Assessment of algorithms for identifying patients with triple-class refractory multiple myeloma using real-world data.

Objective: Patients with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognoses. This high unmet need has prompted the development of new therapies allowing for improved outcomes for these patients. Recently, new targeted therapies for the treatment of patients with relapsed or refractory MM have been approved based on single-arm clinical trial results. Real-world (RW) data enable a better understanding of the effectiveness of new therapies in clinical practice and provide external controls for single-arm studies. However, using RW data to identify patients with TCR MM is challenging and subject to limitations. Methods: In this retrospective cohort study of an analysis of the COTA electronic health record (EHR) database, we used four algorithms to define refractory status and created four groups of patients with TCR MM initiating post-TCR therapy. Each algorithm relied on slightly different criteria to identify TCR patients, but all were based on the International Myeloma Working Group (IMWG)-derived and/or healthcare provider (HCP)-reported progressions within the database. Results: A total of 3815 patients with newly diagnosed MM met the eligibility criteria for this study. The choice of the algorithm did not impact the characteristics of identified patients with TCR MM (Algorithm 1 [n = 404], Algorithm 2 [n = 123], Algorithm 3 [n = 404], and Algorithm 4 [n = 375]), including their demographic and disease characteristics, MM treatment history, or treatment patterns received after becoming TCR. However, identifying TCR MM using a combination of IMWG-derived and HCP-reported progressions allowed up to a 70% increase in the size of the identified group of patients compared with using only IMWG-derived progressions. Conclusion: In RW settings, progressions from both IMWG-derived data and physician reports may be used to identify patients with TCR MM.

Medicare characteristics, treatment, cost and survival in triple class exposed relapsed or refractory multiple myeloma.

Background: This study describes real-world treatment patterns of Medicare beneficiaries with relapsed or refractory multiple myeloma (RRMM) who are triple class exposed (TCE). Materials & methods: Retrospective analysis of Medicare fee for service claims to identify a cohort age >65 with RRMM + TCE, 1 January 2016 to 30 June 2019. Outcomes: Initiation of a new treatment regimen (TCE1), healthcare resource utilization, cost and mortality. Results: Of 5395 patients with RRMM + TCE, 1672 (31.0%) initiated a new therapy (TCE1). During TCE1, 97 TCE1 drug combinations were observed and RRMM treatments were the largest cost driver. Median time to TCE1 discontinuation was 3.3 months. Few patients received subsequent treatment and 41.3% of study patients died. Conclusion: There is no clear standard-of-care for Medicare patients with RRMM + TCE and prognosis remains poor.

This research study describes outcomes in older Medicare patients with relapse or refractory multiple myeloma (RRMM) who failed three different classes of treatment (triple class exposed [TCE]) between 2016 and 2019. The authors utilized data from Medicare to follow patients who started a new treatment after TCE (this group was labeled 'TCE1'), and this article describes their cancer treatment, hospitalizations, emergency department visits, physician visits, costs of care, and length of survival. The authors identified 5395 Medicare patients with RRMM + TCE during the study period, of which 1672 (31.0%) started a new therapy and were considered TCE1. Patients were 75.6 years old, on average, when they started TCE1 treatment. The authors observed 97 different TCE1 drug combinations, and 50% of patients discontinued TCE1 treatment within 3 months. Few patients received additional treatment, and 41.3% of study patients died during the study period. More than 90% of healthcare costs were related to cancer care (rather than management of other conditions). There is no clear standard-of-care for older Medicare patients with RRMM + TCE, and prognosis remains poor.

Oral anticoagulant underutilization among elderly patients with atrial fibrillation: insights from the United States Medicare database.

