Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 4-year follow-up and analysis of relative progression-free survival from the randomized ELOQUENT-2 trial.

BACKGROUND: The randomized phase 3 ELOQUENT-2 study (NCT01239797) evaluated the efficacy and safety of elotuzumab plus lenalidomide and dexamethasone (ELd) versus lenalidomide and dexamethasone (Ld) in relapsed/refractory multiple myeloma (RRMM), and to date, has the longest follow-up of any monoclonal antibody in patients with RRMM. METHODS: In this extended 4-year follow-up of the ELOQUENT-2 trial, the coprimary endpoints of progression-free survival (PFS) and overall response rate as well as the secondary endpoint of overall survival were assessed. In the absence of head-to-head trials comparing Ld-based triplet regimens to guide treatment selection, 4 randomized controlled trials-ELOQUENT-2, ASPIRE, TOURMALINE-MM1, and POLLUX-were indirectly compared to provide insight into the relative efficacy of these regimens in RRMM. RESULTS: Data at 4 years were consistent with 2- and 3-year follow-up data: ELd reduced the risk of disease progression/death by 29% versus Ld (hazard ratio, 0.71) while maintaining safety. The greatest PFS benefit among the assessed subgroups was observed in patients at the median time or further from diagnosis (≥3.5 years) with 1 prior line of therapy, who had a 44% reduction in the risk of progression/death, and in patients in the high-risk category, who had a 36% reduction in favor of ELd. This regimen also showed a relative PFS benefit that was maintained beyond 50 months. CONCLUSIONS: The sustained PFS benefit and long-term safety of ELd at 4 years, similar to those observed at 2 and 3 years, support ELd as a valuable therapeutic option for the long-term treatment of patients with RRMM.

Estimation of the impact of warfarin's time-in-therapeutic range on stroke and major bleeding rates and its influence on the medical cost avoidance associated with novel oral anticoagulant use-learnings from ARISTOTLE, ROCKET-AF, and RE-LY trials.

Warfarin's time-in-therapeutic range (TTR) is highly variable among patients with nonvalvular atrial fibrillation (NVAF). The objective of this study was to estimate the impact of variations in wafarin's TTR on rates of stroke/systemic embolism (SSE) and major bleedings among NVAF patients in the ARISTOTLE, ROCKET-AF, and RE-LY trials. Additionally, differences in medical costs for clinical endpoints when novel oral anticoagulants (NOACs) were used instead of warfarin at different TTR values were estimated. Quartile ranges of TTR values and corresponding event rates (%/patient - year = %/py) of SSE and major bleedings among NVAF patients treated with warfarin were estimated from published literature and FDA documents. The associations of SSE and major bleeding rates with TTR values were evaluated by regression analysis and then the calculated regression coefficients were used in analysis of medical cost differences associated with use of each NOAC versus warfarin (2010 costs; US payer perspective) at different TTRs. Each 10 % increase in warfarin's TTR correlated with a -0.32%/py decrease in SSE rate (R(2) = 0.61; p < 0.001). Although, the rate of major bleedings decreased as TTR increased, it was not significant (-0.035%/py, p = 0.63). As warfarin's TTR increased from 30 to 90% the estimated medical cost decreased from -$902 to -$83 for apixaban, from -$506 to +$314 for rivaroxaban, and from -$596 to +$223 for dabigatran. Among NVAF patients there is a significant negative correlation between warfarin's TTR and SSE rate, but not major bleedings. The variations in warfarin's TTR impacted the economic comparison of use of individual NOACs versus warfarin.

Realized and Projected Cost-Savings from the Introduction of Generic Imatinib Through Formulary Management in Patients with Chronic Myelogenous Leukemia.

