Disease-Modifying Therapy Adherence and Associated Factors in a National Sample of Medicare Patients With Multiple Sclerosis.

OBJECTIVES: Disease-modifying therapies (DMTs) reduce relapse rates and disability progression for relapsing multiple sclerosis (MS). Although 25% to 30% of all US patients with MS are Medicare beneficiaries, limited information exists on this population. This is the first study using national Medicare data to (1) describe characteristics of patients with MS using DMTs, (2) estimate adherence to DMTs over a 1-year and 3-year follow-up, and (3) examine factors associated with DMT adherence. METHODS: This retrospective claims analysis used 2011-2014 100% Medicare files. Monthly adherence to MS DMTs was defined as the proportion of days covered ≥0.80 with any DMT in each month for 1-year (n = 36 593) and 3-year (n = 17 599) follow-up samples of MS DMT users. Generalized estimating equation logistic regressions were used to estimate factors associated with adherence to DMTs. RESULTS: Over 90% of patients were eligible for Medicare owing to disability, and about three-quarters qualified for low-income subsidies. A downward trend in DMT adherence was observed over time in both samples. Monthly adherence dropped significantly between December of the prior year to January of the following year (from 76% to 65% in the 1-year follow-up sample and similar drops seen across all years in the 3-year follow-up sample). Multivariable regressions indicated characteristics such as being low-income, having a disability, and having high patient out-of-pocket DMT costs associated with poor adherence to DMTs. CONCLUSION: Our study provides important insights into the characteristics and DMT adherence of Medicare patients with MS and highlights the need for interventions and policies mitigating barriers to adherence in this population.

Estimation of potential cost savings associated with reduced rates of cardiovascular hospitalization among atrial fibrillation/flutter patients treated with dronedarone in the ATHENA trial.

The aim of this study was to estimate, from a US payer perspective, potential cost savings resulting from the reduction in cardiovascular (CV) hospitalizations obtained with dronedarone in the ATHENA (A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg bid for the Prevention of Cardiovascular Hospitalization or Death from any Cause in PatiENts with Atrial Fibrillation/Atrial Flutter) trial. ATHENA randomized atrial fibrillation/flutter patients to dronedarone (n=2301) or placebo (n=2327) plus standard care. Dronedarone significantly reduced first CV hospitalization/all-cause mortality over 12-30 months of follow-up. CV hospitalization costs (2008 values) from a US cohort of ATHENA-like atrial fibrillation/flutter patients with Medicare supplemental insurance (n=10,200) and diagnosis-related group costs of adverse event-related hospitalizations were applied to hospitalizations occurring in ATHENA. The impact of cost variation was assessed using Monte Carlo simulation. In ATHENA, dronedarone reduced the overall CV hospitalization rate (vs. placebo) by 29% over the first 12 months (33.36 vs. 47.19 events per 100 patients) and by 25% over the full study (51.15 vs. 68.55 events per 100 patients). Adverse event-related hospitalization rates (dronedarone vs. placebo) were low (0.48 vs. 0.21 and 0.56 vs. 0.26 events per 100 patients over 12 months and the full study, respectively). Overall hospitalization cost savings were estimated at $1329 and $1763 per patient over 12 months and the full study, respectively. Cost savings were relatively stable [mean (95% confidence interval): $1330 ($994-$1676) for the first 12 months and $1763 ($1369-$2184) for the full study] over 10,000 cycles of random variation.

Burden, timing, and relationship of cardiovascular hospitalization to mortality among Medicare beneficiaries with newly diagnosed atrial fibrillation.