BACKGROUND: Oral anticoagulants (OACs) mitigate stroke risk in patients with atrial fibrillation (AF). The study aim was to analyze prevalence and predictors of OAC underutilization. METHODS: Newly diagnosed AF patients with a CHA2DS2-VASc score ≥ 2 were identified from the US CMS Database (January 1, 2013-December 31, 2017). Patients were stratified based on having an OAC prescription versus not and the OAC prescription group was stratified by direct OAC (DOACs) versus warfarin. Multivariable logistic regression models were used to examine predictors of OAC underutilization. RESULTS: Among 1,204,507 identified AF patients, 617,611 patients (51.3%) were not prescribed an OAC during follow-up (mean: 2.4 years), and 586,896 patients (48.7%) were prescribed an OAC during this period (DOAC: 388,629 [66.2%]; warfarin: 198,267 [33.8%]). Age ≥ 85 years (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.55-0.56), female sex (OR 0.96, 95% CI 0.95-0.96), Black race (OR 0.78, 95% CI 0.77-0.79) and comorbidities such as gastrointestinal (GI; OR 0.43, 95% CI 0.41-0.44) and intracranial bleeding (OR 0.29, 95% CI 0.28-0.31) were associated with lower utilization of OACs. Furthermore, age ≥ 85 years (OR 0.92, 95% CI 0.91-0.94), Black race (OR 0.78, 95% CI 0.76-0.80), ischemic stroke (OR 0.77, 95% CI 0.75-0.80), GI bleeding (OR 0.73, 95% CI 0.68-0.77), and intracranial bleeding (OR 0.72, 95% CI 0.65-0.80) predicted lower use of DOACs versus warfarin. CONCLUSIONS: Although OAC therapy prescription is the standard of care for stroke prevention in AF patients, its overall utilization is still low among Medicare patients ≥ 65 years old, with specific patient characteristics that predict underutilization.

Effectiveness and safety of apixaban vs warfarin among venous thromboembolism patients at high-risk of bleeding.

This study evaluated effectiveness and safety of apixaban versus warfarin among venous thromboembolism patients at high-risk of bleeding (defined as having at least one of the following bleeding risk factors: ≥75 years; used antiplatelet, NSAIDs, or corticosteroids; had prior gastrointestinal bleeding or gastrointestinal-related conditions; late stage chronic kidney disease). Adult venous thromboembolism patients initiating apixaban or warfarin with ≥1 bleeding risk factor were identified from Medicare and four commercial claims databases in the United States. To balance characteristics between apixaban and warfarin patients, stabilized inverse probability treatment weighting was conducted. Cox proportional hazards models were used to estimate the risk of recurrent venous thromboembolism, major bleeding, and clinically relevant non-major bleeding. In total, 88,281 patients were identified. After inverse probability treatment weighting, the baseline patient characteristics were well-balanced between the two cohorts. Among venous thromboembolism patients at high-risk of bleeding, apixaban was associated with significantly lower risk of recurrent venous thromboembolism, major bleeding and clinically relevant non-major bleeding. No significant interactions were observed between treatment and number of risk factors on major bleeding and clinically relevant non-major bleeding or between treatment and type of bleeding risk factors on any of the outcomes. In conclusion, apixaban was associated with significantly lower risk of recurrent venous thromboembolism and bleeding among venous thromboembolism patients at high-risk of bleeding. Effects were generally consistent across subgroups of patients with different number or type of bleeding risk factors.

Contemporary clinical and economic outcomes among oral anticoagulant treated and untreated elderly patients with atrial fibrillation: Insights from the United States Medicare database.

BACKGROUND: Oral anticoagulants (OACs) mitigate the risk of stroke in atrial fibrillation (AF) patients. OBJECTIVE: Elderly AF patients who were treated with OACs (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin) were compared against AF patients who were not treated with OACs with respect to their clinical and economic outcomes. METHODS: Newly diagnosed AF patients were identified between January 2013 and December 2017 in the Medicare database. Evidence of an OAC treatment claim on or after the first AF diagnosis was used to classify patients into treatment-defined cohorts, and these cohorts were further stratified based on the initial OAC prescribed. The risks of stroke/systemic embolism (SE), major bleeding (MB), and death were analyzed using inverse probability treatment weighted time-dependent Cox regression models, and costs were compared with marginal structural models. RESULTS: The two treatment groups were composed of 1,421,187 AF patients: OAC treated (N = 583,350, 41.0% [36.4% apixaban, 4.9% dabigatran, 0.1% edoxaban, 26.7% rivaroxaban, and 31.9% warfarin patients]) and untreated (N = 837,837, 59.0%). OAC-treated patients had a lower adjusted risk of stroke/SE compared to untreated patients (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.68-0.72). Additionally patients receiving OACs had a lower adjusted risk of death (HR: 0.56; 95% CI: 0.55-0.56) and a higher risk of MB (HR: 1.57; 95% CI: 1.54-1.59) and this trend was consistent across each OAC sub-group. The OAC-treated cohort had lower adjusted total healthcare costs per patient per month ($4,381 vs $7,172; p < .0001). CONCLUSION: For the OAC-treated cohort in this elderly US population, stroke/SE and all-cause death were lower, while risk of MB was higher. Among OAC treated patients, total healthcare costs were lower than those of the untreated cohort.