BACKGROUND: Imatinib, a first-generation tyrosine kinase inhibitor (TKI), and the newer second-generation TKIs have dramatically improved outcomes for patients with chronic myelogenous leukemia (CML). A previous model estimated the potential cost-savings over the next 2 years after the loss of patent exclusivity for imatinib in the United States in 2016 and its availability in a generic form. Payers have indeed realized meaningful savings, but it took 2 years for the prices of generic imatinib to decline substantially. OBJECTIVE: To quantify the cost-savings for a US health plan from the passive substitution of generic imatinib and the impact of step-edit therapy with the use of generic imatinib before coverage of a second-generation TKI. METHODS: We updated the previously published model utilizing hypothetical 1-million-member commercial and Medicare plans to include current TKI use and pricing combined with recent epidemiologic data. Regression models were used to project utilization to 5 years after the loss of imatinib's patent exclusivity. We compared generic imatinib costs with a scenario in which generic imatinib was not available. The impact of a step-edit therapy restriction was explored for patients with incident CML. The analyses were repeated for the entire US population based on national census data. RESULTS: The 1-million-member commercial plan saved $0.5 million (3%) from pharmacy spending on TKIs in year 1 and $3.9 million (19%) in year 2 after the loss of patent exclusivity. The projected savings significantly increased to $7.8 million (37%), $8.3 million (39%), and $8.6 million (40%) in years 3, 4, and 5, respectively. Step-edits strategies were projected to result in small incremental savings of $0.3 million (1.5%) annually in years 3 to 5. The 1-million-member Medicare plan saved $1.7 million (3%) in year 1 and $14.1 million (19%) in year 2. The projected savings were $27.8 million (37%), $29.5 million (39%), and $30.8 million (40%), with step-edit estimated to add only $0.9 million (1.2%) annually in years 3 to 5. Generic imatinib saved US payers $2.5 billion (13% of the total spending on TKIs) in years 1 and 2. In years 3 to 5, the cumulative projected savings totaled $12.2 billion, and the savings were expected to grow to 39% as a result of passive generic imatinib substitution, with only 1.7% additional savings from step-edit restriction. CONCLUSIONS: As a result of a lower price for generic imatinib relative to the brand-name version of the drug, substantial cost-savings to US payers over the next 3 years are expected without step-edit formulary management restrictions. Cost-saving strategies, including formulary management restrictions, should adhere to evidence-based guidelines to ensure the appropriate use of generic imatinib and all available TKIs, with the objective to maintain positive outcomes and, in turn, increase the value of patient care.

Economic modeling to evaluate the impact of chronic myeloid leukemia therapy management on the oncology care model in the US.

Objective: To develop an economic model to evaluate changes in healthcare costs driven by restricting usage of branded tyrosine kinase inhibitors (TKIs) through substitution with generic imatinib among chronic myeloid leukemia (CML) patients in a typical Oncology Care Model (OCM) practice, and examine the impact on Performance-Based Payment (PBP) eligibility. Methods: An Excel-based economic model of an OCM practice with 1,000 cancer patients during a 6-month episode of care was developed. Cancer types and proportions of patients treated in the practice were estimated from an OCM report. All-cause healthcare costs were obtained from published literature. It was assumed that if a practice restricts usage of branded TKIs for newly-diagnosed CML patients, 80% of the market share of branded imatinib and 50% of the market shares of 2nd-gen TKIs would shift to generic imatinib. Among established TKI-treated patients, it was assumed that 80% of the market share of branded imatinib and no patients treated with 2nd-gen TKIs would shift to the generic. Results: Four CML patients were estimated for a 1,000-cancer patient OCM practice with a total baseline healthcare cost of $51,345,812 during a 6-month episode. If the practice restricts usage of branded TKIs, the shift from 2nd-gen TKIs to generic imatinib would reduce costs by $12,970, while shifting from branded to generic imatinib lowers costs by $25,250 during a 6-month episode. Minimum reductions of $3,013,832 in a one-sided risk model and $2,372,010 in a two-sided risk model are required for PBP eligibility; the shift from 2nd-gen TKIs to generic imatinib would account for 0.4% and 0.5% of the savings required for a PBP, respectively. Conclusions: This analysis indicates that the potential cost reduction associated with restricting branded TKI usage among CML patients in an OCM setting will represent only a small proportion of the cost reduction needed for PBP eligibility.

Impact of earlier versus later monitoring on disease progression and healthcare costs among patients with chronic myeloid leukemia in the United States.

We evaluated the impact of molecular monitoring earlier as compared to later in the course of chronic myeloid leukemia (CML) on disease progression and healthcare costs in the real-world setting in the US. Patients with a diagnosis of CML were identified from the MarketScan claims databases (1 January 2006 to 30 June 2016). Multivariable regression analyses were used to control for differences in patient cohorts with earlier versus later monitoring. Of the 2730 CML patients in the study population, 60% (n = 1633) received earlier monitoring and 40% (n = 1097) received later monitoring only. After adjusting for differences in patient characteristics, patients with earlier monitoring had a lower likelihood of CML progression during the follow-up period (odds ratio: 0.72, confidence interval: 0.53-0.96; p = .03) and lower total healthcare costs ($6794 versus $9782 per-patient-per-month, p < .001) than patients with later monitoring. Patients who are monitored earlier in the course of CML may have better outcomes and lower total costs of care.

Impact of Genetic Mutations and Health Plan Access to Therapies on Treatment Response and Drug Costs Related to Tyrosine Kinase Inhibitor Treatment Among Patients With Chronic Myelogenous Leukemia.

