Risk Analysis of Respiratory Syncytial Virus Among Infants in the United States by Birth Month.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality among U.S. infants. A child's calendar birth month determines their age at first exposure(s) to RSV. We estimated birth month-specific risk of medically attended (MA) RSV lower respiratory tract infection (LRTI) among infants during their first RSV season and first year of life. METHODS: We analyzed infants born in the USA between July 2016 and February 2020 using three insurance claims databases (two commercial, one Medicaid). We classified infants' first MA RSV LRTI episode by highest level of care incurred (outpatient, emergency department, or inpatient), employing specific and sensitive diagnostic coding algorithms to define index RSV diagnoses. In our main analysis we focused on infants' first RSV season. In our secondary analysis we compared the risk of MA RSV LRTI during infants' first RSV season to that of their first year of life. RESULTS: Infants born from May through September generally had the highest risk of first-season MA RSV LRTI-approximately 6%-10% under the specific RSV index diagnosis definition and 16%-26% under the sensitive. Infants born between October and December had the highest risk of RSV-related hospitalization during their first season. The proportion of MA RSV LRTI events classified as inpatient ranged from 9%-54% (specific) and 5%-33% (sensitive) across birth month and comorbidity group. Through the first year of life, the overall risk of MA RSV LRTI is comparable across birth months within each claims database (6%-11% under the specific definition, 17%-30% under the sensitive), with additional cases progressing to care at outpatient or ED settings. CONCLUSIONS: Our data support recent national recommendations for the use of nirsevimab in the USA. For infants born at the tail end of an RSV season who do not receive nirsevimab, a dose administered prior to the onset of their second RSV season could reduce the incidence of outpatient and ED-related events.

Prevalence and impact of antipsychotic discontinuation among commercially-insured patients with bipolar disorder.

BACKGROUND: Antipsychotic discontinuation is common among patients with bipolar disorder, especially when psychotic symptoms are remitted. This analysis describes the prevalence, predictors, and economic impact of antipsychotic discontinuation among patients with bipolar disorder. METHODS: A retrospective, observational study was conducted using administrative claims data in the IBM MarketScan Commercial Database. Patients with ≥1 claim with a diagnosis for bipolar disorder (manic or mixed) and newly-initiating antipsychotic therapy between 1 January 2011 and 30 June 2016 were included. Baseline characteristics were assessed in the 12 months prior to the initiation. Outcomes were assessed during a 24-month follow-up. Discontinuation of antipsychotic therapy was utilized as a predictor of healthcare costs in models adjusted for baseline characteristics. Using limited set of variables in the claims database, predictors of discontinuation were also assessed. RESULTS: A total of 18,259 commercially-insured patients were identified as initiators of antipsychotics. Common comorbidities among the cohorts included major depressive disorder and dyslipidemia. Discontinuation was very common among these patients (85%). Major depressive disorder, drug abuse, and other substance abuse/dependency were predictive of discontinuation. Controlling for differences in baseline characteristics, discontinuation was associated with 33% higher inpatient and emergency visit costs (p <.001) among those using these services, and 24% higher total healthcare costs (p <.001) for the overall cohort. CONCLUSIONS: Most patients with bipolar mania or mixed states discontinue antipsychotic treatment in less than 2 years. Antipsychotic discontinuation contributes to excess healthcare costs. Future research focusing on the reasons for discontinuation and tailoring disease management based on comorbidities may inform adherence improvement initiatives.

Medically Attended Illness due to Respiratory Syncytial Virus Infection Among Infants Born in the United States Between 2016 and 2020.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization in the United States. Preterm infants and those with select comorbidities are at highest risk of RSV-related complications. However, morbidity due to RSV infection is not confined to high-risk infants. We estimated the burden of medically attended (MA) RSV-associated lower respiratory tract infection (LRTI) among infants in the United States. METHODS: We analyzed commercial (MarketScan Commercial [MSC], Optum Clinformatics [OC]), and Medicaid (MarketScan Medicaid [MSM]) insurance claims data for infants born between April 2016 and February 2020. Using both specific and sensitive definitions of MA RSV LRTI, we estimated the burden of MA RSV LRTI during infants' first RSV season, stratified by gestational age, comorbidity status, and highest level of medical care associated with the MA RSV LRTI diagnosis. RESULTS: According to the specific definition 75.0% (MSC), 78.6% (MSM), and 79.6% (OC) of MA RSV LRTI events during infants' first RSV season occurred among term infants without known comorbidities. CONCLUSIONS: Term infants without known comorbidities account for up to 80% of the MA RSV LRTI burden in the United States during infants' first RSV season. Future prevention efforts should consider all infants.