Effectiveness and Safety of Apixaban Versus Warfarin Among Older Patients with Venous Thromboembolism with Different Demographics and Socioeconomic Status.

INTRODUCTION: Impact of demographics and socioeconomic status (SES) on anticoagulant treatment outcomes among patients with venous thromboembolism (VTE) is not well understood. This study evaluated risks of recurrent VTE, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among older patients with VTE initiating apixaban or warfarin stratified by demographics and SES. METHODS: Adult patients (≥ 65 years) who initiated apixaban or warfarin after a VTE event were selected from the US CMS Medicare database (September 2014-December 2017). Stabilized inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Patients were stratified by age, gender, race, and SES. For each subgroup, Cox proportional hazard models were used to evaluate if there was a significant interaction (p < 0.10) between treatment and subgroup for recurrent VTE, MB, and CRNMB. RESULTS: In total, 22,135 apixaban and 45,840 warfarin patients with VTE were included. Post-IPTW, patient characteristics were balanced between treatment cohorts. In older patients, apixaban treatment was associated with significantly lower risks of recurrent VTE (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.52-0.79), MB (HR 0.65; 95% CI 0.57-0.75), and CRNMB (HR 0.79; 95% CI 0.75-0.85) versus warfarin. When stratified by demographics and SES, higher incidence rates of recurrent VTE, MB, and CRNMB were observed for black vs white patients and patients with lower vs higher SES. Comparison of apixaban with warfarin by different demographic and SES subgroups showed generally consistent results as the overall analysis. For most subgroups, no significant interaction was observed between treatment and subgroup strata for recurrent VTE, MB, and CRNMB. CONCLUSION: Among older patients with VTE initiating apixaban or warfarin, higher rates of recurrent VTE and bleeding were observed in black patients and patients with lower SES. Apixaban had a lower risk of recurrent VTE, MB, and CRNMB compared to warfarin. Analyses of demographic and SES subgroups showed consistent findings.

Safety and effectiveness of apixaban compared with warfarin among clinically-relevant subgroups of venous thromboembolism patients in the United States Medicare population.

BACKGROUND: The AMPLIFY trial found significantly lower major bleeding (MB) and similar recurrent venous thromboembolism (VTE) risks associated with apixaban vs warfarin among patients with VTE. OBJECTIVES: To compare MB, clinically-relevant non-major (CRNM) bleeding, and recurrent VTE risks among clinically-relevant subgroups of newly diagnosed elderly patients with VTE prescribed apixaban vs warfarin. METHODS: US Medicare patients prescribed apixaban or warfarin within 30 days post-VTE encounter were identified. Propensity score matching (PSM) was used to control for patient characteristics. Cox models were used to assess MB, CRNM bleeding, and recurrent VTE. Subgroup analyses were conducted for index VTE encounter type, index VTE diagnosis type, index VTE etiology, sex, and frailty. RESULTS: Post-PSM, 11,363 matched pairs of patients prescribed apixaban or warfarin were identified. Apixaban had lower MB (Hazard Ratio [HR]:0.76; 95% CI:0.64-0.91) and similar recurrent VTE risks (HR:1.04; 95% CI:0.75-1.43) vs warfarin. No significant interactions were observed between treatment and index VTE encounter type, index VTE diagnosis type, or sex for risk of MB, CRNM bleeding, or recurrent VTE. Significant interactions: frail patients prescribed apixaban had a 15% lower, while non-frail patients prescribed apixaban had 32% lower CRNM bleeding risk vs those prescribed warfarin. Patients with provoked VTE prescribed apixaban trended toward a higher, while those with unprovoked VTE trended toward a lower risk of recurrent VTE vs patients prescribed warfarin. CONCLUSIONS: Apixaban was associated with significantly lower risks of MB and CRNM bleeding, and similar risk of recurrent VTE as compared with warfarin across the overall population and most subgroups.

Clinical characteristics and treatment patterns of patients with venous thromboembolism (VTE) transitioning from hospital to post-discharge settings.