OBJECTIVES: This study assessed treatment responses and economic consequences of limiting access to the second-generation BCR-ABL1 tyrosine kinase inhibitors (2G-TKI), dasatinib and nilotinib, for treatment of chronic myelogenous leukemia, while taking into account frequencies of genetic mutations that exhibit different sensitivities to the 2G-TKIs. METHODS: Frequencies of BCR-ABL1 mutations and the impact of mutations on responses to 2G-TKIs were obtained from published literature and used as inputs in a decision analytics model. Complete hematologic response (CHR) and major cytogenetic response (MCyR) were estimated after 12 months of 2G-TKI treatment. Total annual 2G-TKI drug costs per CHR and MCyR were estimated and compared among 3 2G-TKI access scenarios: (1) open access to both 2G-TKIs; (2) access restricted to dasatinib (DASA-only); and (3) access restricted to nilotinib (NILO-only). RESULTS: Among a hypothetical cohort of 1000 2G-TKI-treated chronic myelogenous leukemia patients, the percentage of patients with CHR and MCyR were greatest for the open access plan (CHR: 93%, MCyR: 56%), followed by DASA-only (88%, 53%) and NILO-only (67%, 47%). Compared with the 2G-TKI costs per CHR in open access ($120,706/CHR), the costs were 5% higher ($126,753/CHR) in DASA-only and 41% higher ($169,990/CHR) in NILO-only. Likewise, compared with the 2G-TKI costs per MCyR in open access ($198,284/MCyR), the costs were 6% higher ($209,259/MCyR) in DASA-only and 22% higher ($241,515/MCyR) in NILO-only. CONCLUSION: Open access to both 2G-TKIs is associated with improved clinical and economic outcomes: greater treatment response rates (CHR and MCyR) and lower drug costs compared with restricted access to 2G-TKIs.

Incidence of type 2 diabetes mellitus and hyperlipidemia in patients prescribed dasatinib or nilotinib as first- or second-line therapy for chronic myelogenous leukemia in the US.

OBJECTIVE: Evaluate the incidence of type 2 diabetes mellitus (T2DM) and hyperlipidemia (HLD) in CML patients initiating therapy with dasatinib or nilotinib. METHODS: Retrospective study using MarketScan claims from January 2006 to December 2014. The first analysis evaluated occurrence of T2DM, defined as ≥2 claims with a T2DM ICD-9 code or 1 diagnosis claim and an antidiabetic medication. The second analysis evaluated occurrence of HLD, defined as ≥2 claims with an HLD ICD-9 code, or 1 diagnosis claim and an anti-HLD medication. Incidence rates were computed as number of events divided by sum of person years (PY) at risk for all subjects. Multivariate Cox proportional hazards models estimated hazard ratios (HRs) for T2DM or HLD. RESULTS: There were 2004 and 1280 patients who met the criteria for the T2DM analysis (n = 1272 dasatinib, n = 732 nilotinib) and HLD analysis (n = 845 dasatinib, n = 435 nilotinib). The incidence rate of T2DM was 40.4 per 1000 PY (95% CI: 27.60, 56.98) for nilotinib and 17.6 per 1000 PY (95% CI: 11.14, 26.38) for dasatinib. HR for occurrence of T2DM was 2.77 (95% CI: 1.58, 4.86), indicating that patients on nilotinib had a significantly higher adjusted risk for incident T2DM. The incidence rate of HLD was 74.6 per 1000 PY (95% CI: 50.70, 105.94) for nilotinib and 46.4 per 1000 PY (95% CI: 33.00, 63.45) for dasatinib. HR for occurrence of HLD was 1.75 (95% CI: 1.07, 2.87) indicating that patients on nilotinib had a significantly higher adjusted risk for incident HLD. CONCLUSIONS: Patients receiving nilotinib had significantly higher rates of incident T2DM or HLD than patients on dasatinib.

Economic value of regular monitoring of response to treatment among US patients with chronic myeloid leukemia based on an economic model.

