Adding tiotropium or long-acting ß2-agonists to inhaled corticosteroids: Asthma-related exacerbation risk and healthcare resource utilization.

Background: Based on current clinical guidelines, long-acting ß2-agonists (LABA) are frequently prescribed before long-acting muscarinic antagonists (LAMA) as an add-on to inhaled corticosteroids (ICS) in uncontrolled asthma. However, there is insufficient real-world evidence that supports this therapeutic approach. Objective: The objective was to compare asthma exacerbations and healthcare resource utilization in patients with asthma using the LAMA tiotropium bromide (Tio) or a LABA as an add-on to ICS (ICS + Tio or ICS/LABA) in a real-world setting. Methods: This retrospective, observational study included patients aged ≥12 years with asthma diagnoses identified in a U.S. longitudinal claims database (October 2015 to August 2020). The ICS + Tio and ICS/LABA cohorts were 1:2 propensity score matched for baseline variables. Outcomes were compared in the postmatched cohorts, and the risk of exacerbation was evaluated by using Kaplan-Meier curves. Results: After propensity score matching, there were 633 and 1266 patients in the ICS + Tio and ICS/LABA cohorts, respectively. The proportion of patients who experienced a severe or a moderate-or-severe exacerbation during follow-up was similar between the ICS + Tio versus ICS/LABA cohorts (4% versus 3%, p = 0.472, and 50% versus 45%, p = 0.050, respectively). The mean time to first severe (ICS + Tio 43.8 days versus ICS/LABA 49.4 days, p = 0.758) and moderate-or-severe exacerbation (ICS + Tio 65.8 days versus ICS/LABA 58.9 days, p = 0.474) was not statistically different between cohorts. The treatments had no effect on the risk of severe exacerbation, although it was 36% lower in ICS + Tio users than in ICS/LABA users (hazard ratio 0.64 [95% confidence interval, 0.22-1.84]). All-cause and asthma-related average monthly healthcare resource utilization were comparable between the treatments for hospitalizations and emergency department visits but were significantly greater in the ICS + Tio cohort than in the ICS/LABA cohort for asthma-related outpatient visits (p < 0.0001). Conclusion: This study provides real-world evidence that ICS + Tio may be a valid alternative when ICS/LABA cannot be used as first-line treatment for asthma maintenance therapy.

Assessment of Real-World Escalation to Biologics in US Patients With Asthma.

BACKGROUND: Previous studies indicate that suboptimal medication adherence may contribute to uncontrolled asthma. Global Initiative for Asthma (GINA) guidelines recommend treatment escalation to biologics for patients with uncontrolled asthma despite adherence to high-dose maintenance medication and who have eosinophilic/allergic biomarkers or require maintenance oral corticosteroids. OBJECTIVE: This study aimed to describe the clinical status of patients with asthma escalated to biologic therapy. METHODS: This retrospective claims database analysis enrolled US patients with asthma who were escalated to biologics between January 2016 and June 2020. Exacerbations, control status, GINA step, and maintenance medication adherence during the 12 months before biologic therapy initiation were analyzed. Asthma control was assessed using both the European Respiratory Society/American Thoracic Society (ERS/ATS) and Stempel criteria. Adherence was defined as the proportion of days covered (PDC) by maintenance medication claims. RESULTS: Of 1786 patients escalated to biologics, 506 were included for analysis. During the 12 months before escalation, 346 patients had confirmed exacerbations. Uncontrolled asthma status was estimated in 55% and 70% of patients (ERS/ATS and Stempel criteria, respectively). GINA step was inferred for 395 patients: 154 were at step 2, 11 at step 3, 104 at step 4, and 126 at step 5. Of 403 patients with maintenance medication claims, 63% had suboptimal maintenance medication adherence (PDC <80%). CONCLUSION: In this study, most patients initiating biologic therapy had mild-to-moderate asthma or suboptimal maintenance medication adherence, possibly indicating inappropriate escalation. Incorporating objective medication adherence monitoring into existing guidelines may reduce inappropriate escalation to biologics.

Real-world impact of fremanezumab on migraine symptoms and resource utilization in the United States.