BACKGROUND: Limited data exist on the burden and relationship of cardiovascular (CV) hospitalization to mortality after newly diagnosed with atrial fibrillation (AF). METHODS: Using a 20% sample of nationwide Medicare Part A and B claims data, we performed a retrospective cohort study of Medicare beneficiaries with newly diagnosed AF (2004-2008). Cox proportional hazards time-varying exposures were used to determine the risk of death among patients with CV hospitalization after AF diagnosis. RESULTS: Of 228,295 patients (mean age 79.6 ± 7.4 years, 56% female), 57% had a CV hospitalization after diagnosis of AF (41% in the first year). The most common primary CV hospitalization diagnoses were AF/supraventricular arrhythmias (21%), heart failure (19%), myocardial infarction (11%), and stroke/transient ischemic attack (7.7%). Incidence rates per 1,000 person-years among patients with and without CV hospitalization were 114 and 87, respectively, for all-cause mortality. After adjustment for covariates and time to CV hospitalization, the hazard of mortality among newly diagnosed AF patients with CV hospitalization, compared with those without CV hospitalization, was higher (hazard ratio 1.22, 95% CI 1.20-1.24). CONCLUSIONS: Cardiovascular hospitalization is common in the first year after AF diagnosis. Atrial fibrillation, heart failure, myocardial infarction, and stroke/transient ischemic attack account for half of primary hospitalization diagnosis. Cardiovascular hospitalization is independently associated with mortality, irrespective of time from diagnosis to first hospitalization, and represents a critical inflection point in survival trajectory. These findings highlight the importance of CV hospitalization as a marker of disease progression and poor outcomes. Efforts to clarify the determinants of hospitalization could inform interventions to reduce admissions and improve survival.

Cost-effectiveness of dronedarone and standard of care compared with standard of care alone: US results of an ATHENA lifetime model.

BACKGROUND: The first antiarrhythmic drug to demonstrate a reduced rate of cardiovascular hospitalization in atrial fibrillation/flutter (AF/AFL) patients was dronedarone in a placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter (ATHENA trial). The potential cost-effectiveness of dronedarone in this patient population has not been reported in a US context. This study assesses the cost-effectiveness of dronedarone from a US health care payers' perspective. METHODS AND RESULTS: ATHENA patient data were applied to a patient-level health state transition model. Probabilities of health state transitions were derived from ATHENA and published data. Associated costs used in the model (2010 values) were obtained from published sources when trial data were not available. The base-case model assumed that patients were treated with dronedarone for the duration of ATHENA (mean 21 months) and were followed over a lifetime. Cost-effectiveness, from the payers' perspective, was determined using a Monte Carlo microsimulation (1 million fictitious patients). Dronedarone plus standard care provided 0.13 life years gained (LYG), and 0.11 quality-adjusted life years (QALYs), over standard care alone; cost/QALY was $19,520 and cost/LYG was $16,930. Compared to lower risk patients, patients at higher risk of stroke (Congestive heart failure, history of Hypertension, Age ≥ 75 years, Diabetes mellitus, and past history of Stroke or transient ischemic attack (CHADS(2)) scores 3-6 versus 0) had a lower cost/QALY ($9580-$16,000 versus $26,450). Cost/QALY was highest in scenarios assuming lifetime dronedarone therapy, no cardiovascular mortality benefit, no cost associated with AF/AFL recurrence on standard care, and when discounting of 5% was compared with 0%. CONCLUSIONS: By extrapolating the results of a large, multicenter, randomized clinical trial (ATHENA), this model suggests that dronedarone is a cost-effective treatment option for approved indications (paroxysmal/persistent AF/AFL) in the US.

Outcomes in atrial fibrillation patients on combined warfarin & antiarrhythmic therapy.

BACKGROUND: This retrospective cohort study compared rates of treatment persistence, incidences of de novo stroke, arterial embolism, and hemorrhage/bleeding, and healthcare resource use and costs between atrial fibrillation/flutter (AF/AFL) patients receiving concomitant warfarin (W)+amiodarone (A) or warfarin+other antiarrhythmic drug (OAAD) therapy in real-world practice. METHODS: The Ingenix IMPACT database (1997-2009) was used to identify patients with ≥ 1 diagnostic claim for AF/AFL and concurrent pharmacy claims (≥ 60 days' supply) for W and A (n=4238) or W+OAAD (n=6332) within the first 90 days of initiating therapy. Outcomes of interest were assessed over 12 months following initiation of dual therapy. RESULTS: The W+A cohort was older than the W+OAAD cohort (mean 66.5 vs. 61.9 years) and had greater baseline comorbidity. The W+A cohort had significantly 1) lower rates of treatment persistence; 2) higher incidences of de novo stroke (hazard ratio [HR] 1.24), arterial embolism (HR 1.48) and combined stroke/hemorrhage/bleeding/arterial embolism (HR 1.25); 3) more frequent inpatient (incidence rate ratio [IRR] 1.25), emergency room (IRR 1.16) and outpatient (IRR 1.07) admissions; and 4) higher incidences of cardiovascular- (IRR 1.35) and arterial embolism- (IRR 1.94) related healthcare use than the W+OAAD cohort. Incremental total healthcare costs over 12 months were $4114 ($2397 inpatient; $1171 outpatient). CONCLUSIONS: Allowing for differences in prescribing practice, AF/AFL patients treated with W+A are at higher risk of stroke and arterial embolism, and have higher healthcare use and costs, than patients receiving W+OAAD.