OBJECTIVE: This study examined anticoagulant use during and after a hospital encounter for venous thromboembolism (VTE), a transition of care largely uncharacterized in the literature. METHODS: Adults with a VTE diagnosis code during a hospital encounter (emergency department [ED], observation area [OBS], or inpatient hospital [IP]) from January 2012 to August 2017 were identified in an electronic health records database. The first such hospital encounter was defined as the index VTE encounter. Patients were linked to a claims database and required to be continuously enrolled for six months before the index admission date through six months after the index discharge date. Anticoagulants administered during the index VTE encounter and filled on or within 30 days of discharge were summarized descriptively overall, and by the type of index VTE encounter (IP, No IP) and anticoagulants administered during the index VTE encounter. RESULTS: Among 2,968 eligible patients, mean (SD) age was 64 (16) years, 51% were female, 67% had an IP index VTE encounter, and 77% received anticoagulation therapy during the index VTE encounter. In total, 60% filled a prescription order for anticoagulant within 30 days post-discharge. Of those who received a direct oral anticoagulant (DOAC), warfarin, or parenteral anticoagulant only during the index VTE encounter, 74%, 69%, and 34%, respectively, filled a prescription for the same anticoagulant post-discharge. Patients treated with a DOAC or warfarin during an ED or OBS VTE encounter without a subsequent inpatient hospitalization were more likely to remain on the same anticoagulation therapy post-discharge than those with an inpatient hospitalization (81% vs 69% for DOAC and 75% vs 68% for warfarin). CONCLUSIONS: Many patients treated with anticoagulation therapy during a VTE hospital encounter did not fill a prescription for an anticoagulant within 30 days post-discharge, highlighting an opportunity for improved management of care transitions in this patient population.

Comparative Clinical and Economic Outcomes Associated with Warfarin Versus Apixaban in the Treatment of Patients with Venous Thromboembolism in a Large U.S. Commercial Claims Database.

BACKGROUND: Venous thromboembolism (VTE), constituting deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common cause of vascular-related morbidity and mortality, resulting in a significant clinical and economic burden in the United States each year. Clinical guidelines recommend that patients with DVT and PE without cancer should be initiated on anticoagulation therapy with a direct oral anticoagulant over a vitamin K antagonist. Yet there is limited real-world evidence comparing the economic burden of warfarin and apixaban in treating VTE patients in a large commercially insured population. OBJECTIVE: To compare safety and effectiveness of warfarin and apixaban and evaluate associated economic burden in treating VTE patients in a large U.S. commercial health care claims database. METHODS: The PharMetrics Plus database was used to identify oral anticoagulant (OAC)-naive patients aged ≥ 18 years who initiated apixaban or warfarin within 30 days of a qualifying VTE encounter and had continuous health plan enrollment with medical and pharmacy benefits for 6 months before treatment initiation. Apixaban initiators and warfarin initiators were matched using the propensity score matching (PSM) technique. Cox proportional hazard models were used to assess and compare the risk of major bleeding (MB), clinically relevant nonmajor (CRNM) bleeding, and recurrent VTE. Generalized linear models were used to assess and compare the all-cause health care costs. A 2-part model with bootstrapping was used to evaluate MB- and recurrent VTE-related medical costs. RESULTS: Among 25,193 prematched patients, 13,421 (53.3%) were prescribed warfarin and 11,772 (46.7%) were prescribed apixaban. After 1:1 PSM, 8,858 matched warfarin-apixaban pairs were selected with a mean follow-up of 109 days and 103 days, respectively. Warfarin was associated with a significantly higher risk of MB (HR = 1.52, 95% CI = 1.14-2.04), CRNM bleeding (HR = 1.27, 95% CI = 1017.15-1.40), and recurrent VTE (HR = 1.50, 95% CI = 1.24-1.82) compared with apixaban. Warfarin patients had significantly higher all-cause medical costs per patient per month (PPPM; $2,333 vs. $1,992; P = 0.001), MB-related costs PPPM ($112 vs. $65; P = 0.020), and recurrent VTE-related costs PPPM ($287 vs. $206; P = 0.014) compared with apixaban patients. Warfarin patients had similar all-cause total health care costs PPPM ($2,630 vs. $2,420; P = 0.051) compared with apixaban patients. CONCLUSIONS: Warfarin use was associated with a higher risk of MB, CRNM bleeding, and recurrent VTE compared with apixaban. Warfarin use was also associated with higher all-cause medical costs, MB-related medical costs, and recurrent VTE-related costs PPPM compared with apixaban. DISCLOSURES: This study was funded by Bristol Myers Squibb and Pfizer, which were also involved in the study design, as well as writing and revising of the manuscript. Guo, Rajpura, Okano, and Rosenblatt are employees of Bristol Myers Squibb. Hlavacek, Mardekian, and Russ are employees of Pfizer. Keshishian, Sah, Delinger, and Mu are employees of SIMR, LLC, which received funding from the study sponsors to conduct this study.