BACKGROUND: Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for migraine prevention in adults. Real-world data on the effectiveness of fremanezumab are limited. This retrospective, observational cohort study assessed patient-reported migraine symptoms, health care resource utilization (HCRU), and direct medical costs before and after fremanezumab treatment initiation. METHODS: Data were extracted from September 2018 through June 2020 from the Midwest component of EMRClaims+®, an integrated health services database containing > 20 million medical records from national commercial insurance claims, Medicare claims, and regional electronic medical records. Patients included in the cohort analysis were aged ≥ 18 years and were administered fremanezumab, with enrollment or treatment history for ≥ 6 months prior (pre-index) to initiating fremanezumab (index date) and ≥ 1 month after the index date (post-index), and without pregnancy or pregnancy-related encounters during the study period. Patient-reported headache frequency, migraine pain intensity (MPI), composite migraine symptoms, and HCRU were assessed pre-index and ≥ 1 month after fremanezumab initiation. Wilcoxon signed-rank tests were used to compare means of migraine symptoms and outcomes and HCRU before and after fremanezumab initiation. RESULTS: Overall, 172 patients were eligible for analysis. Of patients who self-reported (n = 129), 83.7% reported improvement in headache frequency or symptoms after fremanezumab treatment. Specifically, headache frequency decreased by 63% after fremanezumab initiation: mean (standard deviation) headache frequency was 22.24 (9.29) days per month pre-index versus 8.24 (7.42) days per month post-index (P < 0.0001). Mean MPI also decreased by 18% after fremanezumab initiation: MPI was 5.47 (3.19) pre-index versus 4.51 (3.34) post-index (P = 0.014). Mean emergency room (ER) visits per month decreased from 0.72 to 0.54 (P = 0.003), and mean outpatient visits per month decreased from 1.04 to 0.81 (P < 0.001). Mean hospitalizations per month decreased, but the results did not reach statistical significance (P = 0.095). Hospitalization and ER costs decreased, while outpatient costs increased, from pre-index to post-index, but differences were not statistically significant (P ≥ 0.232). CONCLUSIONS: Significant reductions in headache frequency, MPI, and HCRU were observed after fremanezumab initiation in patients with migraine in a US real-world setting.

Add-on tiotropium versus step-up inhaled corticosteroid plus long-acting beta-2-agonist in real-world patients with asthma.

Background: A step-up approach (increasing inhaled corticosteroid [ICS] dose and/or add-on treatment) is recommended for asthma that is uncontrolled despite ICS plus long-acting beta-2-agonist (LABA) combination treatment. Understanding the impact of different treatment options on health outcomes can help guide treatment decision-making. Objective: To compare the effectiveness of add-on tiotropium 1.25 µg (two puffs once daily) versus an increased ICS plus LABA dose in a real-world cohort of patients with asthma initiated on ICS plus LABA. Methods: De-identified data from patients ages ≥12 years and with asthma who were initiated on ICS plus LABA, and then had tiotropium added (Tio group; index date) or an ICS plus LABA dose increased (inc-ICS group; index date) were collected from two medical and pharmacy claims data bases (2014-2018). To account for population/group differences, propensity score matching was performed. The primary end point was the exacerbation risk after the index date. Secondary end points included exacerbation rates 6 and 12 months postindex, health-care resource utilization, costs, and short-acting beta-2-agonist (SABA) refills 12 months postindex. Results: Overall, 7857 patients (Tio group, 2619; inc-ICS group, 5238) were included. The exacerbation risk was 35% lower in the Tio group than in the inc-ICS group (hazard ratio 0.65 [95% confidence interval, 0.43-0.99]; p = 0.044). Exacerbation rates in the Tio group also were significantly lower within 6 and 12 months postindex (64% and 73%, respectively). All-cause and asthma-related emergency department (ED) visits were 47% and 74% lower, respectively (p < 0.0001 for both), and all-cause and asthma-related hospitalizations were 48% (p < 0.01) and 76% (p < 0.001) lower, respectively, in the Tio group. Also, significantly fewer patients in the Tio group versus the inc-ICS group required SABA refills (56% versus 67%, p < 0.0001). Conclusion: Add-on tiotropium significantly decreased the risk and rate of exacerbations, decreased all-cause and asthma-related ED visits and hospitalizations, and reduced SABA refills compared with increasing the ICS plus LABA dose. The findings supported the use of add-on tiotropium for patients with uncontrolled asthma taking ICS plus LABA.