BACKGROUND: Regular molecular monitoring with reverse-transcription quantitative PCR (RT-qPCR) analysis of BCR-ABL1 transcripts is associated with reduced disease progression among patients with chronic myeloid leukemia (CML). Molecular monitoring assists in the timely detection of primary or secondary resistance to tyrosine kinase inhibitor (TKI) therapy and is a recommended practice by the National Comprehensive Cancer Network guidelines. An economic model was developed to estimate the potential impact of CML monitoring vs lack of monitoring on patient healthcare costs. METHODS: An Excel-based decision-analytic economic model was developed from a US payer perspective. The model was used to estimate the expected healthcare cost differences between regular molecular monitoring of CML patients and lack of monitoring. CML progression rates among patients with vs without monitoring, the annual cost of CML progression, the average number of monitoring tests per year, and the average cost per RT-qPCR monitoring test were incorporated into the model. Univariate and multivariable sensitivity analyses were conducted. RESULTS: Based on estimates in published literature, disease progression to the accelerated/blast phase occurs among 0.35% of patients with monitoring and 5.12% of patients without monitoring, and the annual cost of CML progression is $136,308 per patient year. The analysis found that total healthcare costs, including the costs associated with CML progression and RT-qPCR monitoring tests (three tests per year), were $1,142 for patients with monitoring and $6,982 for patients without monitoring (difference = $5,840). In a hypothetical cohort of 100 patients with CML, achieving a 100% monitoring rate was associated with a total cost-savings of $584,005 compared to a 0% monitoring rate. This cost-savings remained consistent under both univariate and multivariable sensitivity analyses. CONCLUSION: Regular CML monitoring was associated with improved outcomes among CML patients and, consequently, reduced healthcare costs.

The value of open access and a patient centric approach to oral oncolytic utilization in the treatment of Chronic Myelogenous Leukemia: A U.S. perspective.

INTRODUCTION: Since the introduction of tyrosine kinase inhibitors (TKIs), the treatment of patients with chronic myelogenous leukemia (CML) has resulted in significant improvement in patient survival but at a higher pharmaceutical cost to payers. The recent introduction of generic imatinib presents an opportunity to lower pharmacy costs within a population that is growing due to improved survival. Recent literature has focused on the likely benefits to payers of step therapy through generic imatinib. Areas covered: This review provides a perspective that is broader than the evaluation of financial savings or narrowly defined health economic metrics by incorporating factors such as CML patient heterogeneity, including varying levels of disease progression risk, comorbidities and genetic mutation status, differences in TKI product profiles, clinical guideline recommendations, and the importance of individualized patient care. A focused literature review evaluating the real-world impact of utilization management programs is presented. Expert commentary: The findings indicate that payers can achieve substantial savings without the need to implement utilization management policies. Compromises in the ability to provide individualized patient care and unwanted economic consequences resulting from increased costs of disease progression, adverse events, and lack of response to treatment due to utilization management are summarized.

Healthcare and economic burden of adverse events among patients with chronic myelogenous leukemia treated with BCR-ABL1 tyrosine kinase inhibitors.

OBJECTIVES: BCR-ABL1 tyrosine kinase inhibitors (TKIs) are established treatments for chronic myelogenous leukemia (CML); however, they are associated with infrequent, but clinically serious adverse events (AEs). The objective of this analysis was to assess healthcare resource utilization and costs associated with AEs, previously identified using the FDA Adverse Event Reporting System (FAERS) in another study, among TKI-treated patients. METHODS: Adult patients with ≥1 inpatient or ≥2 outpatient ICD-9-CM diagnosis codes for CML and ≥1 claim for a TKI treatment between January 1, 2006 and September 30, 2012 were identified from the Commercial and Medicare MarketScan databases. The first claim for a TKI was designated as the index event. Patients were required to have no TKI treatment during a 12-month baseline period. Healthcare resource utilization and costs associated with select AEs having the strongest association with TKI treatment (femoral arterial stenosis [FAS], peripheral arterial occlusive disease [PAOD], intermittent claudication, coronary artery stenosis [CAS], pericardial effusion, pleural effusion, malignant pleural effusion, conjunctival hemorrhage) were evaluated during a 12-month follow-up period. RESULTS: The study sample included 2,005 CML patients receiving TKI therapy (mean age = 56 years; 56% male). Among all evaluated AEs, the highest mean inpatient healthcare costs were observed for FAS ($16,800 per patient) and PAOD ($14,263 per patient), which had total mean medical costs (inpatient + outpatient) of $17,015 and $15,154 per patient, respectively. Mean outpatient healthcare costs were highest for CAS ($1,861 per patient), followed by intermittent claudication ($947 per patient), PAOD ($891 per patient), and pleural effusion ($890 per patient). Total mean medical costs for fluid retention-related AEs, including pericardial effusion and pleural effusion, were $2,797 and $1,908 per patient, respectively. CONCLUSIONS: The healthcare costs of AEs identified in the FAERS as having the strongest association with TKI treatment are substantial. Vascular stenosis-related AEs, including FAS and PAOD, have the highest cost burden.

Using Health Care Claims Data to Assess the Prevalence of Hodgkin Lymphoma and Relapsed or Refractory Hodgkin Lymphoma in the United States.

