Guided Prophylaxis on Clinical Outcomes and Healthcare Resource Utilization in Hemophilia A Patients: Real-World Evidence from the CHESS II Study.

Background: Using a pharmacokinetic (PK)-guided approach to personalize the dose and frequency of prophylactic treatment can help achieve and maintain targeted factor VIII (FVIII) trough levels in patients with hemophilia A. Objective: Investigate clinical and healthcare resource use outcomes in patients with hemophilia A treated with or without PK-guided prophylaxis using data from the Cost of Haemophilia in Europe: A Socioeconomic Survey (CHESS) II database. Methods: CHESS II was a cross-sectional, retrospective, burden-of-illness study incorporating data from eight European countries. Patients were eligible for this analysis if they were male, ≥18 years of age, and diagnosed with congenital hemophilia A of any severity. The clinical endpoints included annualized bleeding rate (ABR), presence and number of problem/target joints, and occurrence of joint surgeries. Healthcare resource utilization endpoints included the number of hematologist consultations and bleed-related hospitalizations or emergency department admissions. Data from November 2018 to October 2020 were included and were stratified according to treatment regimen and use of PK-guided dosing. Results: Altogether, 281 patients on prophylaxis had available FVIII trough level data. Mean (SD) age was 35.7 (13.8) years. A specific FVIII trough level was targeted in 120 (42.7%) patients and 47 (39.2%) received PK-guided dosing. Patients receiving PK-guided dosing had a mean (SD) ABR of 2.8 (2.1) and target joint number of 0.5 (0.7), compared with 3.9 (2.7) and 0.9 (1.4), respectively, for patients receiving non-PK-guided treatment. The mean (SD) number of hematologist consultations was 7.1 (5.3) for patients receiving PK-guided dosing versus 10.7 (5.7) for those who were not. A higher proportion of patients in the non-PK-guided group required hospitalization during their lifetime compared with the PK-guided group. Conclusion: This analysis of real-world data suggests that PK-guided dosing for prophylaxis has a beneficial impact on clinical and healthcare resource utilization outcomes in patients with hemophilia A.

Real-world study of rurioctocog alfa pegol and emicizumab in US clinical practice among patients with hemophilia A.

BACKGROUND: FVIII replacement is standard treatment for hemophilia A without inhibitors, but non-factor therapies, such as emicizumab, are changing the treatment landscape. We explore the ramifications of switching treatment. METHODS: Pharmacy database data (July 2017-May 2020) from patients with hemophilia A without inhibitors who switched to rurioctocog alfa pegol or emicizumab prophylaxis after ≥6 months' prophylaxis with another FVIII product were analyzed for total mean weekly consumption, dosing frequency, product wastage, and ABR. RESULTS: Post-switch mean weekly consumption of prophylactic rurioctocog alfa pegol and emicizumab were 6224 IU/kg and 109 mg, respectively. Dosing schedules for emicizumab were primarily weekly (48.2%) and every 2 weeks (40.0%). Most patients in the rurioctocog alfa pegol cohort received treatment twice-weekly (83.3%). Mean product wastage of emicizumab (8.4%) was significantly higher versus rurioctocog alfa pegol (-0.3%; P < 0.001). Mean annualized emicizumab and rurioctocog alfa pegol wastage during prophylaxis was 330.82 mg and -974.80 IU, respectively. ABR change was not significantly different (P = 0.527) for patients switching to emicizumab (-1.05) or rurioctocog alfa pegol (-1.53). CONCLUSIONS: Bleed rates were similar for patients receiving prophylaxis with emicizumab or rurioctocog alfa pegol after switching from prophylaxis with another FVIII. However, wastage associated with dispensing inaccuracies was greater with emicizumab.

Recent advances in therapeutic options for rare hemostatic disorders: selected poster extracts of recent research in hemophilia A, congenital hemophilia with inhibitors, von Willebrand disease, and thrombotic thrombocytopenic purpura presented at the 29th congress of the International Society on Thrombosis and Haemostasis (ISTH 2021, Jul 17-21; virtual congress).