Cardiometabolic outcomes among schizophrenia patients using antipsychotics: the impact of high weight gain risk vs low weight gain risk treatment.

OBJECTIVE: Evaluate the prevalence of cardiometabolic conditions among schizophrenia patients before and incidence after initiation of high (HWGR) and low weight gain risk (LWGR) antipsychotic (AP) regimens. METHODS: A retrospective observational cohort study was conducted using administrative claims data from the IBM® MarketScan Commercial and Multi-State Medicaid Databases. Patients with > 1 medical claim with a diagnosis for schizophrenia and newly initiating AP therapy between 1/1/11-6/30/16 were included. Baseline characteristics were assessed in the 12-months before AP initiation; outcomes over 24-months following AP initiation. Patients were characterized by the AP regimen initiated at the index date. Adherence was defined by a medication possession ratio > 0.8 (medication on hand for 80% of follow-up). Multivariate modeling identified predictors of index AP weight gain risk profile and post-index dyslipidemia. RESULTS: Two thousand seven hundred forty-eight commercially-insured and 8,748 Medicaid patients met the inclusion criteria. A majority of patients initiated on atypical AP and approximately 30% were adherent to their index AP regimen. Within both payers, patients indexing on LWGR AP regimens were more likely to have pre-index diagnoses of cardiometabolic conditions including hypertension, dyslipidemia, and diabetes. Significant predictors of post-index dyslipidemia included AP adherence and pre-index diabetes. Within both payers, odds of initiating HWGR AP regimens were higher among patients with evidence of drug abuse. CONCLUSIONS: There is unmet need for reducing cardiometabolic consequences for patients on AP therapy and this analysis provides evidence that cardiometabolic conditions often develop during early stages of AP therapy. However, this does not appear to be related to the weight gain risk profile of the AP regimen.

Association of physician specialty with psoriatic arthritis treatment and costs.

OBJECTIVES: To describe current psoriatic arthritis treatment and costs by provider specialty using real-world claims data. STUDY DESIGN: Observational, retrospective cohort study of patients in the IBM MarketScan Commercial and supplemental Medicare databases. METHODS: Eligible patients had newly diagnosed psoriatic arthritis with 12 months of continuous enrollment pre- and post index date for their initial claim. Patients were assigned to 1 of 5 provider specialty cohorts. During the 1-year follow-up period, we collected psoriatic arthritis treatment agent and regimen type and total annual medical and health care costs. We used multivariate regression models to determine the conditional associations of provider specialty with costs. RESULTS: A total of 2132 patients with incident psoriatic arthritis qualified. Most providers were rheumatologists (n = 1365; 64%). Rheumatologists commonly prescribed oral small molecules (methotrexate, 56.3% of prescriptions; sulfasalazine, 8.6%; apremilast, 7.0%) as the index therapy, whereas 23.8% of prescriptions were for tumor necrosis factor inhibitors (adalimumab, 14.2%; etanercept, 7.9%; and infliximab, 1.7%). Compared with other specialists, dermatologists prescribed biologics and other specialty drugs more frequently-adalimumab (32.7%), apremilast (14.3%), etanercept (11.6%), and ustekinumab (8.8%)-and methotrexate less frequently (30.6%). The greatest unadjusted median health care costs were observed among dermatologists ($45,548) compared with rheumatologists ($30,411), primary care physicians ($29,927), rheumatologists/dermatologists ($27,393), and other specialists ($27,774). However, after adjusting for patient-level factors, multivariate regression analyses found that provider specialty was not associated with higher health care costs. CONCLUSIONS: In patients with newly diagnosed psoriatic arthritis, physician specialty was associated with different medication choices but not costs.

Healthcare resource utilization and costs among children with cystic fibrosis in the United States.

BACKGROUND: Adverse health impacts of cystic fibrosis (CF) can be present in children before respiratory complications are observed. Children with CF show progressive health decline, with increasing lung function decline in adolescence. This study aims to quantify the healthcare resource utilization (HCRU) and costs attributable to CF by comparing children with CF with the general pediatric population. METHODS: This retrospective, cross-sectional, observational study compared HCRU and costs among children with CF in the US with demographically similar children without CF (comparison group) over a 12-month period using administrative claims data spanning 2010-2017. Analyses were conducted by insurance type (commercially insured [COM] and Medicaid insured [MED]) and stratified by age (<2 years, 2 to <6 years, 6 to <12 years, and 12-17 years). RESULTS: Children with CF (2831 COM and 1896 MED) were matched to children in the comparison group (8493 COM and 5688 MED). Higher prevalence of comorbidities was seen in children with CF versus the comparison group across all ages. Across all ages, HCRU attributable to CF was substantial (higher hospitalization rates, more outpatient and emergency room visits, and greater use of prescription medications), and there were higher associated costs (all p values < .05), in COM and MED populations. HCRU and costs attributable to CF were highest for children aged 12-17 years. CONCLUSIONS: Substantial HCRU and costs are evident among children with CF across all ages, starting as young as infancy, with highest HCRU and costs among adolescents. Effective treatments from an early age are needed for children with CF.