Hospital readmissions in US atrial fibrillation patients: occurrence and costs.

The aim of the study was to examine the temporal readmission pattern, proportion of readmissions attributed to cardiovascular (CV) causes, and the duration and costs associated with readmission in hospitalized patients with atrial fibrillation/flutter (AF/AFL). This retrospective cohort study used medical claims data from the PharMetrics Patient-Centric database (IMS Health, Watertown, MA) between January 2007 and March 2008. The patients hospitalized with a primary diagnosis of AF/AFL and with ≥12 months' continuous medical and prescription coverage before and after the initial AF/AFL hospitalization were identified from this database. The main outcome measures were rehospitalization patterns [all-cause, all CV-related (including AF/AFL), and AF/AFL-related only], which were assessed over the 12-month post-index period, and costs of initial and subsequent AF/AFL-related hospitalizations that were compared. The study included 8035 patients with AF/AFL (mean age 66.1 years; 57.6% males). Rehospitalization was common (37.9% of patients), with the most frequent causes being CV (34.1%) and, specifically, AF/AFL-related (26.8%). The highest proportion of rehospitalizations occurred within 30 days of the initial hospitalization (25%). Readmissions with a primary diagnosis of AF/AFL (n = 1238) were significantly longer (4.0 vs. 3.6 days; P = 0.0229) and more costly (US$8966 vs. US$7080; P < 0.0001) than the index hospitalization. Hospitalized AF/AFL patients experience high rates of CV- and AF/AFL-related readmissions, particularly within the first 30 days. Subsequent AF/AFL-related readmissions incur higher costs than the initial AF/AFL hospitalization. Treatments resulting in reduced readmissions would improve patient outcomes, quality of life and the cost burden associated with AF/AFL.

Healthcare cost attributable to recently-diagnosed breast cancer in a privately-insured population in the United States.

OBJECTIVE: To evaluate breast cancer-associated healthcare cost from the payer perspective for the initial year after diagnoses of invasive breast cancer. BACKGROUND: Breast cancer is the second most common malignancy in American women. While lifetime burden-of-care studies have reported spending between $20,000 and $100,000 per patient, previous studies have not outlined first year cost in managing this disease in recently diagnosed patients. METHODS: This study was a retrospective, matched cohort study of privately-insured patients. Data were from a large US employers' health claims database (January 2003-September 2008). Breast cancer cases were identified by ICD-9-CM diagnostic codes on index and confirmatory claims. A control group was identified with a ratio of 3:1, matched by demographic and health plan characteristics. Comorbidities were analyzed using the Charlson comorbidity index and AHRQ Comorbidity Software. A multivariate, log-linked, generalized linear model evaluated cost contributions of breast cancer in relation to demographic factors, comorbidities, and plan type. RESULTS: The study included 35,057 cases and 105,171 matched controls (mean age 52 years). Common comorbidities included hypertension, diabetes, hypothyroidism, chronic pulmonary disease, and deficiency anemia. In the generalized linear model, the adjusted difference in total healthcare cost was $42,401 per patient within a year, with outpatient services responsible for most of this sum. Breast cancer-associated incremental annual costs per patient in inpatient, outpatient, and prescription categories were $5100, $37,231, and $1037, respectively. LIMITATIONS: These results may not be representative of the entire US, as data were derived from breast cancer patients with private, employer-based health insurance, and lacked covariates including race/ethnicity, education, income, and disease stage. CONCLUSIONS: Recently diagnosed breast cancer represents a substantial economic burden for US healthcare payers.