Hemophilia, von Willebrand disease (VWD), and thrombotic thrombocytopenic purpura (TTP) are rare diseases affecting normal hemostasis. Although they differ in their pathogenesis and clinical manifestation, if left undiagnosed and untreated, all these conditions can result in severe long-term consequences and can be potentially life-threatening. This article summarizes a poster series funded by Takeda and presented virtually at the 29th annual congress of the International Society on Thrombosis and Haemostasis (ISTH) in 2021: Data from real-world evidence highlight the importance of joint health and personalized prophylaxis to prevent bleeding for patients with hemophilia, the need to further raise disease awareness in support of timely diagnosis and access to treatment in general practice settings for patients with VWD, and describe the clinical burden for patients with TTP and the importance to advance treatment options for these patients.

Impact of chronic constipation on health-related quality of life, work productivity, and healthcare resource use: an analysis of the National Health and Wellness Survey.

BACKGROUND: There has been limited research addressing the effects of constipation on work productivity and healthcare resource use. AIMS: To assess the effect of chronic constipation on health outcomes and healthcare resource use. METHODS: Using data from the 2007 National Health and Wellness Survey (NHWS), chronic constipation patients (n = 1,430) were propensity score-matched to controls (n = 1,430) on demographic and clinical characteristics. Differences between groups in health-related quality of life (SF-12v2), work productivity and activity impairment, and resource use in the last 6 months were examined. Mediation analyses were conducted in order to determine whether the relationship between constipation and resource use was caused by a reduction in health status. RESULTS: Chronic constipation patients reported significantly lower levels of health-related quality of life (physical component summary score: 39.57 vs. 43.73; mental component summary score: 43.19 vs. 47.86, all P-values < 0.01) and significantly higher levels of loss of work productivity and activity impairment (absenteeism: 9.08% vs. 5.20%; presenteeism: 29.52% vs. 19.09%; overall work impairment: 33.65% vs. 21.56%; activity impairment: 46.58% vs. 33.90%, all P-values < 0.01) compared to the matched controls. Chronic constipation patients also reported significantly more provider (7.73 vs. 5.63) and emergency room visits (0.52 vs. 0.30) in the past 6 months (all P-values < 0.01). Mediation analyses suggested that increased resource use among chronic constipation patients were partially a result of reduced health status. CONCLUSIONS: Compared to matched controls, chronic constipation patients reported greater economic and humanistic burden. Alleviating the humanistic burden associated with constipation may have economic benefits.

Reslizumab Compared with Benralizumab in Patients with Eosinophilic Asthma: A Systematic Literature Review and Network Meta-Analysis.

BACKGROUND: The interaction of IL-5 with its receptor on eosinophils increases the activation and maintenance of eosinophils; blocking this interaction reduces asthma symptoms in patients with the eosinophilic phenotype. Reslizumab, which binds to IL-5, and benralizumab, which targets the IL-5 receptor α subunit, have not been compared in head-to-head trials. OBJECTIVE: To indirectly compare reslizumab with benralizumab in similar patient populations using a network meta-analysis. METHODS: A systematic literature review was conducted and a network meta-analysis was performed on eligible studies using the Markov Chain Monte-Carlo simulation method and a Bayesian statistical framework. RESULTS: Eleven studies were identified, 4 of which evaluated clinically relevant doses and had outcomes at similar time points. To control for population differences, subgroups were selected for the base-case efficacy analysis: a benralizumab subgroup with blood eosinophil levels of greater than or equal to 300 cells/µL (n = 1537) and a reslizumab subgroup in Global Initiative for Asthma step 4/5 with 2 or more previous exacerbations and greater than or equal to 400 eosinophils/µL (n = 318). Safety was analyzed in the full population (N = 3462). Reslizumab significantly improved Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) scores compared with benralizumab once every 4 weeks and there were reasonably high posterior probabilities that reslizumab is superior to benralizumab once every 4 weeks and once every 8 weeks for ACQ score, AQLQ score, FEV1, and clinical asthma exacerbations. CONCLUSIONS: This indirect comparison suggests that reslizumab may be more efficacious than benralizumab in patients with eosinophilic asthma in Global Initiative for Asthma step 4/5 with elevated blood eosinophil levels (benralizumab, ≥300/µL; reslizumab, ≥400/µL) and 2 or more exacerbations in the previous year.

