Healthcare resource utilization of patients with warm autoimmune hemolytic anemia initiating first line therapy of oral corticosteroids with or without rituximab.

This retrospective cohort study described real-world treatment patterns and healthcare resource utilization (HCRU) of patients with warm autoimmune hemolytic anemia (wAIHA) initiating treatment with first-line (1L) oral corticosteroids (OCS) + rituximab (R) compared to 1L OCS. Patients with a wAIHA diagnosis code (D59.11) between 8/2020-3/2022 were identified using US pharmacy and medical claims databases. Patients initiating 1L OCS ± R were identified (date of initiation = 'index date') with a 1-year pre-index period and a variable (minimum 1-year) follow-up period. The final sample comprised 77 1L OCS + R patients and 400 1L OCS patients (~ 60% female, mean age > 64 years). Over the 1-year follow-up, HCRU was higher in the OCS + R cohort with higher mean number of physician office visits (22.9 and 14.4; p < 0.01), including hematology/oncology office visits, and higher utilization of rescue therapy (59.7% and 33.3%; p < 0.01), driven by higher use of injectable corticosteroids. Patients in OCS + R and OCS groups completed 1L therapy after a similar mean duration of 103.5 and 134.6 days, respectively (p = 0.24). In the majority of patients, second-line (2L) therapy was initiated at a similar timepoint: 66.2% OCS + R and 72.0% OCS cohorts (p = 0.31) initiated 2L in a mean of 218.3 and 203.2 days (p = 0.76) after the end of 1L treatment, respectively. The addition of rituximab in 1L did not extend the remission period, with most patients in both cohorts initiating 2L therapy within less than 1 year of completing 1L treatment. 1L OCS + R patients also had substantial HCRU burden. More effective novel therapies are needed to address the high unmet need in wAIHA.

Component Costs of CAR-T Therapy in Addition to Treatment Acquisition Costs in Patients with Multiple Myeloma.

INTRODUCTION: Ciltacabtagene autoleucel (cilta-cel), is a B-cell maturation antigen-directed, genetically modified autologous chimeric antigen receptor T-cell (CAR-T) immunotherapy. It is indicated for treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The objective of this study was to estimate the per-patient US commercial healthcare costs related to cilta-cel (CARVYKTI®) CAR-T therapy (i.e., costs separate from cilta-cel therapy acquisition) for patients with RRMM. METHODS: US prescribing information for cilta-cel, publicly available data, and published literature were used with clinician input to identify the cost components and unit costs associated with administration of cilta-cel. Cost components included apheresis, bridging therapy, conditioning therapy, administration, and postinfusion monitoring for 1 year of follow-up. Adverse event (AE) management costs for all grades of cytokine release syndrome and neurologic toxicities, and additional AEs grade ≥ 3 occurring in > 5% of patients were included in the analysis. RESULTS: The estimated per-patient average costs of cilta-cel CAR-T therapy administered exclusively in an inpatient setting, excluding cilta-cel therapy acquisition costs, totaled US$160,933 over a 12 month period. Costs assuming different proportions of inpatient/outpatient administration (85%/15% and 70%/30%) were US$158,095 and US$155,257, respectively. CONCLUSION: Cost estimates from this analysis, which disaggregates CAR-T therapy costs, provide a comprehensive view of the cost components of CAR-T therapy that can help healthcare decision-makers make informed choices regarding the use of cilta-cel. Real-world costs may differ with improved AE prevention and mitigation strategies.

Comparative effectiveness of ciltacabtagene autoleucel in CARTITUDE-1 versus physician's choice of therapy in the Flatiron Health multiple myeloma cohort registry for the treatment of patients with relapsed or refractory multiple myeloma.