Temporal pattern and costs of rehospitalization in atrial fibrillation/atrial flutter patients with one or more additional risk factors.

OBJECTIVES: The ATHENA study showed that use of dronedarone reduced rates of first cardiovascular (CV) hospitalization in atrial fibrillation/flutter (AF/AFL) patients. AF is associated with high costs to payers, which are driven by high rates of hospitalization. This retrospective cohort study examined readmission patterns and costs to US payers in real-world AF/AFL patients with ≥1 additional risk factor (ARF). METHODS: Patients hospitalized (January 2005-March 2008) with AF/AFL as primary diagnosis and having ≥1 year of health coverage, before and after their first (index) admission, were identified in the PharMetrics Patient-Centric database. As in the ATHENA study, patients had to be ≥75 years of age or ≥70 years, with ≥1 ARF. Rehospitalization patterns (all-cause, all CV-related [including AF/AFL] and AF/AFL-related alone) were examined over 1 year post-index, and costs of index vs later AF/AFL admissions compared. RESULTS: The study included 3498 patients (mean 80 [SD 7.6] years; 42.4% men). Over 1 year, 1389 patients (39.7%) were rehospitalized for any cause (mean 1.7 [SD 1.3] events/patient), with 1223 patients (35.0%) undergoing CV-related (mean 1.6 [SD 1.0] events/patient) and 935 (26.7%) undergoing AF-related rehospitalization (mean 1.4 [SD 0.8] events/patient). Common causes of CV-related readmissions (primary diagnosis) were AF/AFL (47.5%), congestive heart failure (CHF) (9.9%), coronary artery disease (7.4%), and stroke/transient ischemic attack (6.2%). Readmission rates at 3 months were 16.2% (all-cause), 14.3% (all CV-related including AF/AFL), and 10.5% (AF/AFL-related alone). AF/AFL readmissions (primary diagnosis) were longer than initial hospitalizations (mean total 6.9 [SD 12.9] vs 4.3 [SD 5.1] days, p < 0.0001) and more costly (median $1819 [25th percentile $1066, 75th percentile $5623] vs $1707 [25th percentile $1102, 75th percentile $4749]). LIMITATIONS: This study excluded patients with pre-existing CHF, did not require electrocardiogram confirmation of AF/AFL diagnosis, and did not distinguish between paroxysmal, persistent, and permanent AF. CONCLUSIONS: AF/AFL patients with ≥1 ARF have high readmission rates. AF/AFL-related readmissions incur higher costs than the initial AF/AFL admissions.

Incremental cost burden to US healthcare payers of atrial fibrillation/atrial flutter patients with additional risk factors.

INTRODUCTION: Atrial fibrillation (AF) and atrial flutter (AFL) patients often have cardiovascular (CV) comorbidities, and have an increased risk of hospitalization and death. Little is known about the real-world cost burden of AF/AFL patients with additional risk factors (ARF). We evaluated the medical resource use and cost burden of AF/AFL patients with ≥1 ARF (other than heart failure [HF]), in comparison with non-AF/AFL controls. METHODS: This retrospective cohort study included patients from the MarketScan Medicare database who had ≥1 inpatient or ≥2 outpatient AF/AFL claims. Patients were (1) ≥75 years of age or (2) 70-74 years of age with ≥1 ARF (hypertension, diabetes, systemic embolism, or stroke/transient ischemic attack), but without HF. The AF/AFL patients were matched on age, gender, region, and enrollment status with non-AF/AFL patients. Hospital resource use and costs over the 12-month post-index period were compared across cohorts. The impacts of comorbidity were seen by subcategorizing hospitalization as all-cause, CV-related, and AF/AFL-related. RESULTS: AF/AFL patients with ≥1 ARF had a higher prevalence of comorbidity than non-AF/AFL patients (n=58,555/cohort). Hospitalizations (all-causality) were more than three times more frequent and of longer duration in AF/AFL patients with ≥1 ARF than in non-AF/AFL controls (mean [SD]: 0.72 [0.87] vs. 0.21 [0.51] hospitalizations per patient per year and 3.85 [9.30] and 1.03 [4.53] days, respectively; both P<0.0001). Overall mean (SD) costs over the 12-month post-index period were higher in AF/AFL patients with ≥1 ARF versus the non-AF/AFL control patients for inpatient ($9613 [25,407] vs. $2625 [11,597]; P<0.0001; incremental cost $6988), outpatient ($9447 [15,062] vs. $4906 [11,715]; P<0.0001; incremental cost $4541), and prescription drug costs ($3430 [3637] vs. $2618 [3374]; P<0.0001; incremental cost $812). CONCLUSION: AF/AFL patients with ≥1 ARF had significantly greater levels of comorbidity, hospitalizations, prescription, and outpatient claims than non-AF/AFL patients. The incremental costs of AF/AFL patients with ≥1 ARF are largely due to higher CV-related inpatient costs.