Reslizumab and mepolizumab for moderate-to-severe poorly controlled asthma: an indirect comparison meta-analysis.

Aim: A systematic literature review and network meta-analysis assessed the efficacy and safety of reslizumab 3.0 mg/kg and mepolizumab 100 mg. Materials & methods: Eligible studies evaluated reslizumab and mepolizumab in patients with inadequately-controlled severe eosinophilic asthma. Using a Bayesian network meta-analysis, 95% credible intervals and posterior probabilities were reported. Results: Of 19 indirect efficacy comparisons performed in base-case (Global Initiative for Asthma 4/5 patients with ≥2 exacerbations in the previous year) and overall populations, significant differences favoring reslizumab were observed for severe exacerbations, FEV1 at 4 weeks and eosinophil counts at 4, 16 and 24 weeks, with no other significant differences including risk of adverse events. Conclusion: Indirect comparison of reslizumab and mepolizumab largely showed no significant differences in efficacy or safety.

The impact of the Medicare Part D prescription benefit on generic drug use.

BACKGROUND: Little information exists regarding the impact of Medicare Part D on generic drug use. OBJECTIVE: To examine changes in the use of generic prescriptions attributable to Part D among a sample of Medicare beneficiaries. DESIGN, PARTICIPANTS, AND MEASUREMENTS: Difference-in-difference analysis of pharmacy claims of Part D enrollees and non-enrollees aged 67-79 years from 2005 to 2006. The final sample represented approximately 2.4 million unique subjects. Analyses were conducted separately for major therapeutic classes, limited to subjects filling at least one prescription within the class during 2005 and 2006, and adjusted for subject characteristics, prescription characteristics, socio-demographic characteristics measured through zipcode-linked Census data, baseline differences between Part D and non-Part D enrollees, and secular trends in generic use. RESULTS: Generic drugs accounted for 58% of total prescriptions. Among the entire group of beneficiaries, there was a trend of increased generic drug use in 13 out of 15 drug classes examined. However, after adjusting for potential confounders, the growth rate of generic drug use was lower among Part D enrollees than among non-enrollees; enrollees were slightly less likely to fill prescriptions for generic drugs vs. brand-name drugs in 2006 compared to 2005 (odds ratio 0.95, 95% confidence interval 0.94-0.95). CONCLUSIONS: Despite secular trends of increased utilization of generic drugs among both Part D enrollees and non-enrollees, the net impact of Part D among these beneficiaries was a modest decrease in the use of generic drugs. This finding, which is consistent with economic theory but contrary to several recent reports, highlights the complexity of assessing the impact of Part D on overall consumer welfare.

The Medicare Part D doughnut hole: effect on pharmacy utilization.

The Medicare Prescription Drug Improvement and Modernization Act of 2003 offers prescription drug coverage through the Medicare part D program. However, the standard benefit does include a gap in coverage, commonly known as the "doughnut hole". This study, which included 90,615 subjects, aimed to evaluate the effect of the prescription drug coverage gap on drug utilization and expenditures. Beneficiaries in the study group were older (76.34 vs. 73.04 yr, P < .0001) and sicker (5.39 vs. 3.66 disease conditions, P < .0001) than those in the control group. They also incurred substantially higher out-of-pocket expenses ($2534 vs. $598, P < .0001) than the individuals in the control group. From the preperiod to the postperiod, the study group's average days of therapy decreased by 15.85% (from 1104 to 929, P < .0001), and total costs fell 28.02% (from $2441 to $1757, P < .0001). The average out-of-pocket costs increased by 88.94% (from $877 to $1657, P < .0001); in the control group, however, the average days of therapy increased by 1.77% (from 680 to 692), and total costs rose by 2.19% (from $1322 to $1351). Out-of-pocket costs decreased by 5.54% ($307 to $290). Using difference-indifference models, the Medicare part D prescription drug coverage gap was estimated to have reduced medication utilization by 187.49 days of therapy (P < .0001) while raising out-of-pocket costs by $796.49 (P < .0001) and increasing the generic utilization rate by 7.33% (P < .0001). Regular Medicare part D beneficiaries reduced medication utilization after they reached the coverage gap, which raises concerns those beneficiaries may face an increased risk of adverse health events.