Long-Term Impact of Ivacaftor on Healthcare Resource Utilization Among People with Cystic Fibrosis in the United States.

INTRODUCTION: Ivacaftor was first approved in 2012 for the treatment of a select population of individuals with cystic fibrosis (CF), a rare, life-shortening genetic disease. Reductions in healthcare resource utilization (HCRU) associated with ivacaftor have been observed during limited follow-up and for selected outcomes in real-world studies. This study aimed to further describe the long-term impact of ivacaftor treatment on multiple measures of HCRU among people with CF (pwCF). METHODS: This retrospective study used US commercial and Medicaid claims data from 2011-2018. We included pwCF ≥ 6 years of age with ≥ 1 claim for ivacaftor and 12 months of continuous health plan enrollment before ivacaftor initiation ("pre-ivacaftor" period) who also had 36 months of continuous enrollment and persistent ivacaftor use (i.e., no gap ≥ 90 days between refills) following initiation ("post-ivacaftor" period). We compared comorbidities occurring pre-ivacaftor versus the last 12 months post-ivacaftor. HCRU outcomes included medication use, inpatient admissions, and outpatient office visits. We compared medication use pre-ivacaftor versus the last 12 months post-ivacaftor and inpatient admissions and outpatient office visits pre-ivacaftor versus the post-ivacaftor period annualized across 36 months. RESULTS: Seventy-nine pwCF met all criteria, including persistent ivacaftor use during the post-ivacaftor period. Ivacaftor treatment was associated with a significant reduction in pneumonia prevalence (10.1% vs. 26.6%; p < 0.001) and significantly fewer mean [SD] antibiotics claims (8.0 [7.3] vs. 12.3 [11.1]; p < 0.001) in the last 12 months post-ivacaftor versus pre-ivacaftor. In comparing the 36-month post-ivacaftor period to the pre-ivacaftor period, we also observed fewer mean [SD] annual inpatient admissions (0.2 [0.4] vs. 0.4 [0.7]), CF-related inpatient admissions (0.1 [0.2] vs. 0.2 [0.5]), and outpatient office visits (8.8 [4.9] vs. 9.9 [5.4]) (all, p < 0.05). CONCLUSION: Long-term ivacaftor treatment reduced HCRU, consistent with trends observed in prior real-world studies. Our results support the sustained, long-term value of ivacaftor treatment in reducing CF burden.

Real-world treatment patterns, healthcare resource utilisation and costs in patients with systemic lupus erythematosus treated with belimumab: a retrospective analysis of claims data in the USA.

Objective: To examine the effects of belimumab initiation on healthcare resource utilisation (HCRU) and costs in SLE. Methods: This retrospective observational cohort study used healthcare administrative claims data from the IBM MarketScan Commercial Claims and Encounters Database to identify patients with SLE billing codes who received ≥1 intravenous belimumab infusion between March 2011 and December 2015. The first belimumab administration was the 'index date'. During the 6-month postindex period, nine belimumab infusions were recommended: three during the initiation period and six during the maintenance period. HCRU and cost data for inpatient admissions, emergency department visits, physician office visits, hospital-based outpatient visits, laboratory services, other outpatient services and outpatient pharmacy prescriptions were compared in the 6-month pre/postindex periods. Results: Of the 1879 patients with SLE included, 43% received ≥3 intravenous initiation administrations. An average of 5.3 (SD: 2.4) of the nine recommended belimumab administrations were received within 6 months. In the 6-month preindex versus postindex periods, significant reductions were noted for inpatient hospitalisations (18% vs 9%, p<0.001; mean visits: 0.3 vs 0.14, p<0.001) and emergency department visits (40% vs 24%, p<0.001; mean visits; 3.53 vs 1.96, p<0.001). Mean total costs were higher in the 6-month postindex versus preindex period ($41 426 vs $29 270; p<0.001). Conclusions: In this study of real-world intravenous belimumab for SLE, adherence to recommended infusion schedules was low. Outpatient healthcare and associated costs were higher in the 6 months after belimumab was initiated, although inpatient costs were lower. Reasons for non-adherence with belimumab and implications should be investigated.

The burden of cystic fibrosis in the Medicaid population.