Comparison of inpatient admission rates of patients treated with apixaban vs. warfarin for venous thromboembolism in the emergency department.

Objectives: This study evaluated inpatient admission status, hospitalization length of stay (LOS), hospital costs, and readmissions of patients who were diagnosed with venous thromboembolism (VTE) and treated with apixaban or warfarin in the emergency department (ED).Methods: Patients (≥18 years) with an ED visit with a primary discharge diagnosis code of VTE were identified from the Premier Hospital database (8/1/2014-5/31/2018). Patients who received apixaban or warfarin during the ED visit were selected and grouped into two treatment cohorts. Outcomes of ED disposition (discharged or admitted to the inpatient setting), hospital LOS, hospital cost of index event, and rate of 1-month readmissions were compared for the study cohorts.Results: Of the overall study population, 30.5% (n = 12,174; mean age: 59.7 years) received apixaban and 69.5% (n = 27,767; mean age: 59.3 years) received warfarin for VTE in the ED. After adjusting for patient and hospital characteristics, the regression analysis showed that apixaban was associated with a significantly lower likelihood of admission to the inpatient setting vs. warfarin (Odds Ratio [OR]: 0.12, 95% Confidence Interval [CI]: 0.12 to 0.13; p < 0.001). Correspondingly, mean index hospital LOS was 1.42 days shorter (95% CI: -1.47 to -1.36; p < 0.001) and mean index event hospital cost per patient was significantly lower by $4,276 ($3,732 [95% CI: $3,565 to $3,907] vs. $8,008 [95% CI: $7,676 to $8,355]; p < 0.001). Also, the likelihood of all-cause 1-month readmission was significantly lower for patients treated with apixaban vs. warfarin (OR: 0.85, 95% CI: 0.79 to 0.92; p < 0.001).Conclusions: In the real-world setting, VTE patients with an ED visit who were treated with apixaban vs. warfarin had a lower likelihood of being admitted to the inpatient setting, which was reflected in shorter average LOS and lower average index event cost. Additionally, the risk of 1-month readmission was also lower for patients treated with apixaban vs. warfarin.

Cost-Effectiveness of Extended and One-Time Screening Versus No Screening for Non-Valvular Atrial Fibrillation in the USA.

BACKGROUND: There is limited evidence on the clinical and cost benefits of screening for atrial fibrillation (AF) with electrocardiogram (ECG) in asymptomatic adults. METHODS: We adapted a previously published Markov model to evaluate the clinical and economic impact of one-time screening for non-valvular AF (NVAF) with a single 12-lead ECG and a 14-day extended screening with a hand-held ECG device (Zenicor single-lead ECG, Z14) compared with no screening. Clinical events considered included ischemic stroke, systemic embolism, major bleeds, myocardial infarction, and death. Epidemiology and effectiveness data for extended screening were from the STROKESTOP study. Risks of clinical events in NVAF patients were derived from ARISTOTLE. Analyses were conducted from the perspective of a third-party payer, considering a population with undiagnosed NVAF, aged 75 years in the USA. Costs and utilities were discounted at a 3% annual rate. Parameter uncertainty was formally considered via deterministic and probabilistic sensitivity analyses (DSA and PSA). Structural uncertainty was assessed via scenario analyses. RESULTS: In a hypothetical cohort of 10,000 patients followed over their lifetimes, the number of additional AF diagnoses was 54 with 12-lead ECG and 255 with Z14 compared with no screening. Both screening strategies led to better health outcomes (ischemic strokes avoided: ECG 12-lead, 9.8 and Z14, 42.2; quality-adjusted life-years gained: ECG 12-lead, 31 and Z14, 131). Extended screening and one-time screening were cost effective compared with no screening at a willingness-to-pay (WTP) threshold of $100,000 per QALY gained ($58,728/QALY with ECG 12-lead and $47,949/QALY with Z14 in 2016 US dollars). ICERs remained below $100,000 per QALY in all DSA, most PSA runs, and in all scenario analyses except for a scenario assuming low anticoagulation persistence. CONCLUSIONS: Our analysis suggests that, screening the general population at age 75 years for NVAF is cost effective at a WTP threshold of $100,000. Both extended screening and one-time screening for NVAF are expected to provide health benefits at an acceptable cost.

Patient and economic burdens of postherpetic neuralgia in China.