Effect of clinically significant thresholds of eosinophil elevation on health care resource use in asthma.

BACKGROUND: Blood eosinophil counts correlate with exacerbations, but there is a lack of consensus on a clinically relevant definition of eosinophil count elevation. OBJECTIVE: To analyze health care resource use among patients with elevated blood eosinophil counts defined at 150 cells/µL or greater and 300 cells/µL or greater. METHODS: Data on patients who received a diagnosis of asthma between 2007 and 2016 were extracted from EMRClaims + database. Patients were defined as having elevated eosinophil counts if any test result during 3 months before follow-up found blood eosinophil count of 150 cells/µL or more or 300 cells/µL or more. Hospitalizations, emergency department visits, outpatient visits, and associated costs were compared. With logistic regression, likelihood of hospitalization was assessed in the presence of eosinophil elevation. RESULTS: Among 3687 patients who met the study criteria, 1152 received a test within 3 months before the follow-up period, of whom 644 (56%) had elevated eosinophil counts of 150 cells/µL or greater and 322 (29%) had eosinophil counts of 300 cells/µL or greater. Overall, the mean (SD) number of hospitalizations for patients with elevated eosinophil counts vs the comparator was significantly greater (0.29 [0.92] vs 0.17 [0.57], P < .001 at ≥150 cells/µL and 0.30 [0.95] vs 0.18 [0.61] at ≥300 cells/µL, P = .001). The total mean cost was significantly greater for patients with elevated eosinophil counts (at ≥150 cells/µL: $10,262 vs $7149, P < .001 and at ≥300 cells/µL: $9966 vs $7468, P = .003). CONCLUSION: Patients with asthma incurred greater health care resource use when their blood eosinophil counts were elevated at 150 cells/µL or greater and 300 cells/µL or greater as measured within 3 months of follow-up.

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.

Progression to Uncontrolled Severe Asthma: A Novel Risk Equation.

BACKGROUND: Recently published asthma guidelines by the European Respiratory Society and the American Thoracic Society (ERS-ATS) define severe disease based on medication use and control level. These guidelines also emphasize that asthma severity involves certain biomarker phenotypes, one of them being eosinophilic phenotype. The quantification of the influence of eosinophil level toward predicting disease severity can help decision makers manage therapy better earlier. OBJECTIVE: To develop a risk-scoring algorithm to identify patients at greater risk of developing uncontrolled severe asthma as defined by ERS-ATS guidelines. METHODS: Data on asthma patients were extracted from the EMRClaims + database from January 2004 to July 2011. Patients with continuous enrollment 12 months before and after the date of the first encounter with a diagnosis of asthma (index date) with at least 1 blood eosinophil test result in the 12 months after the index date, but before the development of uncontrolled severe asthma or the study end date, were included. Uncontrolled severe asthma was defined as the first date on which all criteria of the ERS-ATS definition were first satisfied in the 12 months after the index date. Age (≥ 50 years vs. < 50 years), race, and sex were measured at index, and the Charlson Comorbidity Index (CCI) score (> 0 vs. 0) was measured in the pre-index period. Elevated eosinophil level was defined as a test result with ≥ 400 cells/µL. The study cohort was randomly split 50-50 into derivation and validation samples. Cox proportional hazards regression was used to develop the risk score for uncontrolled severe asthma using the derivation cohort with independent variables of eosinophil level, age, sex, race, and CCI. A bootstrapping procedure was used to generate 1,000 samples from the derivation cohort. Variables significant in ≥ 50% of the samples were retained in the final regression model. A risk score was then calculated based on the coefficient estimates of the final model. C-statistic was used to test the model's discrimination power. RESULTS: The study included 2,405 patients, 147 (6%) of whom developed uncontrolled severe asthma. Higher eosinophil level and CCI score > 0 were significantly and independently associated with an increased risk of uncontrolled severe asthma in the derivation cohort (HR = 1.90, 95% CI = 1.17-3.08 and HR = 2.00, 95% CI = 1.28-3.13, respectively); findings were similar in the validation cohort. Total risk score was categorized as 0, 2, and 4. All models showed good C-statistics (0.79-0.80), indicating favorable model discrimination. There was a significantly greater number of patients with uncontrolled severe asthma in the risk score segments of 2 and 4 compared with 0 (each P < 0.0001). CONCLUSIONS: A risk stratification tool using peripheral eosinophil counts and CCI can be used to predict the development of uncontrolled severe asthma. DISCLOSURES: This study was funded by Teva Pharmaceuticals. eMAX Health Systems was a consultant to Teva Pharmaceuticals for this study and received payment from Teva Pharmaceuticals for work on this study. Casciano and Dotiwala are employed by eMAX Health Systems. Krishnan, Li, and Martin received payment from eMAX Health Systems for work on this study. Small was employed by Teva Pharmaceuticals at the time of this study. Study concept and design were contributed primarily by Casciano, Krishnan, Small, and Martin, along with Li and Dotiwala. Dotiwala, Casciano, Small, and Li collected the data, along with Martin and Li and Krishnan. Data interpretation was provided by Martin, Casciano, and Li, with assistance from the other authors. The manuscript was written by Li, Casciano, Dotiwala, and Small, with assistance from the other authors, and revised by Dotiwala, Small, Li, and Martin, with assistance from Krishnan and Casciano.