PURPOSE: To conduct an analysis describing clinical characteristics, pulmonary exacerbation (PEx) events, and health care resource utilization among Medicaid-insured patients with cystic fibrosis (CF). PATIENTS AND METHODS: A retrospective analysis of the Truven Health MarketScan® Medicaid Multi-State administrative claims database (2010-2014) was undertaken. Patients aged ≥6 years with a CF diagnosis, continuously enrolled for 12 months, were identified. Demographics, comorbidities, PEx events, and health care resource utilization and costs over a 12-month enrollment period were analyzed for all patients and by age groups. RESULTS: In total, 1196 patients with CF aged ≥6 years were identified from a sample size of approximately 10 million Medicaid patients. Mean (SD) age was 16.1 (8.8) years. A greater proportion of patients were in younger age groups (6-11 years: 35.5%, 12-17 years: 29.1%, 18-26 years: 25.6%, 27-34 years: 6.7%, ≥35 years: 3.2%). Across all age groups, approximately 90% of patients had at least 1 PEx event; 50.7% of those had a PEx event involving treatment with intravenous antibiotics, and 42.8% required hospitalization. PEx recurrence was frequent: 55.7% of all patients experienced ≥3 PEx events during 1 year. Mean (SD) health care expenditures during a PEx event rose with increasing age, ranging from US$44,589 (US$139,024) to US$116,169 (US$387,752). Overall health care resource utilization was high among patients with CF; 47.2% of the population required an inpatient admission, and 26.8% had subsequent hospitalizations totaling 29.1 days per year in hospital. CONCLUSION: High rates of PEx, hospitalizations, and time spent in hospital demonstrate the significant health care burden of CF among Medicaid beneficiaries.

Economic analysis and budget impact of clostridial collagenase ointment compared with medicinal honey for treatment of pressure ulcers in the US.

OBJECTIVES: Pressure ulcer (PU) treatment poses significant clinical and economic challenges to health-care systems. The aim of this study was to assess the cost-effectiveness and budget impact of enzymatic debridement with clostridial collagenase ointment (CCO) compared with autolytic debridement with medicinal honey (MH) for PU treatment from a US payer/Medicare perspective in the hospital outpatient department setting. METHODS: A cost-effectiveness analysis using a Markov model was developed using a 1-week cycle length across a 1-year time horizon. The three health states were inflammation/senescence, granulation/proliferation (ie, patients achieving 100% granulation), and epithelialization. Data sources included the US Wound Registry, Medicare fee schedules, and other published clinical and cost studies about PU treatment. RESULTS: In the base case analysis over a 1-year time horizon, CCO was the economically dominant strategy (ie, simultaneously conferring greater benefit at less cost). Patients treated with CCO experienced 22.7 quality-adjusted life weeks (QALWs) at a cost of $6,161 over 1 year, whereas MH patients experienced 21.9 QALWs at a cost of $7,149. Patients treated with CCO achieved 11.5 granulation weeks and 6.0 epithelization weeks compared with 10.6 and 4.4 weeks for MH, respectively. The number of clinic visits was 40.1 for CCO vs 43.4 for MH, and the number of debridements was 12.3 for CCO compared with 17.6 for MH. Probabilistic sensitivity analyses determined CCO dominant in 72% of 10,000 iterations and cost-effective in 91%, assuming a benchmark willingness-to-pay threshold of $50,000/quality-adjusted life year ($962/QALW). The budget impact analysis showed that for every 1% of patients shifted from MH to CCO, a cost savings of $9,883 over 1 year for a cohort of 1,000 patients was observed by the payer. CONCLUSION: The results of these economic analyses suggest that CCO is a cost-effective, economically dominant alternative to MH in the treatment of patients with PUs in the hospital outpatient department setting.

Retrospective analysis to describe associations between tumor necrosis factor alpha inhibitors and COPD-related hospitalizations.

BACKGROUND: Limited information exists on the impact of tumor necrosis factor inhibition on COPD exacerbations. This retrospective study characterized this impact among COPD patients with underlying autoimmune conditions, exposed to tumor necrosis factor inhibitors (TNFi) and/or non-biologic disease-modifying antirheumatic drugs (DMARDs). PATIENTS AND METHODS: Adult COPD patients with ≥1 diagnosis for rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) before or within 6 months following the index COPD diagnosis were identified from the Truven Health MarketScan® databases. Patients were required to have a second claim for RA, PsO, PsA, AS, or DMARD use (biologic or non-biologic) prior to or up to 6 months following the index date. Incidence of COPD-related hospitalizations and emergency room (ER) visits was evaluated in relation to treatment with TNFi and/or DMARDs and other potential risk factors. RESULTS: The study cohort included 40,687 patients (untreated, 37.7%; non-biologic DMARD, 35.4%; TNFi + non-biologic DMARD, 18%; TNFi, 8.8%). The proportion of patients with a COPD-related hospitalization and the incidence of COPD-related hospitalization (per 100 person-years) were lowest in the TNFi cohort (8.6%; 3.54, 95% confidence interval [CI]: 3.16-3.95) and the TNFi + non-biologic DMARD cohort (8.4%; 2.85, 95% CI: 2.63-3.08). In multivariate models, treatment with TNFi + non-biologic DMARD reduced the risk of COPD-related hospitalization or ER visits by 32% relative to non-biologic DMARDs (hazard ratio: 0.68; 95% CI: 0.61-0.75). CONCLUSION: In real-world settings, TNFi monotherapy confers similar risk for COPD-related hospitalization or ER visits as a non-biologic DMARD. Decreased risk was found among those treated with both TNFi and a non-biologic DMARD.