Introduction: Ciltacabtagene autoleucel (cilta-cel) is a novel chimeric antigen receptor T-cell therapy that is being evaluated in the CARTITUDE-1 trial (NCT03548207) in patients with relapsed or refractory multiple myeloma (RRMM) who received as part of their previous therapy an immunomodulatory drug, proteasome inhibitor, and an anti-CD38 monoclonal antibody (i.e., triple-class exposed). Given the absence of a control arm in CARTITUDE-1, this study assessed the comparative effectiveness of cilta-cel and physician's choice of treatment (PCT) using an external real-world control arm from the Flatiron Health multiple myeloma cohort registry. Methods: Given the availability of individual patient data for cilta-cel from CARTITUDE-1 and PCT in Flatiron, inverse probability of treatment weighting was used to adjust for unbalanced baseline covariates of prognostic significance: refractory status, cytogenetic profile, International Staging System stage, time to progression on last regimen, number of prior lines of therapy, years since diagnosis, and age. Comparative effectiveness was estimated for progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS). A range of sensitivity analyses were conducted. Results: Baseline characteristics were similar between the two cohorts after propensity score weighting. Patients with cilta-cel had improved PFS (HR: 0.18 [95% CI: 0.12, 0.27; p < 0.0001]), TTNT (HR: 0.15 [95% CI: 0.09, 0.22; p < 0.0001]), and OS (HR: 0.25 [95% CI: 0.13, 0.46; p < 0.0001]) versus PCT. Cilta-cel treatment benefit was robust and consistent across all sensitivity analyses. Conclusion: Cilta-cel demonstrated significantly superior effectiveness over PCT for all outcomes, highlighting its potential as an effective therapy in patients with triple-class exposed RRMM.

Process, resource and success factors associated with chimeric antigen receptor T-cell therapy for multiple myeloma.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy represents a new frontier in multiple myeloma. It is important to understand critical success factors (CSFs) that may optimize its use in this therapeutic area. Methods: We estimated the CAR-T process using time-driven activity-based costing. Information was obtained through interviews at four US oncology centers and with payer representatives, and through publicly available data. Results: The CAR-T process comprises 13 steps which take 177 days; it was estimated to include 46 professionals and ten care settings. CSFs included proactive collaboration, streamlined reimbursement and CAR-T administration in alternative settings when possible. Implementing CSFs may reduce episode time and costs by 14.4 and 13.2%, respectively. Conclusion: Our research provides a blueprint for improving efficiencies in CAR-T therapy, thereby increasing its sustainability for multiple myeloma.

Patients with multiple myeloma can now be treated with chimeric antigen receptor T-cell (CAR-T) therapy. We studied how CAR-T therapy is used for multiple myeloma. We also studied things that could help make this therapy easier for doctors to use. The CAR-T process takes 13 steps and 177 days. It begins with the choice to use the therapy and ends about 100 days after it is used. The process uses 46 different healthcare professionals and ten different locations. We found several possible changes that can improve this process. Of these changes, three stand out. First, improved teamwork between members of the care team can help them prepare for and resolve possible problems. Second, reducing insurance red tape will make it easier to provide CAR-T therapy to patients. Third, allowing use of CAR-T therapy in places other than hospitals can help more patients receive this therapy. If applied, these three things may lower the time needed to treat patients by 14.4% and may reduce costs by 13.2%.

Healthcare Costs of Multiple Myeloma Patients with Four or More Prior Lines of Therapy, Including Triple-Class Exposure in the United States.

INTRODUCTION: The treatment of multiple myeloma (MM) remains a challenge as patients eventually progress through several lines of therapy (LOTs), requiring use of multiple MM drug classes. In this retrospective US claims-database study, we examined the healthcare costs of patients with MM who received ≥ 4 prior LOTs, including triple-class exposure (TCE). METHODS: Adult patients with MM were selected from the IBM MarketScan Commercial and Medicare claims databases (1 January 2012-30 June 2021). Eligible patients were required to have received at least four prior LOTs, and TCE (i.e., received a proteasome inhibitor, immunomodulatory drug, and anti-CD38-targeted monoclonal antibody) after the first-observed diagnosis of MM. The index date was defined as the initiation date of the first subsequent LOT after meeting the eligibility criteria for the study, and this date had to be after 1 January 2017 to capture contemporary cost estimates. The primary outcome measurements were all-cause and MM-related healthcare costs after the index date. RESULTS: The study population included 68 patients with MM (63% men), with a mean age of 59.8 years. Mean duration from first-observed MM diagnosis until index date averaged 46.7 months. During a mean follow-up of 21.9 months, total all-cause healthcare costs averaged US$757,386 per patient (equivalent to US$34,610 per patient per month). MM-related healthcare costs (US$670,561 per patient) contributed on average 88.5% to the total all-cause healthcare costs; the majority (67.2%) of MM-related healthcare costs were attributed to drug and infusion costs (US$450,952 per patient). CONCLUSIONS: In this retrospective US claims-database study, patients with MM with ≥ 4 prior LOTs, including TCE, continued to experience high healthcare costs that were mostly attributable to anti-myeloma drugs and their administration.