Stratification of eosinophilic asthma patients treated with reslizumab and GINA Step 4 or 5 therapy.

Reslizumab, an anti-interleukin-5 monoclonal antibody, significantly reduces exacerbation frequency and improves lung function, asthma control and quality of life in adults with severe eosinophilic asthma, as demonstrated in Phase III studies. This secondary analysis assessed reslizumab's efficacy in patients receiving baseline treatment per Global Initiative for Asthma (GINA) Step 4 and Step 5 guidelines. Pooled data from duplicate, Phase III, reslizumab versus placebo studies in patients with severe eosinophilic asthma (blood eosinophils ≥400 cells·µL-1) were stratified by baseline therapy. Efficacy assessments were exacerbation rates and changes from baseline forced expiratory volume in 1 s (FEV1) and patient-reported outcomes. Of 953 patients, 69% (n=657) and 11% (n=106) were receiving Step 4 and Step 5 therapy, respectively. Compared with placebo, reslizumab reduced exacerbation rates by 53% (95% CI 0.36-0.62) and 72% (95% CI 0.15-0.52), in Step 4 and Step 5 groups respectively. By study end, reslizumab increased FEV1 in Step 4 and Step 5 groups by 103 mL (95% CI 52-154 mL) and 237 mL (95% CI 68-407 mL), respectively. Reslizumab also improved patient-reported outcomes compared with placebo in both groups. Reslizumab reduces exacerbation rates and improves lung function and patient-reported outcomes in patients with eosinophilic asthma receiving therapy per Steps 4 and 5 of the GINA guidelines.

Clinical and Economic Burden of Elevated Blood Eosinophils in Patients With and Without Uncontrolled Asthma.

BACKGROUND: The European Respiratory Society and American Thoracic Society (ERS/ATS) published guidelines in 2014 for the evaluation and treatment of asthma. These guidelines draw attention to management of patients with asthma that remains uncontrolled despite therapy. One phenotypic characteristic of therapy-resistant asthma is eosinophil elevation. It is important to better understand the burden of care gaps in this patient subgroup in order to support improved treatment strategies in the future. OBJECTIVE: To quantify the economic burden of asthma patients with and without peripheral blood eosinophil elevation. METHODS: A retrospective cohort study was conducted using data from patients aged 12 years or older with a diagnosis of asthma using electronic health records of over 2 million patients between 2004-2010. Patients with a diagnosis of chronic obstructive pulmonary disease, Churg Strauss syndrome/Wegener's granulomatosis, eosinophilia, cystic/pulmonary fibrosis, allergic bronchopulmonary aspergillosis, or lung cancer in the 12-month period before the date of asthma diagnosis were excluded. Patients with asthma were followed for 12 months after their initial asthma diagnosis to identify those with controlled versus uncontrolled asthma based on ERS/ATS criteria. Patients with at least 1 peripheral blood eosinophil test result of ≥ 400 cells/µL were classified as those with elevated eosinophils. Total annual paid-claim cost was compared by eosinophil levels within the controlled and uncontrolled asthma subgroups. Costs were adjusted to 2015 U.S. dollars. Patients were stratified by control level, and generalized linear modeling regressions were used to assess the magnitude of increase in cost of the elevated eosinophil group. RESULTS: A total of 2,701 patients were included in the study, of which 17% had uncontrolled asthma and 21% had elevated eosinophils. The mean total annual cost of patients with uncontrolled asthma was more than 2 times the cost of those with controlled asthma ($18,341 vs. $8,670, P < 0.001). Patients with uncontrolled asthma in the elevated eosinophil group had almost double the total cost ($28,644 vs. $14,188, P = 0.008) compared with those with blood eosinophil levels in a normal range. Similarly, patients classified as those with controlled asthma in the elevated eosinophil group had almost twice the average costs as those without elevated eosinophils ($14,754 vs. $7,203, P < 0.001). Uncontrolled asthma with elevated eosinophils had 4 times greater hospital admissions and over 4 times higher total costs than controlled asthma without elevated eosinophils. Among patients with uncontrolled asthma, patients with elevated eosinophils had a 53% increase in mean cost ($17,723 vs. $11,581, P < 0.001) compared with patients without elevated eosinophils. Among patients with controlled asthma, patients with elevated eosinophils had a 62% increase in mean cost ($8,897 vs. $5,486, P < 0.001) compared with patients without elevated eosinophils. CONCLUSIONS: Elevated peripheral blood eosinophil level is associated with higher cost irrespective of disease control status. DISCLOSURES: This study was funded by Teva Pharmaceuticals. Dotiwala and Casciano report consulting and writing fees from Teva Pharmaceuticals for work on this study. Sun is an employee and stockholder of Teva Pharmaceuticals. Li reports consulting fees from eMAX Health. All authors contributed to study design. Dotiwala took the lead in data collection, along with the other authors, and data interpretation was performed primarily by Krishnan, Sun, and Li, along with Casciano and Dotiwala. The manuscript was written by Casciano, Dotiwala, and Li, along with Sun and Krishnan, and revised by Casciano, Dotiwala, Sun, and Li, with assistance from Krishnan.