Healthcare resource utilization associated with ivacaftor use in patients with cystic fibrosis.

OBJECTIVE: Ivacaftor was approved in 2012 to treat patients with cystic fibrosis (CF) with specific CFTR gene mutations. The objective of this analysis was to analyze the impact of ivacaftor on health resource utilization through analysis of claims data. METHODS: Patients diagnosed with CF aged ≥6 years prescribed ivacaftor between January 1, 2012 and July 31, 2014 with ≥12 months of continuous insurance coverage prior to and following the prescription were identified. All-cause and CF-specific healthcare resource utilization during the pre- and post-prescription periods and ivacaftor adherence levels were studied. RESULTS: The 79 identified patients had a mean age of 20.8 years, and 54% were female. The proportion of patients with inpatient admissions (all-cause and CF-related) was significantly higher in the pre index compared to post index period (p ≤ 0.05). Mean ivacaftor medication possession ratio was 0.8 (SD = 0.3), and 73% of patients had a medication possession ratio >0.80. LIMITATIONS: Only a small number of patients met the inclusion criteria. Additionally, claims data may contain errors or inconsistencies and cannot be used to determine if medications were taken as prescribed. CONCLUSIONS: Ivacaftor therapy was associated with significant reductions in hospitalizations along with high rates of adherence to treatment over 12 months.

Mapping of Multiple Sclerosis Walking Scale (MSWS-12) to five-dimension EuroQol (EQ-5D) health outcomes: an independent validation in a randomized control cohort.

BACKGROUND: Mapping of patient-reported outcomes to the five-dimension EuroQol (EQ-5D) health index is increasingly being used for understanding the relationship of outcomes to health states and for predicting utilities that have application in economic evaluations. The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported outcome that assesses the impact of walking impairment in people with MS. An equation for mapping the MSWS-12 to the EQ-5D was previously developed and validated using a North American Research Committee on MS (NARCOMS) registry cohort. MATERIALS AND METHODS: This analysis retested the validity of the equation mapping the MSWS-12 to the three-level EQ-5D (EQ-5D-3L) by using an independent cohort of patients with MS enrolled in a randomized controlled trial. Mapping was evaluated at two separate time points (baseline and week 4) during the clinical trial. The mapping equation's performance was subsequently assessed with mean absolute error (MAE) and root-mean-square error (RMSE) by comparing equation-based estimates to values elicited in the trial using the actual EQ-5D-3L questionnaire. RESULTS: The mapping equation predicted EQ-5D-3L values in this external cohort with reasonable precision at both time points (MAE 0.116 and RMSE 0.155 at baseline; MAE 0.105 and RMSE 0.138 at week 4), and was similar to that reported in the original NARCOMS cohort (MAE 0.109 and RMSE 0.145). Also as observed in the original NARCOMS cohort, the mapping equation performed best in patients with EQ-5D-3L values between 0.50 and 0.75, and poorly in patients with values <0.50. CONCLUSION: The mapping equation performed similarly in this external cohort as in the original derivation cohort, including a poorer performance in MS patients with more severe health-state severity.

Persistance and Compliance with Osteroporosis Therapies Among Women in a Commercially Insured Population in the United States.