All-cause health care utilization and costs associated with newly diagnosed multiple sclerosis in the United States.

BACKGROUND: Multiple sclerosis (MS) is a costly and crippling neurologic disease. Approximately 250,000 to 400,000 persons in the United States are currently diagnosed with MS. Most individuals experience their first symptoms between the ages of 20 and 40 years; therefore, this disease may have substantial impact over many years of life on health, quality of life, productivity, and employment. Whereas a number of studies have utilized a cross-sectional design to evaluate the costs associated with MS, no study has used a large administrative claims database to analyze the direct costs associated with newly diagnosed MS. OBJECTIVE: To estimate the additional health care utilization and costs in otherwise healthy patients with newly diagnosed MS. METHODS: This was a retrospective cohort analysis of the Medstat MarketScan Commercial Claims and Encounters database, which is composed of medical and pharmacy claims for approximately 8 million beneficiaries from 45 U.S. commercial health plans. Cases extracted from the database included adults aged 18 to 64 years with either (a) at least 2 medical claims with a diagnosis of MS (ICD-9-CM code 340) in any diagnosis field on the claim or (b) 1 prescription (medical or pharmacy) claim for injectable MS drug therapy (interferon beta-1a, interferon beta- 1b, glatiramer acetate) for dates of service between January 1, 2004, and December 31, 2006. Natalizumab was not used to identify MS cases, but was used to exclude potential comparison group subjects. The index date for patients with MS was the first qualifying diagnosis or pharmacy claim. Each MS patient was matched to 5 "healthy comparison" cases without MS diagnoses or treatment using the following variables: region, insurance type, gender, relation to employee, age, and enrollment period. Cases with any condition listed in the Charlson Comorbidity Index were excluded from both the MS and "healthy comparison" cohorts. Each "healthy comparison" case was assigned the index date of the matching MS patient. Continuous enrollment 12 months pre- and post-index was required for both the MS and "healthy comparison" groups. Costs broken down by type of utilization were adjusted to 2010 dollars using the appropriate medical component of the Consumer Price Index. Use of services and costs were compared using chi-square, t-tests, parametric and nonparametric tests. RESULTS: 1,411 MS cases (65.6% female) were matched to 7,055 "healthy comparison" cases (65.6% female). In the analyses of all-cause health care services during the 12-month post-index period, MS patients were significantly more likely to use all categories of health services examined. Compared with the "healthy comparison" group, new MS patients were 3.5 times as likely to be hospitalized (15.2% vs. 4.3% for MS vs. comparison, respectively), twice as likely to have at least 1 emergency room (ER) visit (25.5% vs. 12.2%) and 2.4 times as likely to have at least 1 visit for physical, occupational, or speech therapy (23.7% vs. 9.9%; P < 0.001 for all comparisons). MS patients also had higher mean 12-month costs related to each category of service (inpatient services $4,110 vs. $836; radiology services $1,693 vs. $259; ER $432 vs. $189; office visits $849 vs. $310; therapies $295 vs. $81, respectively; all P values < 0.001). Total mean 12-month all-cause health care costs were significantly higher for MS patients than for the "healthy comparison" group ($18,829 vs. $4,038, respectively, P < 0.001). Claims attributed to MS by diagnosis code in any field on the claim or use of an MS injectable drug accounted for a mean cost of $8,839 (46.9%), and MS injectable drugs accounted for $4,573 (24.3%) of total all-cause health care costs. CONCLUSIONS: Newly diagnosed MS patients have significantly higher rates of hospitalizations, radiology services, and ER and outpatient visits compared with non-MS "healthy comparison" patients. MS presents a considerable burden to the U.S. health care system within the first year of diagnosis.