Burden of asthma with elevated blood eosinophil levels.

BACKGROUND: Asthma is a common chronic condition with an economic burden of almost $56 billion annually in the US. Biologic markers like blood eosinophils, that help predict the risk of exacerbation could help guide more optimal treatment plans and reduce cost. The purpose of this study was to determine whether healthcare resource use and expenditures vary by eosinophil level among patients with asthma. METHODS: Patients with a diagnosis of asthma defined by ICD-9-CM code 493.xx between January 2004 and July 2011 were extracted from EMRClaims + database (eMAX Health, White Plains NY). Patients were classified as mild, moderate, or severe by medication use following diagnosis, based on recommendations of National Institutes of Health Expert Panel Report 3. Patients were classified as those with elevated eosinophils (≥400 cells/µL) and normal eosinophil level (<400 cells/µL). Patients were followed for resource use, defined as hospitalizations, ER visits and outpatient visit and associated costs were calculated to assess whether an economic difference exists between eosinophil groups. Non-parametric tests were used to compare resource use and associated cost between elevated and normal eosinophil groups. Multivariate modeling was performed to assess the contribution of eosinophil level on the likelihood of study outcomes among patients with severe asthma. RESULTS: Among the 2,164 patients meeting eligibility criteria, 1,144 had severity designations. Of these, 179(16 %) of patients had severe asthma of which 20 % (n = 35) had elevated eosinophils. Seventeen percent of patients with elevated eosinophils were admitted to the hospital during the follow-up period, significantly greater than patients with normal eosinophil levels (12 %; p = 0.011). Overall, compared to patients with normal eosinophil levels (n = 1734), patients with elevated eosinophil levels (n = 430) had significantly greater mean annual hospital admissions (0.51 vs. 0.21/year, p = 0.006) and hospital costs (2,536 vs. $1,091, p = 0.011). Logistic regressions showed that elevated eosinophil level was associated with 5.14 times increased odds of all cause admissions (95 % CI:1.76-14.99, p = 0.003) and 4.07 times increased odds of asthma related admissions (95 % CI: 1.26-13.12, p = 0.019). CONCLUSION: Eosinophil elevation was associated with greater healthcare resource use in patients with asthma.

Value of peripheral blood eosinophil markers to predict severity of asthma.