BACKGROUND: Prior research has shown that rates of persistence and compliance with osteoporosis therapies are associated with significantly fewer vertebral, nonvertebral, and hip fractures. A number of studies have examined medication-taking behavior with oral bisphosphonates and teriparatide, and these 1-year persistence rates have ranged from 39.9% to 56.7%. Limited real-world data are available regarding persistence and compliance rates with newer therapies such as denosumab, a RANK ligand inhibitor administered every 6 months as a subcutaneous injection.  OBJECTIVE: To assess persistence and compliance rates over 1 year with newly initiated osteoporosis therapies, including denosumab, alendronate, ibandronate, risedronate, raloxifene, and teriparatide, within a cohort of commercially insured women.  METHODS: Health insurance claims data derived from Truven Health Analytics MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases (2010-2013) were used to conduct this retrospective cohort study. Adult females aged 18 years and older newly initiated on denosumab, raloxifene, teriparatide, or oral bisphosphonates (alendronate, ibandronate, or risedronate) between January 1, 2012, and March 31, 2012, were identified for inclusion. The date of the first qualifying osteoporosis prescription claim was defined as the index date. Patients were required to have at least 24 months of pre-index and at least 12 months of post-index continuous enrollment with medical and pharmacy benefits. Outcomes of patients initiating zoledronic acid (administered intravenously once yearly) were not assessed because a 12-month follow-up period would be insufficient for tracking persistence and compliance for this medication. Patients with Paget's disease of the bone, osteogenesis imperfecta, hypercalcemia, malignant cancer and metastasis, human immunodeficiency virus, and patients receiving preventive treatment for risk of breast cancer or denosumab in the pre-index period were excluded from the study. A subcohort of women aged 50 years and older at high risk for fracture (indicated by 1 or more of the following: aged ≥ 70 years, a pre-index fracture, or pre-index use of osteoporosis therapy that was discontinued at least 3 months prior to index) was analyzed separately. Propensity score weighting was used to adjust for differences in baseline demographic and clinical characteristics. Persistence, indicated by continuous use of the index therapy without a gap of 60 days or more; medication coverage ratio (MCR), the proportion of days covered by the index therapy; and compliance, defined as an MCR ≥ 0.80, were assessed during the 12-month follow-up. Logistic regression was used to estimate the odds of persistence and compliance for the treatment groups of interest. RESULTS: 10,863 female patients newly initiating osteoporosis medications (mean [SD] age: 66.2 [11.5] years) were identified. In the pre-index period, 35.8% of patients had a diagnosis of osteoporosis, while 11.5% had a diagnosis of osteopenia. Pre-index osteoporosis treatment was identified in 29.1% of patients, and 13.6% had an osteoporosis-related fracture in the pre-index period. Propensity score weight-adjusted 12-month persistence with the index medication varied from 28.9% to 35.1% for oral bisphosphonate users, 42.0% for raloxifene users, 59.1% for teriparatide users, and 68.3% for denosumab users (P less than 0.0001). The adjusted mean [SD] MCR was highest among patients treated with denosumab (0.83 [0.21]), followed by teriparatide (0.67 [0.31]), raloxifene, (0.57 [0.34]), ibandronate (0.54 [0.32]), alendronate (0.51 [0.33]), and risedronate (0.46 [0.33]; P less than 0.0001). The odds of being persistent and compliant across treatments favored denosumab (OR = 1.59 to 5.56, P less than 0.05 for persistence; OR = 2.44 to 7.69, P less than 0.0001 for compliance). Results were similar in the subcohort of women aged 50 years and older at high risk for fracture (n = 6,187; mean [SD] age: 71.9 [10.9] years). The odds of being persistent and compliant across treatments also favored denosumab (OR = 1.62 to 5.75, P less than 0.0001 for persistence; OR = 2.36 to 7.25, P less than 0.0001 for compliance). CONCLUSIONS: In a U.S. setting, rates of persistence and compliance over 12 months were higher among women initiating denosumab compared with those initiating other osteoporosis therapies.

Common flaws exist in published cost-effectiveness models of pharmacologic stroke prevention in atrial fibrillation.

OBJECTIVES: Decision makers use models to assist in evaluating the cost-effectiveness of pharmacologic stroke prevention in atrial fibrillation (SPAF). STUDY DESIGN AND SETTING: We performed a search of databases through October 3, 2012 to identify pharmacologic SPAF cost-effectiveness models. RESULTS: Of 30 identified models, 28 included warfarin, but only 60% assessed the impact of warfarin control on conclusions. Aspirin, dual antiplatelet, and newer anticoagulants were included in 41%, 10%, and 63% of models, respectively. Models used similar structures but included varying health states and made varying assumptions. They rarely reported performing a literature search to identify anticoagulant-specific inputs and used similar and older sources. Sixteen models used a lone randomized trial to reflect the efficacy and safety of main comparisons. One-third of models claimed a societal perspective; however, none included indirect costs. Patients typically initiated anticoagulation in the sixth or seventh decade of life and are followed for their lifetimes. Almost 70% of incremental cost-effectiveness ratios were below reported willingness-to-pay thresholds. All used deterministic sensitivity analyses and 77% conducted Monte Carlo simulation. Less than half of the models were rated "high quality," yet were frequently published in high-impact journals. CONCLUSION: Pharmacologic SPAF cost-effectiveness models have been extensively reported, but many may have flaws giving reason for decision makers to use caution. We provide 10 recommendations to avoid common flaws in SPAF cost-effectiveness models.