BACKGROUND: Little is known about the patient-reported and economic burdens of postherpetic neuralgia (PHN) among China's urban population. METHODS: This noninterventional study was conducted among adults ≥40 years with PHN who were seeking medical care at eight urban hospitals in China. At one study site, patients completed a questionnaire evaluating the patient-reported disease burden (N=185). The questionnaire consisted of validated patient-reported outcomes including the Brief Pain Inventory (BPI), 5-dimension, 3-level EuroQol (EQ-5D-3L), Medical Outcomes Study Sleep Scale, and Work Productivity and Activity Impairment Questionnaire for Specific Health Problems. Questions on non-pharmacologic therapy and out-of-pocket (OOP) expenses were also included. At all study sites, physicians (N=100) completed a structured review of patient charts (N=828), which was used to derive health care resource utilization and associated costs from the societal perspective. Annual costs in Chinese Yuan Renminbi (RMB) for the year 2016 were converted to US dollars (US$). RESULTS: Patients (N=185, mean age 63.0 years, 53.5% female) reported pain of moderate severity (mean BPI score 4.6); poor sleep quantity (average of 5.3 hrs per night) and quality; and poorer health status on the EQ-5D-3L relative to the general Chinese population. Respondents also reported average annual OOP costs of RMB 16,873 (US$2541) per patient, mainly for prescription PHN medications (RMB 8990 [US$1354]). Substantial work impairment among employed individuals resulted in annual indirect costs of RMB 28,025 (US$4221). In the chart review, physicians reported that patients (N=828) had substantial health resource utilization, especially office visits; 98% had all-cause and 95% had PHN-related office visits. Total annual direct medical costs were RMB 10,002 (US$1507), mostly driven by hospitalizations (RMB 8781 [US$1323]). CONCLUSION: In urban China, PHN is associated with a patient-reported burden, affecting sleep, quality-of-life, and daily activities including work impairment, and an economic burden resulting from direct medical costs and indirect costs due to lost productivity. These burdens suggest the need for appropriate prevention and management of PHN.

Safety, effectiveness, and health care cost comparisons among elderly patients with venous thromboembolism prescribed warfarin or apixaban in the United States Medicare population.

Objective: To compare safety, effectiveness, and healthcare costs of major bleeding (MB), clinically relevant non-major (CRNM) bleeding, recurrent venous thromboembolism (VTE), and all-cause hospitalization among elderly Medicare VTE patients prescribed warfarin vs apixaban.Methods: Using 100% Medicare data, elderly patients prescribed apixaban or warfarin within 30 days after a VTE encounter were identified. Patients had continuous health plan enrollment and no parenteral or oral anticoagulant use ≤6 months preceding the VTE encounter. Cohorts were balanced using 1:1 propensity score matching (PSM). Cox proportional hazard models were used to assess the risk of MB, CRNM bleeding, recurrent VTE, and all-cause hospitalization. Generalized linear and two-part models were used to estimate MB-, recurrent VTE-, and all-cause related costs (per patient per month [PPPM]).Results: In the pre-matched cohort, 25,284 (66.9%) patients were prescribed warfarin and 12,515 (33.1%) apixaban. After 1:1 PSM, 11,363 matched pairs of apixaban-warfarin patients were included for a mean follow-up of 4.0 and 4.4 months, respectively. Matched cohorts had a mean age of 78 years and mean Charlson Comorbidity Index score of 2.9. Warfarin was associated with a higher risk of MB (hazard ratio [HR] = 1.31; 95% confidence interval [CI] = 1.10-1.57) and CRNM bleeding (HR = 1.31; 95% CI = 1.19-1.43) vs apixaban. The risks of recurrent VTE (HR = 0.96; 95% CI = 0.70-1.33) and all-cause hospitalization (HR = 1.05; 95% CI = 0.99-1.12) were similar among warfarin and apixaban patients. Warfarin patients had higher MB-related ($147 vs $75; p = .003) and all-cause costs PPPM ($3,267 vs $3,033; p < .001), but similar recurrent VTE-related medical costs PPPM ($30 vs $36; p = .516) vs apixaban patients.Conclusions: Warfarin was associated with significantly higher risk of MB and CRNM bleeding as well as higher MB-related and all-cause costs vs apixaban patients. Recurrent VTE risk and costs were similar among warfarin and apixaban patients.

Hospital Resource Utilization and Costs Associated With Warfarin Versus Apixaban Treatment Among Patients Hospitalized for Venous Thromboembolism in the United States.