BACKGROUND: Asthma represents a significant clinical and economic burden to the US healthcare system. Along with other clinical manifestations of the disease, elevated sputum and blood eosinophil levels are observed in patients experiencing asthma exacerbations. The aim of this study was to evaluate the association between blood eosinophil levels and asthma severity defined using Expert Panel Report 3 guidelines. METHODS: Patients with asthma diagnosis between 2004 and 2011 were extracted from the EMRClaims+ database (eMAX Health, White Plains, NY) containing electronic medical records linked to insurance claims for over 675,000 patients. The date of first asthma diagnosis was defined as the 'index date'. Patients were required to have at least 1 peripheral eosinophil test (elevated defined as ≥ 400 cells/µL) in the 12 month 'assessment' period following the index date. We classified patients as those with mild asthma and moderate-to-severe asthma based on the pattern of medication use, as recommended by the 2007 National Institutes of Health Expert Panel Report. Logistic regression models were used to determine if patients with moderate-to-severe asthma had increased likelihood of an elevated peripheral eosinophil count, after accounting for demographics and comorbidities. RESULTS: Among 1,144 patients with an asthma diagnosis, 60 % were classified as having moderate-to-severe asthma. Twenty four percent of patients with moderate-to-severe asthma and 19 % of patients with mild asthma had an elevated peripheral eosinophil count (p = 0.053). Logistic regression showed that moderate-to-severe asthma was associated with 38 % increased odds of elevated eosinophil level (OR 1.38, 95 % CI: 1.02 to 1.86, p = 0.04). CONCLUSION: Patients with moderate-severe asthma are significantly more likely to have an elevated peripheral eosinophil count than patients with mild asthma.

Economic burden of recurrent venous thromboembolism: analysis from a U.S. hospital perspective.

PURPOSE: An analysis of resource utilization and hospital costs associated with recurrent venous thromboembolism (VTE) is presented. METHODS: A retrospective cohort analysis was conducted using a large U.S. hospital database. Patients with VTE-related hospitalization events during the period January-December 2010 were identified; data collection extended for up to 12 months after the index event. Postdischarge hospital resource use and total costs were compared in cohorts of patients with and without recurrent VTE. Regression analysis was performed to compare hospital costs and length of stay (LOS) during initial and subsequent VTE encounters. RESULTS: Among the study population of 43,734 patients, 4% had postdischarge VTE-related events during the data collection period. The median and mean ± S.D. times to VTE recurrence were 48 days and 98 ± 106 days, respectively. Patients with recurrent VTE had more all-cause hospitalizations than those without recurrent VTE (mean ± S.D., 1.07 ± 0.96 versus 0.15 ± 0.53; p < 0.0001), more all-cause emergency room visits (mean ± S.D., 0.31 ± 0.66 versus 0.05 ± 0.31; p < 0.0001), and greater total costs (mean ± S.D., $28,353 ± $39,624 versus $17,712 ± $33,461; p < 0.0001). Relative to initial VTE admissions, admissions for recurrent VTE were, on average, associated with a 14% longer LOS (p = 0.0002) and a 22% higher total cost (p < 0.001). CONCLUSION: Patients with recurrent VTE used more hospital resources than those without recurrent VTE. Readmissions for VTE were significantly longer and more costly than index encounters.

The costs of warfarin underuse and nonadherence in patients with atrial fibrillation: a commercial insurer perspective.