Healthcare Costs Incurred by Patients with Multiple Myeloma Following Triple Class Exposure (TCE) in the US.

INTRODUCTION: Multiple myeloma (MM) is a malignancy of plasma cells; most MM patients will eventually relapse or become refractory to treatment. Treating MM patients remains a challenge since patients eventually progress through several lines of therapy (LOTs), requiring the use of multiple MM drug classes. We examined healthcare resource utilization (HCRU) and the costs incurred by MM patients following triple class exposure (TCE; defined as exposure to a proteosome inhibitor, an immunomodulatory agent, and an anti-CD-38 antibody). METHODS: Adult MM patients were selected from the MarketScan® commercial and Medicare supplemental databases (January 2009-February 2021). From this cohort, patients who had TCE and ≥ 1 subsequent LOT that occurred after January 1, 2017 were included in the study population. The initiation date for the first post-TCE LOT was defined as the index date. All-cause and MM-related HCRU and the associated costs were examined post-index date. RESULTS: A total of 85 MM patients with TCE who initiated ≥ 1 subsequent LOT post-TCE and had ≥ 1 year of follow-up post-index date were included in the study population; mean age on index date was 58.8 years, and 60.0% were male. The time from first-observed MM diagnosis until index date averaged 47.5 months. During an average follow-up of 20.9 months post-index date, 64.7% of patients (N = 55) initiated a second LOT and 35.2% (N = 30) received at least 3 LOTs. During follow-up, mean total all-cause healthcare cost per patient was $722,992 (equivalent to $34,578 per patient per month [PPPM]). Approximately 90.7% ($655,524 per patient) of the total all-cause healthcare costs were MM related, 66.0% of which were MM drug/infusion costs. CONCLUSION: In this real-world US study, MM patients with TCE incurred high healthcare costs, with the majority being MM related and primarily attributed to MM drug and infusion costs.

Applying State-of-the-Art Survival Extrapolation Techniques to the Evaluation of CAR-T Therapies: Evidence from a Systematic Literature Review.

INTRODUCTION: Traditional statistical techniques for extrapolating short-term survival data for anticancer therapies assume the same mortality rate for noncured and "cured" patients, which is appropriate for projecting survival of non-curative therapies but may lead to an underestimation of the treatment effectiveness for potentially curative therapies. Our objective was to ascertain research trends in survival extrapolation techniques used to project the survival benefits of chimeric antigen receptor T cell (CAR-T) therapies. METHODS: A global systematic literature search produced a review of survival analyses of CAR-T therapies, published between January 1, 2015 and December 14, 2020, based on publications sourced from MEDLINE, scientific conferences, and health technology assessment agencies. Trends in survival extrapolation techniques used, and the rationale for selecting advanced techniques, are discussed. RESULTS: Twenty publications were included, the majority of which (65%, N = 13) accounted for curative intent of CAR-T therapies through the use of advanced extrapolation techniques, i.e., mixture cure models [MCMs] (N = 10) or spline-based models (N = 3). The authors' rationale for using the MCM approach included (a) better statistical fits to the observed Kaplan-Meier curves (KMs) and (b) visual inspection of the KMs indicated that a proportion of patients experienced long-term remission and survival which is not inherently captured in standard parametric distributions. DISCUSSION: Our findings suggest that an advanced extrapolation technique should be considered in base case survival analyses of CAR-T therapies when extrapolating short-term survival data to long-term horizons extending beyond the clinical trial duration. CONCLUSION: Advanced extrapolation techniques allow researchers to account for the proportion of patients with an observed plateau in survival from clinical trial data; by only using standard-partitioned modeling, researchers may risk underestimating the survival benefits for the subset of patients with long-term remission. Sensitivity analysis with an alternative advanced extrapolation technique should be implemented and re-assessment using clinical trial extension data and/or real-world data should be conducted as longer-term data become available.

Comparative Effectiveness Research for CAR-T Therapies in Multiple Myeloma: Appropriate Comparisons Require Careful Considerations of Data Sources and Patient Populations.

