Patient and physician preferences for multiple sclerosis treatments in Germany: A discrete-choice experiment study.

OBJECTIVE: To assess heterogeneity in patient and physician preferences for multiple sclerosis treatment features and outcomes via a discrete-choice experiment. METHOD: Patients with self-reported multiple sclerosis and treating physicians participated in an online discrete-choice experiment. Patients, each considering a better or worse reference condition, and physicians, each considering two patient profiles, chose between hypothetical treatment profiles defined by seven attributes with varying levels: years until disability progression, number of relapses in the decade, mode of administration, dosing frequency, and risks of mild, moderate, and severe side effects. Latent class analysis was used to measure respondent preferences and identify potential subgroups with distinct preferences. RESULTS: Distinct treatment preferences emerged among subgroups of patients (n = 301) and physicians (n = 308). Patients in class 1 (43% of sample) were most concerned about side effects; chief concerns of class 2 patients (57%) were delaying disability progression and avoiding severe side-effect risks. The most important attributes for physicians (by class) were delaying disability (class 1, 45%), avoiding severe side-effect risks and (class 2, 33%), and avoiding all side-effect risks (class 3, 22%). CONCLUSION: Patients and physicians have diverse preferences for multiple sclerosis treatments, reflecting heterogeneity in the disease course and available therapies and the need for shared decision making.

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.

Comparative effectiveness of dimethyl fumarate versus fingolimod and teriflunomide among MS patients switching from first-generation platform therapies in the US.

BACKGROUND: Previous real-world comparative research of MS disease modifying therapies (DMTs) in the overall population has suggested dimethyl fumarate (DMF) to be comparable to fingolimod (FTY) and more efficacious than teriflunomide (TERI) in reducing relapses. However, there is limited comparative evidence in patients switching from platform DMTs in the US. The objective of the study was to compare the annualized relapse rate (ARR) and risk of relapse in MS patients who have switched from a platform therapy to DMF, FTY, or TERI. METHODS: MS patients (18-65 years old) initiating an oral DMT from June 2013 to March 2015 were identified from the Truven MarketScan® Commercial Claims Database. The index date was the date of first oral DMT fill. Patients were required to have: continuous enrollment in the database for 12 months pre-index date and ≥3 months post-index date; ≥1 MS diagnosis over the pre-index period; discontinuation of a platform DMT with no evidence of oral or infusion DMTs over the pre-index period; and adherence to the index drug for ≥90 days. DMF patients were propensity-score matched (PSM) 3:1 to FTY and to TERI based on age, gender, region, a claims-based MS severity measure, ARR, and number of hospitalizations over the pre-index period. Patients were censored when they dropped out of the database or at the end of the study period (March 31, 2016). Post-index relapses were annualized. RESULTS: The database included 20,311 oral DMT users. After applying the study criteria, the PSM yielded 1602:534 switch patients for the DMF-FTY matched cohort. DMF-FTY patients were well-matched on all covariates: age (mean = 44 for both), gender (28% vs. 26% male, respectively), MS severity measure (0.99 vs. 1.08), and baseline ARR (0.40 vs. 0.44). PSM yielded 833:279 switch patients for the DMF-TERI match. DMF-TERI patients were well-matched on all covariates: age (mean = 50), gender (24% vs. 25% male), MS severity measure (0.86 vs. 0.99), and baseline ARR (0.23 vs. 0.30). The standardized differences confirmed balance across all covariates for matched cohorts. The matched DMF-FTY cohorts had comparable post-index ARR (Rate Ratio [RR] = 1.07 [95% Cl: 0.861, 1.328]) and risk of relapse (Hazard Ratio [HR ]= 0.996 [95% CI: 0.803, 1.236]). Post-index ARR was significantly lower with DMF in comparison to TERI (RR = 0.667 [0.486, 0.914]). The risk of relapse was also significantly lower when switching to DMF than TERI (HR = 0.679 [0.503, 0.917]). CONCLUSION: In this analysis, the effectiveness profiles for those oral DMT users specifically switching from platform therapies are consistent with findings from previous research conducted among all oral DMT users, regardless of prior therapy.

Treatment satisfaction significantly improves in patients with multiple sclerosis switching from interferon beta therapy to peginterferon beta-1a every 2 weeks.