Cost-effectiveness analysis of extended duration anticoagulation with rivaroxaban to prevent recurrent venous thromboembolism.

INTRODUCTION: Extended duration anticoagulation with rivaroxaban for an additional 6-12 months can reduce recurrent venous thromboembolic events (VTE) compared to placebo by ~82%, but at the detriment of increased bleeding. We sought to estimate the cost-effectiveness of extended duration prophylaxis of recurrent VTE with rivaroxaban. MATERIAL AND METHODS: A Markov model was developed to estimate the cost-effectiveness of extended duration rivaroxaban, 20mg daily, compared to placebo using a Medicare perspective, a one-monthcycle length and a 40-year time horizon. The model assumed a cohort of 58-year-old patients who had already completed an initial 6-12 months of anticoagulation with rivaroxaban or a vitamin K antagonist; and whom prescribers had clinical equipoise with respect to the need for continued anticoagulation. Data sources included EINSTEIN-Extension and other published studies of VTE. Outcomes included direct treatment costs (in 2013US$), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: Extended duration rivaroxaban resulted in higher treatment costs ($22,645 vs. $22,083) but yielded greater QALYs (16.167 vs. 16.134) as compared to placebo; corresponding to an ICER of $17,030/QALY gained. Our model was most sensitive to the baseline risk of bleeding and recurrent VTE, the hazard ratio of developing a recurrent event while on rivaroxaban and time horizon. Monte Carlo Simulation suggested rivaroxaban would be cost-effective in 66% of 10,000 iterations, assuming a willingness-to-pay threshold of $50,000/QALY. CONCLUSION: Despite the cost of rivaroxaban and an increased risk of bleeding, extending VTE treatment for an additional 6-12 months with rivaroxaban was found cost-effective compared to the placebo over a 40-year time horizon.

Impact of angina frequency on health utility values of patients with chronic stable angina.

BACKGROUND: Chronic angina is a profoundly symptomatic disease. We evaluated the relationship between angina frequency and health utility. METHODS: We used data from stable angina patients reporting ≥3 attacks/week enrolled in the Efficacy of Ranolazine in Chronic Angina (ERICA) trial. Angina frequency was classified using the Seattle Angina Questionnaire angina frequency (SAQAF) domain into no (100); monthly (61-99); weekly (31-60); and daily (0-30) angina. EuroQol (EQ)-5D health utility scores were derived from SAQ data using two mapping equations. Median EQ-5D utility scores for each SAQAF classification after the 6-week trial period were calculated (reported as: Equation 1/Equation 2). Changes in EQ-5D utility scores from baseline to end-of-trial for patients achieving and not achieving a ≥20-point improvement in SAQAF score and improving and not improving ≥1 SAQAF classification were compared. RESULTS: Median EQ-5D utility scores (n = 548) were 0.68/0.60. Compared to patients reporting no angina symptoms (n = 28; 0.89/0.87) patients reporting monthly (n = 188; 0.80/0.76), weekly (n = 283; 0.72/0.65) and daily (n = 49; 0.65/0.54) symptoms had poorer health utility (p < 0.001 for both equations). Patients improving ≥1SAQAF classification (n = 254/541, 47%) experienced a median 0.05/0.07 greater improvement in EQ-5D health utility compared to those not improving ≥1 classification (p < 0.001 for both equations). Patients improving ≥20-points on the SAQAF (n = 355/541, 66%) experienced a median 0.06/0.07 greater improvement in health utility compared to those not achieving a ≥20-point improvement (p < 0.001 for both). CONCLUSIONS: Chronic angina patient health utility decreases as angina frequency increases. Patients reporting clinically important improvement in angina frequency experience a tangible improvement in health utility. CLINICAL TRIAL REGISTRATION: NCT00091429.

Cost-effectiveness of ranolazine added to standard-of-care treatment in patients with chronic stable angina pectoris.