BACKGROUND AND OBJECTIVE: Registrational trials for ciltacabtagene autoleucel [cilta-cel]) and idecabtagene vicleucel [ide-cel] chimeric antigen receptor T-cell (CAR-T) therapies were single-arm studies conducted with relapse refractory multiple myeloma (MM) patients who were triple-class-exposed (TCE) or triple-class-refractory (TCR). It is critical for researchers conducting comparative effectiveness research (CER) to carefully consider the most appropriate data sources and comparable patient populations. The aim of this study was to identify potential data sources and populations for comparing to single-arm CAR-T trials CARTITUDE-1 (cilta-cel) and KarMMa (ide-cel). METHODS: A 2-part global systematic literature search produced a review of (1) clinical trials of National Comprehensive Cancer Network (NCCN) guideline preferred regimens in previously treated MM, and (2) real-world data cohorts of TCE or TCR populations, published between 1/1/2015 and 12/10/2020, with sample sizes of > 50 patients and reporting survival-related outcomes. Implications on CER and accepted best practices are discussed. RESULTS: Nine clinical trials of NCCN preferred regimens were identified along with five real-world data-based publications. No clinical trials evaluated patients with TCE or TCR MM. Among the real-world data-based publications, two evaluated patients exclusively with TCR MM, two analyzed a mixed population of patients with TCE or TCR MM, and one publication assessed patients exclusively with TCE MM. Real-world data treatment patterns were heterogeneous. CONCLUSION: Current NCCN preferred regimens were not specifically studied in TCE or TCR MM patients, although some studies do include a proportion of these types of patients. Therefore, appropriate matching of populations using either real-world data or patient level clinical trial data is critical to putting trials of novel CAR-Ts (i.e., CARTITUDE-1 or KarMMa) into appropriate comparative context.

Evaluation of machine learning methodology for the prediction of healthcare resource utilization and healthcare costs in patients with critical limb ischemia-is preventive and personalized approach on the horizon?

BACKGROUND: Critical limb ischemia (CLI) is a severe stage of peripheral arterial disease and has a substantial disease and economic burden not only to patients and families, but also to the society and healthcare systems. We aim to develop a personalized prediction model that utilizes baseline patient characteristics prior to CLI diagnosis to predict subsequent 1-year all-cause hospitalizations and total annual healthcare cost, using a novel Bayesian machine learning platform, Reverse Engineering Forward Simulation™ (REFS™), to support a paradigm shift from reactive healthcare to Predictive Preventive and Personalized Medicine (PPPM)-driven healthcare. METHODS: Patients ≥ 50 years with CLI plus clinical activity for a 6-month pre-index and a 12-month post-index period or death during the post-index period were included in this retrospective cohort of the linked Optum-Humedica databases. REFS™ built an ensemble of 256 predictive models to identify predictors of all-cause hospitalizations and total annual all-cause healthcare costs during the 12-month post-index interval. RESULTS: The mean age of 3189 eligible patients was 71.9 years. The most common CLI-related comorbidities were hypertension (79.5%), dyslipidemia (61.4%), coronary atherosclerosis and other heart disease (42.3%), and type 2 diabetes (39.2%). Post-index CLI-related healthcare utilization included inpatient services (14.6%) and ≥ 1 outpatient visits (32.1%). Median annual all-cause and CLI-related costs per patient were $30,514 and $2196, respectively. REFS™ identified diagnosis of skin and subcutaneous tissue infections, cellulitis and abscess, use of nonselective beta-blockers, other aftercare, and osteoarthritis as high confidence predictors of all-cause hospitalizations. The leading predictors for total all-cause costs included region of residence and comorbid health conditions including other diseases of kidney and ureters, blindness of vision defects, chronic ulcer of skin, and chronic ulcer of leg or foot. CONCLUSIONS: REFS™ identified baseline predictors of subsequent healthcare resource utilization and costs in CLI patients. Machine learning and model-based, data-driven medicine may complement physicians' evidence-based medical services. These findings also support the PPPM framework that a paradigm shift from post-diagnosis disease care to early management of comorbidities and targeted prevention is warranted to deliver a cost-effective medical services and desirable healthcare economy.

Healthcare resource utilization and costs associated with venous thromboembolism recurrence in patients with cancer.