Incident surveillance in New Jersey career and technical education programs, 1999 to 2008: attributes, severity, and reported use of personal protective equipment.

Through school-sponsored career and technical education programs in New Jersey, students work part-time during or after school in paid and unpaid structured learning experiences regulated by the New Jersey Department of Education. Schools submit information on "reportable incidents," injury or illness resulting in physician treatment. Incidents including reported use of personal protective equipment (PPE) were assessed; 1,600 incident reports (1999 to 2008) were received. Attributes such as type and severity, body parts affected, and PPE use for incidents occurring at school among students grades 9 to 12 or labeled as "adults" during school hours (n = 285) were analyzed. Older teens incurred more injuries. PPE use was consistently low across age and gender. Students most frequently experienced knife injuries involving fingers and hands. Results identified potential injury determinants and training and intervention topics such as PPE, and support development of an enhanced reporting form.

Cost and resource utilization comparisons of second-generation antihistamines vs. montelukast for allergic rhinitis treatment.

This study evaluates the costs and utilization burden associated with oral, branded second-generation antihistamines (BSGAs) compared with montelukast (MTLK) as first-choice treatment in newly diagnosed allergic rhinitis (AR) patients without asthma. We compared annual medical costs of illness and utilization changes from 1 year before index AR diagnosis to 1 year after for continuously enrolled AR patients initiating therapy with BSGA or MTLK. Multivariate regressions for each outcome variable adjusted for confounders including age, sex, geographic region, Charlson Comorbidity Index, RxRisk Score, 18 comorbidity groups, and payer type. Treatment selection bias was evaluated by propensity score with all covariates plus instrumental variables including physician type and likelihood of prescribing MTLK versus BSGA. Insurance claims data for the years 2003-2007 included AR patients in all regions of the United States. The final sample included 13,703 AR patients taking BSGAs (84%) or MTLK (16%). After confounder adjustment, MTLK patients experienced higher total medical costs ($1,542 versus $989), drug costs ($714 versus $477), AR drug costs ($474 versus $298), and outpatient visit costs ($480 versus $277) than BSGA patients (all values of p < 0.025). MTLK patients experienced higher total visits (0.96), AR outpatient visits (0.71), and comorbidity visits (0.12) than BSGA patients (all values of p < 0.01). MTLK patients were more likely to add additional AR therapy medications (MTLK, 43.2%; BSGA, 31.6%; p < 0.01). New AR patients prescribed MTLK as first-line medication therapy have higher medical costs and resource utilization than those prescribed first-line oral BSGAs. These differences persisted after adjustment for patient fixed effects, available confounders, and treatment propensity scores.

Cost-effectiveness of second-generation antihistamines and montelukast in relieving allergic rhinitis nasal symptoms.

OBJECTIVE: Allergic rhinitis imposes a significant health and economic burden both on individuals and the healthcare system. Second-generation prescription antihistamines, levocetirizine, fexofenadine, and desloratadine, and the leukotriene receptor antagonist, montelukast, differ in their ability to relieve common rhinitis symptoms. The purpose of this study was to compare the cost-effectiveness of prescription agents based on their effectiveness in relieving nasal symptoms. METHODS: Effectiveness was measured as the composite of nasal symptoms, including congestion, rhinorrhea, and sneezing, from clinical studies that compared each of the 4 comparators to placebo. Direct costs included prescription therapy and rhinitis-related physician office visits. Physician office visit costs were collected from an analysis of the PharMetrics insurance claims database. Sensitivity analyses were conducted using a Monte Carlo simulation to assess the robustness of the average and incremental cost-effectiveness ratios. RESULTS: The cost per clinically significant improvement of nasal symptoms for levocetirizine was less than for the other model comparator agents. The incremental cost-effectiveness ratio for levocetirizine dominated montelukast and desloratadine and was lower than either branded or generic fexofenadine. CONCLUSION: Levocetirizine is a cost-effective therapy for the relief of nasal symptoms of allergic rhinitis.