A real-world US database analysis was conducted to evaluate the hospital resource utilization and costs of patients hospitalized for venous thromboembolism (VTE) treated with warfarin versus apixaban. Additionally, 1-month readmissions were evaluated. Of 28 612 patients with VTE identified from the Premier Hospital database (August 2014-May 2016), 91% (N = 26 088) received warfarin and 9% (N = 2524) received apixaban. Outcomes were assessed after controlling for key patient/hospital characteristics. For index hospitalizations, the average length of stay (LOS) was longer (3.8 vs 3.1 days, P < .001; difference: 0.7 days) and mean hospitalization cost higher (US$3224 vs US$2,740, P < .001; difference: US$484) for warfarin versus apixaban-treated patients. During the 1-month follow-up period, warfarin treatment was associated with a greater risk of all-cause readmission (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 1.09-1.48, P = .003), major bleeding (MB)-related readmission (OR: 2.10; 95% CI: 1.03-4.27, P = .04), and any bleeding-related readmission (OR: 1.67; 95% CI: 1.09-2.56, P = .02) versus apixaban. The results of this real-world analysis show that compared to warfarin, apixaban treatment was associated with shorter index hospital stays, lower index hospitalization costs, and reduced risk of MB-related readmissions among hospitalized patients with VTE.

All-Cause, Stroke/Systemic Embolism-, and Major Bleeding-Related Health-Care Costs Among Elderly Patients With Nonvalvular Atrial Fibrillation Treated With Oral Anticoagulants.

In this study, all-cause, stroke/systemic embolism (SE)-related, and major bleeding (MB)-related health-care costs among elderly patients with nonvalvular atrial fibrillation (NVAF) initiating treatment with different oral anticoagulants (OACs) were compared. Patients ≥65 years of age initiating OACs, including apixaban, rivaroxaban, dabigatran, and warfarin, were identified from the Humana Research Database between January 1, 2013, and September 30, 2015. Propensity score matching was used to separately match the different OAC cohorts with the apixaban cohort. All-cause health-care costs and stroke/SE-related and MB-related medical costs per patient per month (PPPM) were compared using generalized linear or 2-part regression models. Compared to apixaban, rivaroxaban was associated with significantly higher all-cause health-care costs (US$2234 vs US$1846 PPPM, P < .001) and MB-related medical costs (US$106 vs US$47 PPPM, P < .001), dabigatran was associated with significantly higher all-cause health-care costs (US$1980 vs US$1801 PPPM, P = .007), and warfarin was associated with significantly higher all-cause health-care costs (US$2386 vs US$1929 PPPM, P < .001), stroke/SE-related medical costs (US$42 vs US$18 PPPM, P < .001), and MB-related medical costs (US$132 vs US$51 PPPM, P < .001). Among elderly patients with NVAF, other OACs were associated with higher all-cause health-care costs than apixaban.

Projecting the cost, utilization, and patient care impact of prescribing extended release non-abuse-deterrent opioids to chronic pain patients.

OBJECTIVES: To estimate healthcare resource utilization, associated costs, and number needed to harm (NNH) from a physician's decision to prescribe extended-release (ER) non-abuse-deterrent opioids (non-ADO) as compared to ER ADOs in a chronic pain population. DESIGN: A 12-month probabilistic simulation model was developed to estimate the reduction of misuse and/or abuse from a physician's prescribing decisions for 10,000 patients. Model inputs included probabilities for opioid misuse and/or abuse-related events, opioid discontinuation, and switching from ADO to non-ADO. Estimated reductions in abuse associated with ADOs were obtained from positive subjective measures using human abuse liability studies. The model was run separately for commercial, Medicare, Medicaid, and Veterans Administration (VA) populations. The difference in healthcare resource utilization and associated costs (2015 USD) between the ADO and non-ADO simulations was calculated. NNH for non-ADO was also calculated. RESULTS: Misuse and/or abuse-related events for patients prescribed ER non-ADOs ranged from 223-1,410 and associated costs ranged from $20-$98 per patient for commercial and Medicare populations, respectively. Prescribing ER ADOs were associated with 87, 289, 264, and 417 fewer misuse and/or abuse-related events, saving $8, $35, $21, and $29 per patient in commercial, VA, Medicaid, and Medicare populations, respectively. NNH ranged from 185 in the commercial population to 40 in the Medicare population. Results were sensitive to decreases in the probability of misuse and/or abuse events but showed reductions. CONCLUSIONS: A physician's decision to prescribe ER ADOs could lead to large reductions in misuse and/or abuse-related events and associated costs across many patient populations.