Objective: Patients with cancer are at high risk for developing primary but also recurrent venous thromboembolism (VTE). This study examined healthcare utilization (HRU) and costs related to VTE recurrence among cancer patients.Methods: Medical and pharmacy claims from the Humana Database were used to compare HRU (outpatient visits, emergency room visits, hospitalizations, and hospitalization days) and healthcare costs among cancer patients with a single VTE event (between 01/2013 and 06/2015) and those with recurrent VTE during the follow-up period (from initiation of anticoagulant therapy until end of eligibility or data availability). All-cause and VTE-related HRU and costs were evaluated using Poisson regression, and healthcare costs were compared using mean differences reported as per-patient-per-year (PPPY).Results: Of 2,428 newly diagnosed cancer patients who developed VTE, 413 (17.1%) experienced recurrent VTE during the follow-up period (mean = 9 months). Patients with recurrent VTE had higher all-cause and VTE-related HRU and costs compared to those without recurrence. Patients with recurrent VTE also had over 3.19-times more VTE-related hospitalizations (RR [95% CI] = 3.19 [2.93-3.47]), and 3.88-times more VTE-related hospitalization days (RR [95% CI] = 3.88 [3.74-4.02]) than patients without a VTE recurrence. Total VTE-related healthcare costs were $39,641 PPPY among patients with recurrent VTE, $29,142 higher compared to those without recurrence ($10,499 PPPY). This difference was mainly driven by hospitalization costs.Conclusion: Recurrent VTE among cancer patients is associated with significant HRU and healthcare costs, notably hospitalizations. Strategies to reduce VTE recurrence in patients with cancer can contribute to reducing healthcare cost.

Outcomes associated with endovascular treatment among patients with acute ischemic stroke in the USA.

BACKGROUND: Few studies have examined the trends in clinical and economic outcomes of patients with acute ischemic stroke (AIS) who receive endovascular therapy (ET) in the real-world setting. OBJECTIVE: To evaluate characteristics and trends in clinical and economic outcomes among commercially insured patients with AIS undergoing ET between 2011 and 2017. METHODS: Patients with AIS undergoing ET from January 1, 2011 to June 30, 2017 were identified from administrative claims contained in the IBM MarketScan Commercial and Medicare Supplemental databases. The Mann-Kendall trend test was performed to examine clinical and economic trends.Between 2011 and 2017, 3411 patients (mean age 62.85±15 years) with a primary diagnosis of AIS underwent ET (coverage: Commercial 59%, n=2008; Medicare Supplemental 41%, n=1403). In the Commercial cohort, discharge to home increased significantly (from 29.54% to 39.18%, p<0.05). Length of stay declined significantly among the overall cohort (from 10.96 to 9.05 days, p<0.01) and the Medicare Supplemental cohort (from 10.03 to 8.43 days, p<0.05). All-cause 365-day readmission decreased significantly among the overall cohort (from 47.5% to 36.7%, p<0.05) and the Commercial cohort (from 51.54% to 36.43%, p<0.05) but remained unchanged in the Medicare Supplemental cohort. While index procedure cost did not change significantly ($93 955 to $87 906, p=0.8806), total cost significantly declined in the overall cohort (from $166 922 to $130 678, p<0.05). CONCLUSIONS: Although with some variation across the samples studied, outcomes including discharge to home, length of stay, readmission, and total cost associated with endovascular stroke therapy seemed to have improved between 2011 and 2017. Index admission cost remained unchanged.

Endovascular Stroke Therapy Trends From 2011 to 2017 Show Significant Improvement in Clinical and Economic Outcomes.

Background and Purpose- The purpose of this study was to evaluate trends in length of stay, discharge status, and costs among patients with acute ischemic stroke who underwent endovascular therapy (ET) between 2011 and 2017. Methods- Using a retrospective observational study design, acute ischemic stroke patients undergoing ET from 2011 to 2017 were identified in the Premier Healthcare Database. The Mann-Kendall trend test was performed to examine clinical and economic outcomes trends. Results- Among the 505 824 acute ischemic stroke patients, 11 811(2.3%) were treated with ET. Patients receiving ET had a significant increase in home discharge and a significant decrease in mortality (17.7% to 29.6%, P<0.01; 21.6% to 12.8%, P<0.01). There was a significant decline in length of stay from 11.7 days to 8.7 days ( P<0.01). Total index admission costs declined ≈17% from 2011 to 2017 ($50 516.5-$42 026.9, P<0.01). Conclusions- Clinical and economic indicators significantly improved for acute ischemic stroke patients undergoing ET from 2011 to 2017.

Duration of anticoagulant therapy and VTE recurrence in patients with cancer.