Benefits of Early Roflumilast Treatment After Hospital or Emergency Department Discharge for a COPD Exacerbation.

BACKGROUND: Chronic lower respiratory disease, which includes chronic obstructive pulmonary disease (COPD), is the third leading cause of death in the United States. Roflumilast is an oral, once-daily, selective phosphodiesterase-4 inhibitor approved for reducing the risk for COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. OBJECTIVES: To evaluate the effects of roflumilast treatment timing on COPD exacerbation rates (primary objective) and on resource utilization and healthcare costs (secondary objective) after hospital or emergency department discharge associated with a COPD exacerbation. METHODS: In this retrospective cohort study, claims data from March 2011 to March 2013 were extracted from Truven Health MarketScan combined commercial healthcare claims and Medicare supplemental claims databases and were analyzed to compare the exacerbation rates and the healthcare resource utilization and costs between the early roflumilast treatment (treatment initiation ≤30 days after hospital or emergency department discharge) and the delayed roflumilast treatment (treatment initiation 31-180 days after discharge) cohorts. Multivariate logistic regression and generalized linear models with log-link function and gamma distribution were adjusted for age, sex, insurance plan type, COPD disease complexity, and comorbidities. RESULTS: A total of 995 patients (N = 280 early roflumilast treatment, N = 715 delayed roflumilast treatment) were included. Compared with the delayed roflumilast treatment group, patients in the early roflumilast treatment group were 39% less likely to have an exacerbation after hospital discharge (P = .004). The patients receiving early roflumilast treatment also had 42% (P = .003) and 37% (P = .005) lower risks for COPD-related and all-cause rehospitalizations, respectively, than patients in the delayed roflumilast treatment group. Significantly fewer patients receiving early roflumilast treatment had moderate (P = .013) or severe (P = .002) exacerbations. Early roflumilast treatment also was associated with reduced annualized COPD-related (P = .012) and all-cause (P = .009) rehospitalizations, outpatient visits per patient (P <.001 for COPD-related and all-cause), and procedures or therapies (COPD-related, P = .016; all-cause, P = .009). The early treatment group had fewer COPD-related emergency department visits per patient than the delayed roflumilast treatment group (P = .035), and the total mean annualized COPD-related and all-cause costs were reduced by $7273 (P = .014) and $14,111 (P = .002), respectively. Multivariate analyses showed that early treatment was associated with lower COPD-related and all-cause annualized health services costs per patient annually (P <.001 for both). CONCLUSION: In this real-world study, the patients with COPD who initiated roflumilast treatment ≤30 days after a hospital or emergency department discharge for a COPD-related exacerbation experienced fewer subsequent exacerbations and rehospitalizations, reduced healthcare utilizations, and lower healthcare costs than the patients who delayed their roflumilast treatment.