OBJECTIVES: Posthoc analysis of treatment satisfaction in patients switching to subcutaneous (SC) peginterferon beta-1a in the ALLOW study. PATIENTS AND METHODS: Patients with relapsing multiple sclerosis treated with intramuscular interferon (IFN) beta-1a or SC IFN beta-1a or beta-1b remained on their current therapy for a 4-week run-in period, followed by a switch to SC peginterferon beta-1a 125 mcg every 2 weeks for 48 weeks. Treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM), which covers effectiveness, side effects, convenience, and global satisfaction. Patients completed the TSQM at baseline (prior to starting the 4-week run-in period) and 4, 12, 24, 36, and 48 weeks after switching, and scores were analyzed for the overall population and compared to baseline. Patients reported the severity of flu-like symptoms (FLS) at baseline and with each peginterferon beta-1a injection; clinicians evaluated the occurrence of injection-site reactions (ISRs) after the first dose of peginterferon beta-1a and every 12 weeks thereafter. TSQM scores were stratified by the presence of FLS or ISRs during the study period and by prior IFN therapy use. RESULTS: For the overall population (n=194), convenience and global satisfaction scores significantly improved from baseline at all time points, and side effect satisfaction scores significantly improved up to week 36. Convenience scores significantly improved regardless of FLS, ISRs, or prior IFN therapy. Patients without FLS during the study period showed significant improvements in global satisfaction, but not side effect satisfaction, versus those with FLS. Patients switching from SC IFN therapies achieved greater improvements in treatment satisfaction than patients who switched from intramuscular IFN beta-1a. CONCLUSIONS: Switching relapsing multiple sclerosis patients to SC peginterferon beta-1a from other IFN therapies significantly improved treatment satisfaction and convenience.

Development and Validation of Algorithms to Identify Statin Intolerance in a US Administrative Database.

OBJECTIVES: To develop and validate algorithms to define statin intolerance (SI) in an administrative database using electronic medical records (EMRs) as the reference comparison. METHODS: One thousand adults with one or more qualifying changes in statin therapy and one or more previous diagnoses of hyperlipidemia, hypercholesterolemia, or mixed dyslipidemia were identified from the Henry Ford Health System administrative database. Data regarding statin utilization, comorbidities, and adverse effects were extracted from the administrative database and corresponding EMR. Patients were stratified by cardiovascular (CV) risk. SI was classified as absolute intolerance or titration intolerance on the basis of changes in statin utilization and/or the occurrence of adverse effects and laboratory testing for creatine kinase. Measures of concordance (Cohen's kappa [κ]) and accuracy (sensitivity, specificity, positive predictive value [PPV], and negative predictive value) were calculated for the administrative database algorithms. RESULTS: Half of the sample population was white, 52.9% were women, mean age was 60.6 years, and 35.7% were at high CV risk. SI was identified in 11.5% and 14.0%, absolute intolerance in 2.2% and 3.1%, and titration intolerance in 9.7% and 11.8% of the patients in the EMR and the administrative database, respectively. The algorithm identifying any SI had substantial concordance (κ = 0.66) and good sensitivity (78.1%), but modest PPV (64.0%). The titration intolerance algorithm performed better (κ = 0.74; sensitivity 85.4%; PPV 70.1%) than the absolute intolerance algorithm (κ = 0.40; sensitivity 50%; PPV 35.5%) and performed best in the high CV-risk group (n = 353), with robust concordance (κ = 0.73) and good sensitivity (80.9%) and PPV (75.3%). CONCLUSIONS: Conservative but comprehensive algorithms are available to identify SI in administrative databases for application in real-world research. These are the first validated algorithms for use in administrative databases available to decision makers.

Impact of dronedarone treatment on healthcare resource utilization in patients with atrial fibrillation/flutter.

BACKGROUND: 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 demonstrated a significant reduction (26%) in the rate of first cardiovascular (CV) hospitalization in dronedarone-treated patients with paroxysmal or persistent atrial fibrillation/flutter (AF/AFL). ATHENA was the first trial to demonstrate a CV outcomes benefit, specifically reduced CV hospitalizations, with an antiarrhythmic drug. The objective of this study was to assess the impact of dronedarone treatment on healthcare resource utilization among real-world patients with AF/AFL in United States clinical practice. METHODS: This retrospective cohort study used claims data from the MarketScan® databases (Truven Health, Durham, NC, USA) to identify patients with ≥2 concurrent de novo pharmacy claims for dronedarone (≥180 days' total supply) between June 2009 and March 2011, and with an AF/AFL diagnosis and no heart failure-related hospitalization during the 12 months preceding the initial (index) dronedarone claim. Annualized inpatient and outpatient resource utilization were compared between the pre-index (baseline) and post-index (follow-up) periods. RESULTS: In total, 5,656 AF/AFL patients were prescribed dronedarone for ≥6 months and were followed for mean (standard deviation) 11.9 (4.7) months. Reductions in mean numbers of annualized all-cause, CV- and AF-related hospitalizations (~40-45%), and emergency department visits (~30-45%) were realized. These benefits were offset by increases in office visits (~10-30%) and AF-related prescription claims (74%) after dronedarone initiation. The sub-cohort of patients switching to dronedarone from Prior Rhythm-Control therapy (n=2,080) showed similar reductions in hospital and emergency department events. CONCLUSIONS: This study suggests that dronedarone use in real-world practice, as in the ATHENA trial, results in substantial reductions in hospital admissions, both in first-line and second-line antiarrhythmic treatment settings.

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.

Comparative effectiveness of antiarrhythmic drugs on cardiovascular hospitalization and mortality in atrial fibrillation.