PURPOSE: Although most patients with Hodgkin lymphoma (HL) respond to primary therapy, some patients experience relapses or are refractory to treatment (RR-HL). The objectives of this study were to investigate the prevalence of HL and RR-HL in the United States by using a large health care claims database. METHODS: Patients with ≥1 diagnosis for HL between January 1, 2013, and September 30, 2014 (prevalence assessment period), in the MarketScan Commercial and Medicare databases were identified. RR-HL patients were identified as any HL patient with any record for either an autologous stem cell transplantation (ASCT) or brentuximab vedotin (BV) treatment between January 1, 2010, and September 30, 2014 (entire study period). Prevalence rates of HL and RR-HL were calculated as the number of patients with HL or RR-HL divided by the total number of persons with insurance enrollment during the prevalence assessment period (January 1, 2013-September 30, 2014) in the MarketScan databases. Age- and sex-specific prevalence rates for HL and RR-HL were estimated. The estimated prevalence rates based on the claims database analysis were applied to the US national population estimates from the US Census Bureau to project the national prevalence of HL and RR-HL in the United States. FINDINGS: Of persons with any insurance enrollment in the MarketScan databases during the prevalence assessment period (N = 58,968,235), 24,812 (0.04%) were identified as having HL (mean age, 48.6 years) between January 1, 2013, and September 30, 2014. Of this HL population, 712 (2.87%) were identified as RR-HL patients, with 432 (1.74%) having received ASCT, 199 (0.80%) having received BV, and 81 (0.33%) having received both ASCT and BV treatments during the study period. According to the national projection according to the US Census population estimate, the overall number of persons with HL in the United States was estimated at 149,615 (469.2 per 1 million) in 2014, with 2.72% (N = 4077; 12.8 per 1 million) having RR-HL. IMPLICATIONS: Among patients in the United States with HL, the proportion of RR-HL patients during the study period was estimated at <3% of the HL population.

Evaluation of healthcare resource utilization and incremental economic burden of patients with chronic myeloid leukemia after disease progression to blast phase.

AIMS: To evaluate healthcare resource utilization and economic burden of patients with chronic myeloid leukemia (CML) progression to the blast phase. METHODS: Patients (≥ 18 years) with ≥1 inpatient or ≥2 outpatient CML diagnoses were identified from the MarketScan Commercial and Medicare databases (January 1, 2007-June 30, 2015). CML patients were grouped into two study cohorts, those with evidence of disease progression to the blast phase and those without. Patients were required to have continuous medical and prescription coverage during a 12-month baseline period, in which demographics and clinical characteristics were evaluated. All-cause healthcare resource utilization and costs were evaluated during the baseline period, and a variable follow-up period, lasting ≥1 day and up to 1 year. Generalized linear models (GLM) were used to compare the incremental costs of CML patients with vs without progression. RESULTS: Of the overall study population, 587 (7%) experienced disease progression and 7,504 (93%) did not. On the index date, of patients with progression, ∼ 31% were treated with allogeneic hematopoietic cell transplant and 69% with chemotherapy. During the baseline period, mean total healthcare costs, including costs for hospitalizations and outpatient costs, were significantly greater for CML patients with progression as compared to those without progression ($143,778 vs $53,143, p < .001). During the follow-up, mean total healthcare costs, costs for hospitalizations, and outpatient medical service costs were substantially greater for patients with progression as compared to those without progression; however, costs for outpatient prescriptions were less for patients who progressed. When patient characteristics were controlled for, mean incremental 1-year cost for CML patients with vs without progression was $270,925 (confidence interval = $235,290-$311,958, p < .001). CONCLUSIONS: The healthcare burden, in terms of healthcare resource utilization and costs, of patients with CML progression is substantial. Healthcare providers and payers should consider various strategies to minimize the rate of CML progression.

Elevated Cardiovascular Disease Risk in Patients With Chronic Myelogenous Leukemia Seen in Community-based Oncology Practices in the United States.

INTRODUCTION: Current National Comprehensive Cancer Network guidelines recommend that comorbidities, including cardiovascular disease (CVD), be considered when selecting tyrosine kinase inhibitors for the treatment of chronic myelogenous leukemia (CML). We report here the prevalence of CVD and its risk factors in patients with CML treated by community-based United States (US) oncologists. PATIENTS AND METHODS: Adult patients with a confirmed diagnosis of CML and ≥ 1 encounter after the first date of CML diagnosis in an electronic medical record database between January 1, 2005 and October 31, 2014 were enrolled. CVD conditions/risk factors were assessed at baseline and during the 5-year follow-up period using International Classification of Diseases, 9th Revision, Clinical Modification diagnoses codes and information from physician progress notes. One-year prevalence estimates were age- and gender-standardized for comparison to annual rates in the US population. RESULTS: A total of 1639 patients were included. At 5-year follow-up, the prevalence of CVD conditions and CVD risk factors was 33.0% and 77.7%, respectively. Compared with the general US adult population, the standardized prevalence rates at 1 year in patients with CML were significantly higher by factors of 1.3 to 3.5 times for CVD conditions, and 20% to 40% significantly higher for hypertension, diabetes, and obesity (P < .001). The prevalence of cardiovascular risk factors was not significantly higher in patients residing in the US Stroke Belt. CONCLUSION: The increased risk of CVD observed in this real-world analysis of patients with CML underscores the importance of current National Comprehensive Cancer Network recommendations to consider cardiovascular risk when selecting tyrosine kinase inhibitors.