Choice of atypical antipsychotic therapy for patients with schizophrenia: An analysis of a medicaid population.

BACKGROUND: In patients treated at Veterans Affairs facilities, demographicand clinical characteristics have been found to influence the choice of atypical antipsychotic drugs. However, little is known about the influences on the choice between olanzapine and risperidone in patients with schizophrenia enrolled in Medicaid. OBJECTIVE: The aim of this study was to determine whether demographicand/or clinical characteristics and/or medical-service utilization before treatment were related to the choice of olanzapine versus risperidone therapy using data from a Medicaid population with schizophrenia. METHODS: The study sample was identified in the North Carolina (NC)Medicaid claims database. Data were included from patients aged 18 to 64 years who were diagnosed with schizophrenia; had initiated treatment with olanzapine or risperidone between July 1, 1998, and October 31, 2000; had not used atypical antipsychotics during the 6 months before the start of treatment; and were continuously eligible in the NC Medicaid program during the 6 months before the start of treatment. Multivariate logistic regression models were used to estimate the likelihood of the choice of olanzapine or risperidone associated with patients' demographic and clinical characteristics and medical-service utilization during the 6 months before the initiation of treatment. RESULTS: A total of 764 patients (383 women, 381 men; mean age, 42.1 years)were included in the analysis: 420 were initially prescribed olanzapine and 344 were prescribed risperidone. Men were more likely than women to be prescribed olanzapine compared with risperidone. Patients who had a hospitalization related to a psychiatric condition during the pretreatment period were more likely to be prescribed olanzapine compared with risperidone (OR = 1.530; P = 0.043). Significant regional variation in the likelihood of prescribing olanzapine or risperidone was found, with patients being prescribed risperidone at a higher rate compared with olanzapine in 2 counties with the largest schizophrenic populations. CONCLUSIONS: In this study of data from patients with schizophrenia identified in the NC Medicaid claims database, sex, a history of psychiatric-related hospitalization, and geographic residence were found to be correlated with the selection of treatment with olanzapine versus risperidone. These findings need to be confirmed in large, randomized, prospective studies.

Lower 30-day readmission rates with roflumilast treatment among patients hospitalized for chronic obstructive pulmonary disease.

BACKGROUND: Few data exist related to the impact of roflumilast on health care utilization. This retrospective study estimated 30-day hospital readmission rates between patients who did and did not use roflumilast among those with COPD hospitalizations. METHODS: Data were from MarketScan, a large US commercial health insurance claims database. Patients aged ≥40 years with at least one hospitalization for COPD between 2010 and 2011 were included. The roflumilast group included patients who used roflumilast within 14 days after the first hospitalization (index), while the comparison group (non-roflumilast) included patients who did not use roflumilast during the study period. Continuous enrollment for at least 6 months before and 30 days after the index date was required. The 30-day hospitalization rate was calculated after the index hospitalization. Conditional logistic regression with propensity score 1:3 matching was employed to assess the difference in 30-day hospital readmission rates between the roflumilast and non-roflumilast groups, adjusting for baseline characteristics, comorbidity, health care utilization, and COPD medication use within 14 days after the index date. RESULTS: A total of 15,755 COPD patients met the selection criteria, ie, 366 (2.3%) in the roflumilast group and 15,389 (97.7%) in the non-roflumilast group. The mean (± standard deviation) age was 71±12.5 years and 52% were female. After propensity score matching, all-cause 30-day hospitalization rates were 6.9% and 11.1% in the roflumilast and non-roflumilast groups, respectively. COPD-related 30-day hospitalization rates were 6.3% and 9.2% in the roflumilast and non-roflumilast groups, respectively. Conditional logistic regression identified a significantly lower likelihood of all-cause 30-day readmission (odds ratio 0.59, 95% confidence interval 0.37-0.93, P=0.023) for roflumilast patients relative to non-roflumilast patients. CONCLUSION: This study showed, in a real-world setting, that use of roflumilast was associated with a lower rate of hospital readmission within 30 days among patients hospitalized for COPD.