BACKGROUND: Atrial fibrillation (AF) imposes a substantial clinical and economic burden on the U.S. health care system. Despite national guidelines that recommend oral anticoagulation for stroke prevention, the literature consistently reports its underuse in AF patients with moderate to high stroke risk. OBJECTIVE: To assess the economic burden of underuse and nonadherence of warfarin therapy among patients with nonvalvular AF in a commercially insured population. METHODS: Claims data between January 2003 and December 2007 from the Thomson Reuters MarketScan Research Database were used. Patients diagnosed with nonvalvular AF who were continuously enrolled for at least 12 months prior to and 2 months following their diagnosis, who had a CHADS2 score ≥ 2, and were not at high risk of bleeding (ATRIA score less than 5, HEMORR2HAGE score less than 4, and HAS-BLED score less than 3) at baseline were included. Patients were followed for up to 18 months after the AF diagnosis date to assess the level of warfarin utilization. Health care resource utilization and cost during follow-up among patients with the proportion of days covered (PDC) by warfarin greater than 0.8 (high) and ≤ 0.8 (low) versus patients with no warfarin exposure were assessed. Multivariate negative binomial regressions and generalized linear models were used to estimate differences in resource utilization and cost, respectively. RESULTS: Of the 13,289 subjects included in this analysis, 47% had no warfarin exposure; 31.5% had low PDC; and 21.5% had high PDC. The rates of ischemic stroke and transient ischemic attack (per 100 patient-years) were significantly lower for the groups that had high and low PDCs as compared with the group with no warfarin exposure (P less than 0.001). Multivariate analysis showed that patients with high PDC were 27% less likely (P less than 0.001) to incur hospitalizations, and 16% were less likely (P = 0.019) to incur emergency room visits than patients who did not receive warfarin, but the differences between low PDC patients and no warfarin exposure were not significant. Although both low and high PDC were associated with lower all-cause inpatient cost (P less than 0.001), only high PDC was associated with a lower post-index all-cause total cost (P less than 0.001) compared with no warfarin exposure. CONCLUSION: Our results confirm that underutilization and nonadherence of warfarin among nonvalvular AF patients is both prevalent and costly. Warfarin use among patients with moderate to high stroke risk and low to moderate bleed risk demonstrated a stroke benefit without a significant increase in intracranial hemorrhage. Adherence to oral anticoagulant therapy was associated with a significant reduction in inpatient service use and total health care cost. Improving adherence to oral anticoagulation is important to attaining the clinical and economic benefits of therapy.

Anticoagulation therapy for patients with non-valvular atrial fibrillation: comparison of decision analytic model recommendations and real-world warfarin prescription use.

BACKGROUND: Anticoagulation in patients with atrial fibrillation (AF) is challenging because stroke-risk reduction must be balanced against increased bleeding risk. OBJECTIVE: We developed a decision model integrating both stroke and bleeding risk schemes to guide optimal use of anticoagulation in AF, and compared model recommendations with warfarin use in a real-world database. METHODS: A Markov model based on demographics, CHADS(2) (Congestive Heart Failure, Hypertension, Age of 75 years and greater, Diabetes Mellitus and History of Stroke) stroke and ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleed risk scores, and anticoagulation treatment effects from clinical trials simulated health state transitions for recently diagnosed AF patients. The model recommended the treatment with greater quality-adjusted life expectancy. Model recommendations were contrasted with actual warfarin use recorded in the Thomson Reuters MarketScan database (N = 64,946). RESULTS: 74.8% (n = 48,548) of the Marketscan AF cohort had CHADS(2) ≥1, of whom 14.3% had moderate/high (≥4) ATRIA bleeding risk. While the model recommended warfarin for almost all patients with CHADS(2) ≥1 who are at low bleeding risk, it recommended warfarin for fewer patients as bleeding risk increased. Of the 44,611 patients recommended warfarin, 63.4% of patients were considered warfarin exposed (concordant with model recommendation), and of the 20,335 patients recommended aspirin (acetylsalicylic acid), 59.7% received warfarin (discordant with model recommendations). Actual warfarin use decreased modestly with higher stroke risk (p < 0.0001) and with higher bleeding risk (p < 0.0001). CONCLUSION: High discordance between actual warfarin use and model recommendations suggests that anticoagulation decisions are not based on systematic evaluation of stroke and bleeding risks. Model-based clinical decision aids may improve oral anticoagulation decisions by more systematically weighing bleed and stroke risk.

Economic analysis of oral and topical therapies for onychomycosis of the toenails and fingernails.