Cost-effectiveness analysis of second-line tyrosine kinase inhibitor treatment for chronic myelogenous leukemia.

AIM: A cost-effectiveness analysis was performed for sequential treatments of chronic myelogenous leukemia (CML) with tyrosine kinase inhibitors (TKIs) after failure of 1st line imatinib, from a commercial payer perspective in the US. METHODS: A Markov model was developed to simulate lifetime treatment costs and health outcomes for TKI sequences for treatment of patients resistant or intolerant to 1st-line imatinib. Five health states were included, chronic phase 2nd-line TKI, chronic phase 3rd-line TKI, chronic phase post-TKI, advanced phases, and death. Efficacy (response achievement, loss of response, transformation, death) and safety (adverse events incidence, discontinuation) data are based on clinical trials. Resource utilization, costs, and utilities were based on product labels and publically available data. Uncertainty analyses were conducted for key inputs. RESULTS: In patients failing imatinib, dasatinib-initiating treatment sequences provide the most survival (ΔLYs = 0.2-2.0), QALYs (ΔQALYs = 0.2-1.9), and accrue highest CML-related costs (ΔCosts = $64,000-$222,000). The average ICER per QALY for dasatinib- vs imatinib-initiating sequences is $100,000 for an imatinib-resistant population. The average ICER per QALY for dasatinib- vs nilotinib-initiating sequences is $170,000 for an imatinib-resistant population, and $160,000 for an imatinib-intolerant population. CONCLUSIONS: This analysis suggests that dasatinib is associated with increased survival and quality of life compared to high dose imatinib and to a smaller extent with nilotinib, among patients resistant or intolerant to 1st-line imatinib, primarily based on higher cytogenetic response rates observed in clinical studies of dasatinib. Head-to-head studies of sequential use of dasatinib and nilotinib are needed to validate the model findings of improved survival (LYs) with better quality-of-life (QALYs) for patients initiating dasatinib in 2nd-line. However, the model findings (in light of higher cytogenetic response rates with dasatinib) are supported by other studies showing improved quality-of-life for responders, and improved survival for patients achieving cytogenetic response.

Use of Chronic Medications Among Patients with Non-Valvular Atrial Fibrillation.

BACKGROUND: Frequency of administration (once daily versus more than once daily) is believed to be an important consideration affecting drug choice. OBJECTIVE: The aim of this study was to describe the characteristics of patients with non-valvular atrial fibrillation (NVAF) and the extent to which they take chronic medications, other than anticoagulants, more frequently than once daily. METHODS: Using data from a large, national database of health insurance claims, patients with a diagnosis of NVAF between 1 July 2008 and 30 September 2011 were identified, along with their prescription medications, to determine the proportion of patients taking chronic medications more than once a day. Prescription medications, co-morbidities, and CHADS2 and CHA2DS2-VASc scores were evaluated. CHADS2 assesses the risk of stroke in NVAF patients with the following risk factors: Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, and history of prior Stroke or transient ischemic attack. The CHA2DS2-VASc score adds the following risk factors to the CHADS2 score: Age 65-74 years, Vascular Disease, and Sex Category (Female). RESULTS: Overall, 324,172 patients with NVAF with mean CHADS2 and CHA2DS2-VASc scores of 1.51 and 3.08, respectively, were included in the study. Of these patients, 299,716 (92.5 %) took chronic medications, with an average of 6.9 medications per patient, and 215,527 (66.5 % of all patients or 71.9 % of those taking chronic medications) took medications more than once per day. CONCLUSION: Use of chronic medications other than anticoagulants is common among patients with NVAF, and medications are typically taken multiple times per day. The average number of medications per patient and multiple therapeutic classes prescribed underscore the clinical complexity of NVAF patients. Hence, the choice of a once daily anticoagulant versus a more than once daily anticoagulant may be less relevant in a real world NVAF population in terms of a potential convenience benefit.

Anticipated Impact of Generic Imatinib Market Entry on the Costs of Tyrosine Kinase Inhibitors.