Ranolazine has been shown to decrease angina pectoris frequency and nitroglycerin consumption. We assessed the cost-effectiveness of ranolazine when added to standard-of-care (SoC) antianginals compared with SoC alone in patients with stable coronary disease experiencing ≥3 attacks/week. A Markov model utilizing a societal perspective, a 1-month cycle length, and a 1-year time horizon was developed to estimate costs (2013 US$) and quality-adjusted life years (QALYs) for patients receiving and not receiving ranolazine. Patients entered the model in 1 of the 4 angina frequency health states based upon Seattle Angina Questionnaire angina frequency (SAQAF) scores (100=no; 61 to 99=monthly; 31 to 60=weekly; and 0 to 30=daily angina) and were allowed to transition between states or to death based upon probabilities derived from the Efficacy of Ranolazine in Chronic Angina and other studies. Patients not responding to ranolazine in month 1 (not improving ≥1 SAQAF health state) were assumed to discontinue ranolazine and behave like SoC patients. Ranolazine patients lived a mean of 0.700 QALYs at a cost of $15,661. Those not receiving ranolazine lived 0.659 QALYs and at a cost of $14,321. The incremental cost-effectiveness ratio (ICER) for the addition of ranolazine was $32,682/QALY. The ICER was most sensitive to ranolazine cost but only exceeded $50,000/QALY when the cost of ranolazine increased >32% above base case. The ICER remained <$50,000/QALY when indirect costs were excluded, and mortality rates were assumed equivalent between SAQAF health states. Monte Carlo simulation found ranolazine cost-effective in 97% of 10,000 iterations at a $50,000/QALY willingness-to-pay threshold. In conclusion, ranolazine added to SoC is cost-effective in patients with weekly or daily angina.

Universal versus platelet reactivity assay-driven use of P2Y12 inhibitors in acute coronary syndrome patients: cost-effectiveness analyses for six European perspectives.

Platelet reactivity assays (PRAs) can predict patients' likely response to clopidogrel. As ticagrelor and prasugrel are typically considered first-line agents for acute coronary syndrome in Europe, we assessed the cost-effectiveness of universal compared to PRA-driven selection of these agents. A Markov model was used to calculate five-year costs (2013£/€), quality-adjusted life-years and incremental cost-effectiveness ratios (ICERs) for one-year of universal ticagrelor or prasugrel (given to all) compared to each agents' corresponding PRA-driven strategy (ticagrelor/prasugrel in those with high platelet reactivity [HPR, >208 on the VerifyNow P2Y12 assay], others given generic clopidogrel). We assumed patients had their index event at 65-70 years of age and had a 42.7% incidence of HPR 24-48 hours post-revascularisation. The analysis was conducted from the perspective of six countries (France, Germany, Italy, Spain, the Netherlands and United Kingdom) and used a one-year cycle length. Event data for P2Y12 inhibitors were taken from multinational randomised trials and adjusted using country-specific epidemiologic data. Neither universal ticagrelor nor prasugrel were found to be cost-effective (all ICERs >40,250€ or £36,600/QALY) compared to their corresponding PRA-driven strategies in any of the countries evaluated. Results were sensitive to differences in P2Y12 Inhibitors costs and drug-specific relative risks of major adverse cardiac events. Monte Carlo simulation suggested universal ticagrelor or prasugrel were cost-effective in only 25-44% and 11-17% of 10,000 iterations compared to their respective PRA-driven strategies, when applying a willingness-to-pay threshold = €30,000 or £20,000/QALY. In conclusion, the universal use of newer P2Y12 inhibitors is not likely cost-effective compared to PRA-driven strategies.

Timing of recurrent venous thromboembolism early after the index event: a meta-analysis of randomized controlled trials.

INTRODUCTION: Studies suggest a decreasing risk of recurrent venous thromboembolism (rVTE) in relation to time since the index event. We sought to conduct a meta-analysis examining the time course of rVTE over the first 3-months of anticoagulation. MATERIALS AND METHODS: A literature search of MEDLINE, EMBASE and CENTRAL (through 4/2013) was conducted to identify randomized trials of acute pharmacologic treatment and prevention of rVTE, enrolling ≥200 subjects/treatment arm, requiring anticoagulation for ≥3-months and reporting time-to-objectively-confirmed rVTE. Trials assessing extended-duration treatment, randomizing only cancer patients or not in English were excluded. Treatment arms were divided into monthly and weekly time periods for comparison (months 1-3 and weeks 1-12 after the index event). Treatment arm rVTE rates (per person-year) were pooled using a random-effects approach. RESULTS: Fifteen trials (31 treatment arms; n=27,237) were included. Higher rVTE rates were observed during the first month after the index event (0.19, 95% CI=0.16-0.23) compared to the second (0.05, 95% CI 0.04-0.06; p<0.001 vs. first month) and third months (0.02, 95% CI=0.02-0.03; p<0.001 vs. first month). While the highest rate of rVTE was in week 1 (0.29, 95% CI=0.21-0.37; p<0.01 vs. week 2), rates remained high through the fourth week (between 0.15 and 0.10 events/person-year) before decreasing and stabilizing at week 5 (≤0.05 events/person-year; p<0.01 vs. week 4). CONCLUSIONS: Our findings demonstrate a significant interaction between rVTE rates and time after the index event. High rVTE rates during the 3-4 weeks following the index event emphasize the importance of frequent surveillance during this time and the early optimization of pharmacologic therapy.