OBJECTIVE: Several antifungal agents are indicated for onychomycosis, a fungal infection of the toenails and fingernails. These agents differ in their dosing regimen, efficacy, adverse events profile, potential for drug interaction, and cost. We conducted a pharmacoeconomic analysis of oral and topical therapies for onychomycosis from the perspective of a hypothetical managed care payer to determine the most cost-effective agent. DESIGN: A decision analytic model was developed to evaluate the pharmacoeconomic profiles of itraconazole-continuous (Sporanox, Janssen Pharmaceutica), itraconazole-pulse (Sporanox, Janssen Pharmaceutica), terbinafine (Lamisil, Novartis Pharmaceuticals), and ciclopirox (Penlac, Dermik Laboratories) in the treatment of fingernail and toenail onychomycosis. METHODOLOGY: We conducted a meta-analysis of the available literature to populate the decision analytic model with clinical point estimates for success, failure, and relapse. A panel of expert dermatologists defined resources consumed during the onychomycosis treatment process. These resources were then assigned values, using publicly available data sources, to reflect the U.S. managed care perspective. These clinical and economic data elements were integrated in the decision analytic model to arrive at the expected cost of treatment for each drug. Additionally, incremental cost-effectiveness was calculated for treatment success and disease-free days achieved by each therapy. Finally, a policy-level analysis of the budgetary impact of using the therapies for onychomycosis in a managed care setting was conducted. RESULTS: The meta-analysis demonstrated terbinafine to be the therapeutic alternative with the highest success rate for both fingernails (96.55 percent) and toenails (81.15 percent). Terbinafine also had the lowest relapse rate (6.42 percent) and the highest number of disease-free days for both fingernails and toenails. Subsequently, in terms of cost-effectiveness, terbinafine dominated all other comparators for fingernails and toenails. CONCLUSIONS: Based on the patient-level analysis, we concluded that terbinafine is the most cost-effective therapy in the treatment of onychomycosis from a managed care perspective. Furthermore, at the policy level, increased utilization of terbinafine among onychomycosis patients is likely to reduce the managed care organizations' per member per month cost.

Impact of rivastigmine on costs and on time spent in caregiving for families of patients with Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) places a significant burden on health care systems worldwide. As new treatments are developed, their cost-effectiveness is often assessed to help health care professionals make informed decisions. In addition to the more common practice of assessing direct medical costs, indirect costs, including time spent in caregiving, should be evaluated. METHODS: This study examined the potential effects of the dual cholinesterase inhibitor rivastigmine (Exelon) on caregivers of patients with AD. Results from two 26-week, placebo-controlled trials have demonstrated the clinically relevant and statistically significant efficacy of rivastigmine (6-12 mg/day) compared to placebo, on cognition, activities of daily living, and global functioning. By delaying progression of AD, significant savings in caregiver burden are anticipated, as measured by time spent caregiving and its related costs. Data collected in a prospective, observational study of AD patients and their caregivers were used to establish the relationship between disease severity (based on Mini-Mental State Examination [MMSE] score) and time spent caregiving (according to the 5-item Caregivers Activity Survey score). A significant correlation was observed between the two scores (N = 43, r = -.56, p < .0001), demonstrating that more time for supervision from caregivers is required as the disease progresses. This finding was used to estimate the reduced caregiver burden resulting from the delay in disease progression that was demonstrated with use of rivastigmine. RESULTS: Over a 2-year period, the reduction in time spent in caregiving reached 691 hours for caregivers of patients with mild AD (MMSE score 21-30), resulting in a total savings of approximately 11,253 dollars. Treatment of patients with moderately severe AD was also evaluated. The trend was similar but the impact was less, suggesting an economic benefit to early therapy. CONCLUSION: Early diagnosis and a pharmacologic intervention that allows the patients to remain at home longer by delaying disease progression would have a beneficial impact on patients, caregivers, and payers, and should therefore be encouraged through initiatives designed to identify and treat patients early in the course of disease.

Cardiovascular disease costs associated with uncontrolled hypertension.

This research evaluated the effect of inadequate blood pressure (BP) control on selected cardiovascular (CV) disease outcomes and costs for American patients with hypertension. The results of a hypertension outcomes trial, which provided incidence rates for CV disease morbidity and mortality at distinct systolic/diastolic BP ranges, were integrated with U.S. hypertension statistics from the Third National Health and Nutrition Examination Survey and cost estimates for stroke, congestive heart failure, and myocardial infarction. A model was developed to estimate the number of cases and costs of myocardial infarction, stroke, and congestive heart failure for patients achieving BP control versus those not achieving control. For the U.S. population with hypertension, inadequate BP control was estimated to result in 39,702 CV events, 8,374 CV disease deaths, and $964 million in direct medical expenditures. Within the medicated population with CV disease, the incremental costs of failure to attain BP goals reached approximately $467 million. These results reflect the importance of adequate BP control--in particular, systolic BP control--in reducing cardiovascular morbidity, mortality, and overall health care expenditures among patients with hypertension.