BACKGROUND: Imatinib was the first BCR-ABL tyrosine kinase inhibitor (TKI) approved in the United States for the treatment of patients with chronic myelogenous leukemia and is currently the most prescribed TKI. The impending loss of patent exclusivity for imatinib has the potential to reduce costs for payers. OBJECTIVE: The primary objectives of this study were to estimate the economic impact of the loss of patent exclusivity for branded imatinib and to calculate the relative impact of requiring prior authorization (PA) for the use of generic imatinib before a branded TKI. The secondary objective was to evaluate the potential relative cost impact of using a preferred branded TKI in addition to the PA requirement for generic imatinib before a branded TKI. METHODS: A Microsoft Excel-based model was developed from the perspective of a US payer (commercial and Medicare) for a 2-year period. Data on utilization, patient out-of-pocket cost, and market share were obtained from an analysis of Truven Health MarketScan claims. It was assumed that the cost of generic imatinib would be 47.8% of the price of branded imatinib. It was assumed that 70% of patients receiving branded imatinib would shift to generic imatinib in year 1, and 95% would shift in year 2 after loss of patent exclusivity. Formulary management could be applied through PA requiring the use of generic imatinib before a branded TKI for patients newly prescribed TKI therapy. It was assumed that 74% of PA requests would be approved, and that the administrative cost of each would be $20. RESULTS: In a hypothetical 1 million member commercial plan, the loss of patent exclusivity for branded imatinib produced cost-savings of $6.8 million during 2 years, or 28.8% of the total pharmacy spending on the TKI class. The savings were even greater in a 1 million member Medicare plan, at $22.9 million (28.8%). Formulary management reduced incremental TKI spending by 1.1% and 2.2% for the commercial and Medicare plans, respectively. CONCLUSIONS: In the absence of formulary management beyond generic substitution, the loss of patent exclusivity for branded imatinib is expected to reduce total pharmacy spending on TKIs by nearly 33% during 2 years. Given the small number of newly treated patients, formulary management of the TKI class through restricted access to branded imatinib, with or without a preferred branded TKI, has limited potential for incremental cost-savings.

Use of Real-World Claim Databases to Assess Prevalence of Comorbid Conditions Relevant to the Treatment of Chronic Myelogenous Leukemia Based on National Comprehensive Network Treatment Guidelines.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines state that based on toxicity profiles, 1 second-generation tyrosine kinase inhibitor (TKI) indicated for first-line therapy (ie, dasatinib, nilotinib) may be preferred over the other for treatment of chronic myelogenous leukemia (CML) patients with certain comorbidities. This study assessed the prevalence of comorbid conditions relevant to TKI treatment choice among CML patients in the US real-world setting. PATIENTS AND METHODS: Patients who had CML and initiated TKI treatment were identified from the MarketScan Commercial and Medicare databases (January 1, 2006, to June 30, 2013). Demographics and prevalence of comorbid conditions relevant to TKI treatment choice per NCCN guidelines (heart disease, arrhythmia, diabetes, pancreatitis, pleural effusion, lung disease) were assessed among the overall study population and among subgroups. RESULTS: The median age of the CML study population newly initiated on TKI treatment (ie, imatinib, dasatinib, or nilotinib; n = 2296) was 56 years. Approximately 41% of the CML study population had at least 1 comorbid condition that may influence the choice of TKI treatment as recommended by NCCN guidelines. The most prevalent comorbid condition was heart disease (23%), followed by diabetes (18%) and lung disease (13%). The prevalence of comorbid conditions relevant to TKI treatment choice varied among patients of different age groups, gender, and US regions. CONCLUSION: The results of this analysis provide real-world evidence that the prevalence of relevant comorbid conditions is substantial among CML patients in the US managed care setting and therefore needs to be considered throughout various health care decision-making processes related to CML.

Comparison of Medical Costs of Patients With Atrial Fibrillation Unsuitable for Warfarin Treatment With Apixaban or Aspirin Based on AVERROES Trial.

BACKGROUND: The AVERROES trial name is the following: The Apixaban Versus Acetylsalicylic Acid (ASA) to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial demonstrated that apixaban reduced the risk of stroke relative to aspirin, without significantly increasing major bleeding risk in patients with atrial fibrillation (AF) considered unsuitable for warfarin therapy. Based on AVERROES trial results, this study compared the medical costs for clinical end points among patients with AF treated with either apixaban or aspirin. METHODS: Medical costs per patient-year for clinical events were determined. Based on clinical event rates for patients in the AVERROES trial, medical costs excluding drug costs were estimated for apixaban- and aspirin-treated patient groups. RESULTS AND CONCLUSIONS: Based on AVERROES trial results, among patients with AF unsuitable for warfarin therapy, apixaban use was estimated to be associated with a mean medical cost avoidance of US$735 in a patient-year relative to aspirin. The primary driver was the significant reduction in ischemic stroke rate. The medical cost reduction associated with apixaban use was consistent in sensitivity analyses.