PURPOSE: Anticoagulant therapy for at least 3-6 months is currently recommended for treatment of venous thromboembolism (VTE) in patients with cancer, but the optimal duration of treatment is unknown. This study examines the association between the duration of anticoagulation treatment and VTE recurrence in cancer patients. METHODS: The Humana claims database was used to identify newly diagnosed cancer patients who had their first VTE diagnosis between January 1, 2013, and May 31, 2015, and initiated injectable or oral anticoagulant therapy. Follow-up was calculated from the index treatment initiation to the end of eligibility or end of data (June 2015). VTE recurrence was defined as a hospitalization with a primary diagnosis of VTE. Cox proportional hazards models were used to evaluate the risk of VTE recurrence by duration of therapy in patients who discontinued therapy. RESULTS: The study included 1158 patients. Compared to patients treated for 0 to 3 months, VTE recurrences were significantly lower among patients treated for 3 to 6, or over 6 months. After adjustment for baseline characteristics, patients treated for 3 to 6 months (HR [95%CI], 0.53; 0.37-0.76) and more than 6 months (HR [95%CI], 0.48; 0.34-0.68) were still significantly less likely to have VTE recurrences compared to patients treated for 0 to 3 months (both p < 0.01). Findings were similar using a VTE event definition that included outpatient visits. CONCLUSIONS: Among newly diagnosed cancer patients with VTE, anticoagulant therapy lasting more than 3 months was associated with a lower risk of VTE recurrence.

The value of sPESI for risk stratification in patients with pulmonary embolism.

INTRODUCTION: Various risk stratification methods exist for patients with pulmonary embolism (PE). We used the simplified Pulmonary Embolism Severity Index (sPESI) as a risk-stratification method to understand the Veterans Health Administration (VHA) PE population. MATERIALS AND METHODS: Adult patients with ≥ 1 inpatient PE diagnosis (index date = discharge date) from October 2011-June 2015 as well as continuous enrollment for ≥ 12 months pre- and 3 months post-index date were included. We defined a sPESI score of 0 as low-risk (LRPE) and all others as high-risk (HRPE). Hospital-acquired complications (HACs) during the index hospitalization, 90-day follow-up PE-related outcomes, and health care utilization and costs were compared between HRPE and LRPE patients. RESULTS: Of 6746 PE patients, 95.4% were men, 67.7% were white, and 22.0% were African American; LRPE occurred in 28.4% and HRPE in 71.6%. Relative to HRPE patients, LRPE patients had lower Charlson Comorbidity Index scores (1.0 vs. 3.4, p < 0.0001) and other baseline comorbidities, fewer HACs (11.4% vs. 20.0%, p < 0.0001), less bacterial pneumonia (10.6% vs. 22.3%, p < 0.0001), and shorter average inpatient lengths of stay (8.8 vs. 11.2 days, p < 0.0001) during the index hospitalization. During follow-up, LRPE patients had fewer PE-related outcomes of recurrent venous thromboembolism (4.4% vs. 6.0%, p = 0.0077), major bleeding (1.2% vs. 1.9%, p = 0.0382), and death (3.7% vs. 16.2%, p < 0.0001). LRPE patients had fewer inpatient but higher outpatient visits per patient, and lower total health care costs ($12,021 vs. $16,911, p < 0.0001) than HRPE patients. CONCLUSIONS: Using the sPESI score identifies a PE cohort with a lower clinical and economic burden.

Comparison of real-world outcomes in patients with nonvalvular atrial fibrillation treated with direct oral anticoagulant agents or warfarin.