A systematic review of the effectiveness of policies restricting access to pregabalin.

BACKGROUND: Formularies often employ restriction policies to reduce pharmacy costs. Pregabalin, an alpha-2-delta ligand, is approved for treatment of fibromyalgia (FM); neuropathic pain (NeP) due to postherpetic neuralgia (PHN), diabetic peripheral neuropathy (pDPN), spinal cord injury; and as adjunct therapy for partial onset seizures. Pregabalin is endorsed as first-line therapy for these indications by several US and EU medical professional societies. However, restriction policies such as prior authorization (PA) and step therapy (ST) often favor less costly generic pain medications over pregabalin. METHODS: A structured literature search (PubMed, past 11 years) was conducted to evaluate whether restriction policies against pregabalin support real-world economic and healthcare utilization benefits. RESULTS: Search criteria identified three claims analyses and a modeling study that evaluated patients with NeP and/or FM with and without PA restrictions; three other studies included patients with FM and NeP in plans with ST requirements, and one evaluated a mail order requirement program. All studies evaluated outcomes during follow-up periods of 6 months or longer. Overall, PA, ST, and mail order restriction policies effectively reduced pregabalin usage, but the effects were inconsistent with reducing pharmacy costs and were non-significant for total disease-related medical costs. Two studies (one PA; one ST) reported significantly higher disease-related costs in restricted plans. The modeling study failed to demonstrate cost savings with PA. Opioid usage was higher in PA-restricted plans (two studies). The US Centers for Disease Control and Prevention and several professional NeP guidelines recommend opioid use only in cases when other non-opioid pain therapies have proven ineffective. New US Government taskforce guidelines now seek to reduce opioid exposure. Additionally, in both ST studies, gabapentin utilization (a common ST edit) was significantly increased. Both studies had substantial proportions of FM and pDPN patients and the only pain condition gabapentin is approved to treat in the United States is PHN. CONCLUSION: PA and ST restriction policies significantly decrease utilization of pregabalin, but do not consistently demonstrate cost savings for US health plans. More research is needed to evaluate whether these policies may lead to increased opioid usage as found in some studies. TRIAL REGISTRATION: N/A.

Humanistic and economic burden of fibromyalgia in Japan.

PURPOSE: The aim of this study was to examine the health and economic burden associated with fibromyalgia among adults in Japan. MATERIALS AND METHODS: Data from the 2011-2014 Japan National Health and Wellness Survey (n=115,271), a nationally representative survey of adults, were analyzed. The greedy matching algorithm was used to match the respondents who self-reported a diagnosis of fibromyalgia with those not having fibromyalgia (n=256). Generalized linear models, controlling for covariates (eg, age and sex), examined whether the respondents with fibromyalgia differed from matched controls based on health status (health utilities; Mental and Physical Component Summary scores from Medical Outcomes Study: 12-item Version 2 and 36-item Version 2 Short Form Survey), sleep quality (ie, sleep difficulty symptoms), work productivity (Work Productivity and Activity Impairment Questionnaire - General Health Version 2.0), health care resource use, and estimated annual indirect and direct costs (based on published annual wages and resource use events) in Japanese yen (¥). RESULTS: After adjustment for covariates, respondents with fibromyalgia relative to matched controls scored significantly lower on health utilities (adjusted means =0.547 vs 0.732), Mental Component Summary score (33.15 vs 45.88), and Physical Component Summary score (39.22 vs 50.81), all with P<0.001; these differences exceeded the clinically meaningful levels. In addition, those with fibromyalgia reported significantly poorer sleep quality than those without fibromyalgia. Respondents with fibromyalgia compared with those without fibromyalgia experienced significantly more loss in work productivity and health care resource use, resulting in those with fibromyalgia incurring indirect costs that were more than twice as high (adjusted means =¥2,826,395 vs ¥1,201,547) and direct costs that were nearly six times as high (¥1,941,118 vs ¥335,140), both with P<0.001. CONCLUSION: Japanese adults with fibromyalgia experienced significantly poorer health-related quality of life and greater loss in work productivity and health care use than those without fibromyalgia, resulting in significantly higher costs. Improving the rates of diagnosis and treatment for this chronic pain condition may be helpful in addressing this considerable humanistic and economic burden.