Reviewing a clinical decision aid for the selection of anticoagulation treatment in patients with nonvalvular atrial fibrillation: applications in a US managed care health plan database.

PURPOSE: The Clinical Decision Aid was created to assist in selecting anticoagulant therapies for patients with nonvalvular atrial fibrillation. The aid incorporates a patient's absolute risk for stroke and bleeding, relative stroke risk reduction, and increase in relative bleeding risk to identify the agent with the lowest net risk. We describe theoretical implications of utilizing the aid at a US managed care population level. METHODS: This retrospective study used claims data from a large US managed care database including enrollees in commercial and Medicare Advantage plans. The distribution of patients across each possible combination of scores on the HAS-BLED scale (evidence of hypertension, abnormal renal or liver function, stroke, bleeding, labile INR, age >65 years, and drugs or alcohol abuse or dependence) and the CHA2DS2-VASc scale (CHADS2 [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism] with additional nonmajor stroke risk factors, including age 65-74 years, female sex, and vascular disease) was generated. We assessed the correlation between the HAS-BLED and CHA2DS2-VASc scores and derived the optimal treatment options based on various bleeding ratios. FINDINGS: Data from 48,260 patients were included in the analysis. The MAPD subset had a higher mean HAS-BLED score (2.17 vs 1.39; P < 0.001) and a higher mean CHA2DS2-VASc score (3.35 vs 2.05; P < 0.001) than did the commercial subset. Pearson coefficients suggested a moderate to strong positive correlation between the HAS-BLED and CHA2DS2-VASc scores among the commercial (0.730; P < 0.001) and MAPD (0.568; P < 0.001) enrollees. Based on a 2:1 bleeding-to-stroke risk ratio, 70.50% of patients would be recommended treatment with apixaban; 25.86%, no treatment; 3.62%, acetylsalicylic acid; and 0.01%, dabigatran 150 mg, if the Clinical Decision Aid were to be used for anticoagulant treatment selection. IMPLICATIONS: Evidence-based clinical decision-making tools utilizing risk assessment for recommending a treatment may be valuable for not only health care providers but also health care payers in optimizing care at the population level.

Health care burden of dyspepsia among nonvalvular atrial fibrillation patients.

BACKGROUND: Although dyspepsia is common among nonvalvular atrial fibrillation (NVAF) patients, its impact on patient health and cost has not been adequately studied. OBJECTIVE: To evaluate the incremental health care burden associated with dyspepsia among NVAF patients and its impact on warfarin treatment. METHODS: NVAF patients ≥ 18 years of age with continuous insurance coverage were identified (January 1, 2007, to December 31, 2009) from the MarketScan Commercial and Medicare Research databases. Patients with 1 inpatient or 2 outpatient dyspepsia diagnoses within 12 months following any NVAF diagnosis were grouped into the dyspeptic cohort, and patients without any dyspepsia diagnosis were grouped into the nondyspeptic cohort. Of the overall cohorts, patients were matched by key patient characteristics. Dyspepsia was further categorized as having a prior history of dyspepsia (chronic) or no dyspepsia (nonchronic) during the baseline period. Health care resource utilization, associated costs, and warfarin use were evaluated during a 12-month follow-up period. RESULTS: Of NVAF patients included in the study (N = 142,322), 10.4% were diagnosed with dyspepsia. After matching for key characteristics, NVAF patients with dyspepsia had significantly greater inpatient, outpatient, and prescription claims per patient year than those without dyspepsia (1.24 ± 1.21 vs. 0.36 ± 0.68, P < 0.0001; 110.18 ± 101.03 vs. 66.98 ± 72.43, P < 0.0001; and 52.13 ± 35.30 vs. 44.29 ± 32.41, P < 0.0001, respectively). This greater number of claims was reflected in higher annual inpatient, outpatient, and prescription payments ($23,610 ± $54,748 vs. $5,509 ± $19,142, P < 0.0001; $18,182 ± $28,790 vs. $9,765 ± $22,009, P < 0.0001; and $4,661 ± $5,628 vs. $3,897 ± $4,586, P < 0.0001, respectively). NVAF patients with chronic dyspepsia were the least likely to take warfarin for stroke prevention. CONCLUSIONS: NVAF patients with dyspepsia experienced more all-cause hospitalizations and required more outpatient medical services, all associated with greater expenditures than NVAF patients without dyspepsia. Additionally, dyspepsia may be a barrier to warfarin use among NVAF patients.