PURPOSE: To compare patients with atrial fibrillation (AF) initiating direct oral anticoagulants (DOACs) versus warfarin on clinical outcomes including stroke, systemic embolism (SE), bleeding events, and cost of care. METHODS: This retrospective observational study used Medicare Advantage Prescription Drug and fully insured commercial claims from the Humana Research Database. Patients with AF who initiated a DOAC or warfarin from January 1, 2012, through September 30, 2015, were included. Date of the first prescription of DOAC or warfarin was the index date. Patients in the DOAC and warfarin groups were matched on propensity scores. Patients were censored at end of enrollment or study period, discontinuation, or switch of index medication. Clinical outcomes were compared in the matched groups using Cox proportional hazards models. Annualized costs and costs adjusted for censoring using Lin's interval method were also compared between the two cohorts. RESULTS: Patients on DOACs had a significantly lower risk of ischemic stroke (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.98), hemorrhagic stroke (HR, 0.65; CI, 0.46-0.92), SE (HR, 0.53; 95% CI, 0.43-0.65), and composite outcome of stroke or SE (HR, 0.78; 95% CI, 0.71-0.86) compared with patients on warfarin. Bleeding risk was not statistically significant (HR, 0.85; 95% CI, 0.71-1.01). While annualized pharmacy costs were higher, annualized medical and total costs were lower in the DOAC group compared with the warfarin group. CONCLUSION: The results of the study indicated that patients on DOACs had lower rates of ischemic stroke, hemorrhagic stroke, SE, and composite outcome of stroke or SE compared with patients on warfarin. No significant differences in bleeding rates between the DOAC and warfarin groups were observed, while total cost of care was lower in the DOAC group.

Predictors of Hospital Length of Stay among Patients with Low-risk Pulmonary Embolism.

BACKGROUND: Increased hospital length of stay is an important cost driver in hospitalized low-risk pulmonary embolism (LRPE) patients, who benefit from abbreviated hospital stays. We sought to measure length-of-stay-associated predictors among Veterans Health Administration LRPE patients. METHODS: Adult patients (aged ≥18 years) with ≥1 inpatient pulmonary embolism (PE) diagnosis (index date = discharge date) between 10/2011-06/2015 and continuous enrollment for ≥12 months pre- and 3 months post-index were included. PE patients with simplified Pulmonary Embolism Stratification Index score 0 were considered low risk; all others were considered high risk. LRPE patients were further stratified into short (≤2 days) and long length of stay cohorts. Logistic regression was used to identify predictors of length of stay among low-risk patients. RESULTS: Among 6746 patients, 1918 were low-risk (28.4%), of which 688 (35.9%) had short and 1230 (64.1%) had long length of stay. LRPE patients with computed tomography angiography (Odds ratio [OR]: 4.8, 95% Confidence interval [CI]: 3.82-5.97), lung ventilation/perfusion scan (OR: 3.8, 95% CI: 1.86-7.76), or venous Doppler ultrasound (OR: 1.4, 95% CI: 1.08-1.86) at baseline had an increased probability of short length of stay. Those with troponin I (OR: 0.7, 95% CI: 0.54-0.86) or natriuretic peptide testing (OR: 0.7, 95% CI: 0.57-0.90), or more comorbidities at baseline, were less likely to have short length of stay. CONCLUSION: Understanding the predictors of length of stay can help providers deliver efficient treatment and improve patient outcomes which potentially reduces the length of stay, thereby reducing the overall burden in LRPE patients.

Clinical and Economic Outcomes in Low-risk Pulmonary Embolism Patients Treated with Rivaroxaban versus Standard of Care.

BACKGROUND: Rivaroxaban, a fixed-dose oral direct factor Xa inhibitor, does not require continuous monitoring and thus reduces the hospital stay and economic burden in low-risk pulmonary embolism (LRPE) patients. Study Question: What is the effectiveness of rivaroxaban versus the standard of care (SOC; low-molecular-weight heparin, unfractionated heparin, warfarin) among LRPE patients in the Veterans Health Administration? STUDY DESIGN: Adult patients with continuous health plan enrollment for ≥12 months pre- and 3 months post-inpatient PE diagnosis (index date=discharge date) between October 1, 2011-June 30, 2015 and an anticoagulant claim during the index hospitalization were included. MEASURES AND OUTCOMES: Patients scoring 0 points on the simplified Pulmonary Embolism Stratification Index were considered low-risk and were stratified into SOC and rivaroxaban cohorts. Propensity score matching (PSM) was used to compare hospital-acquired complications (HACs), PE-related outcomes (recurrent venous thromboembolism, major bleeding, and death), and healthcare utilization and costs between the rivaroxaban and SOC cohorts. RESULTS: Among 6746 PE patients, 1918 were low-risk; of these, 73 were prescribed rivaroxaban, 1546 were prescribed SOC, and 299 were prescribed other anticoagulants during the index hospitalization. After 1:3 PSM, 64 rivaroxaban and 192 SOC patients were included. During the index hospitalization, rivaroxaban users (versus SOC) had similar inpatient length of stay (LOS; 7.0 vs 6.7 days, standardized difference [STD]=1.8) but fewer HACs (4.7% vs 10.4%; STD: 21.7). In the 90-day post-discharge period, PE-related outcome rates were similar between the cohorts (all p>0.05). However, rivaroxaban users had fewer outpatient (15.9 vs 20.4; p=0.0002) visits per patient as well as lower inpatient ($765 vs $2,655; p<0.0001), pharmacy ($711 vs $1,086; p=0.0033), and total costs ($6,270 vs $9,671; p=0.0027). CONCLUSIONS: LRPE patients prescribed rivaroxaban had similar index LOS and PE-related outcomes, but fewer HACs, and lower total costs than those prescribed SOC.