AIM: To assess, through a systematic review, evidence for the effects of antiarrhythmic drugs (AADs) on cardiovascular (CV) hospitalization and mortality. MATERIALS & METHODS: English language articles were identified using MEDLINE, EMBASE and the Cochrane Clinical Trial Registry and were screened for study applicability and methodological quality. RESULTS: Out of 3526 identified studies, 38 were selected for analysis (19 evaluated individual AADs, 13 compared rate- versus rhythm-control strategies, and 6 evaluated multiple AADs but did not report outcomes for individual agents). None of the studies examining individual AADs employed the CV hospitalization end point used in ATHENA (the reference trial). There were no head-to-head comparisons of individual AADs on CV hospitalization. Most high-quality studies used multidrug rate- versus rhythm-control strategies. CONCLUSION: Assessment of the comparative effectiveness of individual AADs on CV hospitalization and mortality end points is not possible with the current evidence.

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.

Predictors of progression of recently diagnosed atrial fibrillation in REgistry on Cardiac Rhythm DisORDers Assessing the Control of Atrial Fibrillation (RecordAF)-United States cohort.

The progression of atrial fibrillation (AF) to a more sustained form is associated with increased symptoms and morbidity. The aims of the REgistry on Cardiac Rhythm DisORDers Assessing the Control of Atrial Fibrillation (RecordAF)-United States (US) cohort study were to identify the risk factors of AF progression and the effects of management approaches. RecordAF is the first worldwide, 1-year observational study of the treatment of community-based patients with recent-onset AF. We assessed AF progression at 12 months in the US cohort. AF progression was defined as a change of AF to a more sustained form (either paroxysmal becoming persistent or permanent, or persistent becoming permanent). The US cohort included 955 patients, with mean age of 68.9 years; 56.8% were men and 88.8% were white. At entry, 59.6% of patients were selected for rate-control and 40.4% for rhythm-control therapy. At 12 months, the management strategy was unchanged for 68.2% of the patients in the rate- and 77.7% of the patients in the rhythm-control groups. Overall, AF progression had occurred in 18.6% of patients at 12 months. The progression rate was significantly greater in the rate-control (27.6%) than in the rhythm-control (5.8%) group (p <0.001). Progression to permanent AF occurred in 16.4% of patients. In addition to a rate-control strategy, older age, AF rhythm at entry, persistent AF at baseline, and a history of stroke or transient ischemic attack independently predicted AF progression. Rate control was associated with AF progression, with a propensity score adjusted odds ratio of 2.67 (p <0.001). In conclusion, rate control was the preferred treatment of recent-onset AF in the US but was associated with more AF progression than rhythm control.

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.

One-year treatment persistence and potential adverse events among patients with atrial fibrillation treated with amiodarone or sotalol: a retrospective claims database analysis.

BACKGROUND: The risk-benefit profile of antiarrhythmic drugs (AADs) affects the choice of pharmacotherapy for maintenance of sinus rhythm. Adverse events (AEs) associated with AADs may influence patient compliance and compromise the management of atrial fibrillation (AF). There are limited data on the incidence of AEs or persistence with AADs outside the clinical trial environment. OBJECTIVE: This study provides treatment persistence and AE data for patients with AF receiving treatment with amiodarone or sotalol, 2 of the most widely used AADs in the United States. METHODS: In this retrospective cohort study, patients satisfying the following criteria were identified from the US MarketScan claims databases: (1) age ≥18 years with a pharmacy claim for oral amiodarone or sotalol between 2004 and 2007; (2) ≥1 inpatient/outpatient medical claim with an AF diagnosis <90 days before the earliest (index) pharmacy claim; and (3) ≥12 months' continuous enrollment before and after the index pharmacy claim. Prespecified AE rates were compared between treatment cohorts during active treatment. RESULTS: Among 77,093 AF patients with ≥1 claim for amiodarone or sotalol, 3459 met all inclusion criteria (mean age, 70.8 years; 61.6% male; mean Charlson Comorbidity Index [CCI], 1.58), of whom 2392 received amiodarone (mean age, 72.2 years; 62.5% male; mean CCI, 1.8) and 1067 received sotalol (mean age, 67.5 years; 59.7% male; mean CCI, 1.1). Persistence was higher among the sotalol cohort than the amiodarone cohort (53.2% vs 30.6% at 12 months; P < 0.001). Postindex versus preindex comparisons revealed increases in cardiovascular AE rates in both cohorts. Intercohort comparisons showed higher rates of cardiovascular AEs (594 vs 339 patients/1000 patient-years; P < 0.001) and pulmonary AEs (128 vs 61 patients/1000 patient-years; P < 0.001) during active amiodarone treatment. CONCLUSIONS: Among the population analyzed, patients with AF receiving amiodarone versus sotalol therapy had differing clinical characteristics. Patients experienced frequent AEs (particularly cardiovascular events) with amiodarone and sotalol, and many discontinued treatment during the first year.

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.