Best practice treatment algorithm for primary open-angle glaucoma: implications for U.S. ophthalmology practice.

The objective of this study was to develop a "best-practice" treatment algorithm for the management of primary open-angle glaucoma in patients receiving initial medical therapy, to serve as a consideration for future ophthalmology practice. For comparison, a baseline, "common-practice" treatment algorithm was also created that reflects current ophthalmology practice patterns. Survey instruments were developed based on a comprehensive review of relevant literature, along with input from a general ophthalmologist. A panel of eight ophthalmologists subspecialized in glaucoma management was surveyed. Consensus was achieved using a modified Delphi technique. A comparison of common- and best-practice treatment algorithms suggests that in contrast with expert opinion, nonselective beta blockers are currently used more often, and alpha-2 agonists less often, as first-line therapy for the treatment of primary open-angle glaucoma.

Economic benefits of amlodipine treatment in patients with coronary artery disease.

OBJECTIVE: To estimate the potential savings in overall cardiovascular disease (CVD) treatment costs for the US population with coronary artery disease (CAD) resulting from the use of amlodipine. STUDY DESIGN AND METHODS: Using patient-level data from a retrospective analysis of the Prospective Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), a randomised, placebo-controlled clinical trial (n = 825), we constructed a Markov cohort simulation model to estimate the health economic outcomes of patients with CAD treated with either amlodipine or placebo. PERSPECTIVE: Healthcare payer perspective. RESULTS: The expected number of CVD events for amlodipine recipients was significantly lower than the number of CVD events in the placebo cohort (p < 0.01). The net present value of the cost per patient for CVD treatment was estimated to be $US14 117 for amlodipine recipients and $US16 683 (1999 values, assuming a 3% discount rate) for placebo recipients over 3 years of follow-up with cost savings realised in the amlodipine cohorts after 6 months. CONCLUSIONS: According to the model, amlodipine results in an expected per patient cost savings of $US2566 over a 3-year period, mainly due to a reduction in hospitalisations for cardiovascular-related events and procedures.

A pharmacoeconomic evaluation of results from the Coronary Angioplasty Amlodipine Restenosis Study (CAPARES) in Norway and Canada.

INTRODUCTION: The objective of this analysis was to evaluate the health economic benefits of using amlodipine in patients undergoing angioplasty procedures in Canada and Norway. METHODS: A decision tree model was constructed to find the total expected cost per patient for a 4-month time period following an initial angioplasty. The model used clinical data from the Coronary Angioplasty Amlodipine Restenosis Study (CAPARES), a prospective, randomized, double blind, placebo-controlled trial conducted to investigate the effects of amlodipine on restenosis and clinical events in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Outcomes of interest to this analysis included MI, repeat PTCA, CABG, and all-cause mortality. Clinical experts from Canada and Norway were enlisted and a modified Delphi study approach was used to quantify healthcare resources consumed for each clinical outcome. RESULTS: The use of amlodipine decreased the rates of MI, PTCA, and CABG by 2.0, 4.7, and 2.7%, respectively. The total expected cost per patient using amlodipine was $6,398.30 (US$4,323) in Canada and kr 59,993.27 (US$6,846) in Norway. The total expected cost per patient not using amlodipine was $6,519.37 (US$4,405) in Canada and kr 64,292.17 (US$7,337) in Norway. The model demonstrated potential cost-savings over a 4-month follow up period resulting from the improved clinical outcomes for patients using amlodipine with PTCA--$121,071 (US$81,844) per 1000 patients in Canada and kr 4,298,899 (US$490,074) per 1000 patients in Norway. CONCLUSIONS: The adjunctive use of amlodipine is a cost-effective therapeutic strategy to achieve more favorable clinical outcomes in patients undergoing PTCAs in Canada and Norway.