Modeling the impact of real-world adherence to once-daily (QD) versus twice-daily (BID) non-vitamin K antagonist oral anticoagulants on stroke and major bleeding events among non-valvular atrial fibrillation patients.

OBJECTIVES: To estimate the real-world (RW) impact of adherence to once-daily (QD: rivaroxaban and edoxaban) and twice-daily (BID: apixaban and dabigatran) non-vitamin K antagonist (NOACs) on the risk of stroke and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients. METHODS: First, claims from the Optum Clinformatics Data Mart database (July 2012-December 2016) were analyzed. Adult NVAF patients with ≥2 NOAC dispensings (index date) were included. The relationship between NOAC adherence (proportion of days covered ≥80%) and stroke/MB 1-year post-index was evaluated using adjusted Cox proportional hazards models. Second, the natural logarithm of hazard ratios (HRs) was multiplied to a literature-derived mean adherence difference between QD and BID NOACs yielding stroke and MB rates. Third, these rates were multiplied by 1-year Kaplan-Meier rates of stroke and MB which yielded the number of strokes prevented and MBs caused. Annual cost savings were evaluated using literature-based stroke ($81,414/patient) and MB ($63,905/patient) cost estimates. RESULTS: In total, 54,280 patients were included. HRs for adherent vs non-adherent patients were 0.67 (p < .001) for stroke and 1.09 (p = .179) for MB. The claims-derived 1-year Kaplan-Meier rates were 3.0% and 3.4% for strokes and MBs, respectively. For 100,000 AF patients, 64 strokes were prevented (p < .001), and a non-significant number of MBs (n = 15, p < .191) were caused by QD vs BID NOACs annually, which leads to cost savings estimated at $58 million for QD NOACs. CONCLUSION: QD NOACs prevented a significant number of strokes and caused no significant increase in MBs compared to BID NOACs, which leads to significant net cost savings for NVAF patients in the US.

Health-care Cost Impact of Continued Anticoagulation With Rivaroxaban vs Aspirin for Prevention of Recurrent Symptomatic VTE in the EINSTEIN-CHOICE Trial Population.

BACKGROUND: Using data from the Reduced-Dose Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN-CHOICE) trial, this study assessed cost impact of continued anticoagulation therapy with rivaroxaban vs aspirin. METHODS: Total health-care costs (2016 USD) associated with rivaroxaban and aspirin were calculated as the sum of clinical event costs and drug costs from a US managed care perspective. Clinical event costs were calculated by multiplying event rate by cost of care. One-year Kaplan-Meier clinical event rates for recurrent pulmonary embolism, recurrent DVT, all-cause mortality, and bleeding were obtained from EINSTEIN-CHOICE. Cost of care was determined by literature review. Drug costs were the product of drug price (wholesale acquisition cost) and treatment duration. A one-way sensitivity analysis was conducted. RESULTS: Rivaroxaban users had lower per patient per month (PPPM) clinical event costs compared with aspirin users ($123, $243, and $381 for rivaroxaban 10 mg, rivaroxaban 20 mg, and aspirin, respectively). However, vs aspirin, PPPM total health-care costs were $24 higher for patients treated with rivaroxaban 10 mg ($143 higher for rivaroxaban 20 mg) due to higher cost of rivaroxaban. With a 15% discount for rivaroxaban 10 mg, the lower cost of clinical events for the rivaroxaban-treated patients more than fully offset the higher drug costs, and yielded a $19 lower total health-care cost. CONCLUSIONS: Continued therapy with rivaroxaban 10 and 20 mg vs aspirin was associated with lower clinical event costs but higher total health-care costs; with a 15% drug discount rivaroxaban 10 mg had lower total health-care costs than aspirin.