Direct and Indirect Costs of Breast Cancer and Associated Implications: A Systematic Review.

INTRODUCTION: Breast cancer is currently the leading cause of global cancer incidence. Breast cancer has negative consequences for society and economies internationally due to the high burden of disease which includes adverse epidemiological and economic implications. Our aim is to systematically review the estimated economic burden of breast cancer in the United States (US), Canada, Australia, and Western Europe (United Kingdom, France, Germany, Spain, Italy, Norway, Sweden, Denmark, Netherlands, and Switzerland), with an objective of discussing the policy and practice implications of our results. METHODS: We included English-language published studies with cost as a focal point using a primary data source to inform resource usage of women with breast cancer. We focussed on studies published since 2017, but with reported costs since 2012. A systematic search conducted on 25 January 2023 identified studies relating to the economic burden of breast cancer in the countries of interest. MEDLINE, Embase, and EconLit databases were searched via Ovid. Study quality was assessed based on three aspects: (1) validity of cost findings; (2) completeness of direct cost findings; and (3) completeness of indirect cost findings. We grouped costs based on country, cancer stage (early compared to metastatic), and four resource categories: healthcare/medical, pharmaceutical drugs, diagnosis, and indirect costs. Costs were standardized to the year 2022 in US (US$2022) and International (Int$2022) dollars. RESULTS: Fifty-three studies were included. Studies in the US (n = 19) and Canada (n = 9) were the majority (53%), followed by Western European countries (42%). Healthcare/medical costs were the focus for the majority (89%), followed by pharmaceutical drugs (25%), then diagnosis (17%) and indirect (17%) costs. Thirty-six (68%) included early-stage cancer costs, 17 (32%) included metastatic cancer costs, with 23% reporting costs across these cancer stages. No identified study explicitly compared costs across countries. Across cost categories, cost ranges tended to be higher in the US than any other country. Metastatic breast cancer was associated with higher costs than earlier-stage cancer. When indirect costs were accounted for, particularly in terms of productivity loss, they tended to be higher than any other estimated direct cost (e.g., diagnosis, drug, and other medical costs). CONCLUSION: There was substantial heterogeneity both within and across countries for the identified studies' designs and estimated costs. Despite this, current empirical literature suggests that costs associated with early initiation of treatment could be offset against potentially avoiding or reducing the overall economic burden of later-stage and more severe breast cancer. Larger scale, national, economic burden studies are needed, to be updated regularly to ensure there is an ongoing and evolving perspective of the economic burden of conditions such as breast cancer to inform policy and practice.

Incidence and Costs of Clinically Significant Events with Systemic Therapy in Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Cohort Study.

INTRODUCTION: Systemic therapies have been associated with clinically significant events (CSEs) in patients with unresectable hepatocellular carcinoma (uHCC). We evaluated the incidence of CSEs (bleeding, clotting, encephalopathy, and portal hypertension), and their impact on healthcare resource utilization (HCRU) and costs, in patients with uHCC treated with first-line (1L) atezolizumab plus bevacizumab (A + B), lenvatinib (LEN), or sorafenib (SOR) in the USA. METHODS: A retrospective cohort study was performed using medical/pharmacy claims from Optum® Clinformatics® Data Mart. Patients diagnosed with HCC who initiated 1L A + B between June 01, 2020 and December 31, 2020 or LEN/SOR between January 01, 2016 and May 31, 2020 were included. Outcomes included incidence rates of CSEs, HCRU, and costs. Subgroup analysis was performed in patients with no CSEs or ≥ 1 CSE. RESULTS: In total, 1379 patients were selected (A + B, n = 271; LEN, n = 217; SOR, n = 891). Clotting (incidence rate per 100 patient-years [PY] 94.9) and bleeding (88.1 per 100 PY) were the most common CSEs in the A + B cohort. The most common CSEs in the LEN cohort were clotting (78.6 per 100 PY) and encephalopathy (66.3 per 100 PY). Encephalopathy (73.0 per 100 PY) and portal hypertension (72.3 per 100 PY) were the most common CSEs in the SOR cohort. Mean total all-cause healthcare costs per patient per month (PPPM) were $32,742, $35,623, and $29,173 in the A + B, LEN, and SOR cohorts, respectively. Mean total all-cause healthcare costs PPPM were higher in patients who had ≥ 1 CSE versus those who did not (A + B $34,304 versus $30,889; LEN $39,591 versus $30,621; SOR $31,022 versus $27,003). CONCLUSION: Despite improved efficacy of 1L systemic therapies, CSEs remain a concern for patients with uHCC, as well as an economic burden to the healthcare system. Newer treatments that reduce the risk of CSEs, while improving long-term survival in patients with uHCC, are warranted.

Certain treatments for liver cancer can cause serious side effects, including bleeding, blood clots, brain injury (encephalopathy), or increased blood flow to the liver (portal hypertension). We used an insurance database to find out how often these events, known as clinically significant events, occurred in people with liver cancer who were given treatments that target the immune system (immunotherapy) or specific proteins involved in cancer growth and survival (targeted therapy). The study included 1379 patients treated with atezolizumab (immunotherapy) plus bevacizumab (targeted therapy), or lenvatinib or sorafenib alone (both targeted therapies), as their first treatment. Clotting and bleeding were the most common clinically significant events in patients treated with atezolizumab plus bevacizumab, whereas clotting and encephalopathy were the most common clinically significant events with lenvatinib, and encephalopathy and portal hypertension were the most common clinically significant events with sorafenib. On average, for every 100 patients treated for 1 year, there were more than 50 of each of these events. Average healthcare costs per patient per month ranged from around $29,000 to around $36,000 in the three different treatment groups, and were higher in people who had at least one clinically significant event. These results suggest that clinically significant events are common in people with liver cancer who are given various types of treatment. As well as raising concerns for patient safety, these events result in higher costs to healthcare systems. Therefore, newer treatments that are less likely to cause clinically significant events, while improving survival in patients with liver cancer, are needed.

Effectiveness and Safety of Apixaban vs Warfarin in Patients with Venous Thromboembolism with Risk Factors for Bleeding or for Recurrences.

INTRODUCTION: Patients at increased risk of bleeding and recurrent VTE who develop venous thromboembolism (VTE) present challenges for clinical management. This study evaluated the effectiveness and safety of apixaban vs warfarin in patients with VTE who have risk factors for bleeding or recurrences. METHODS: Adult patients with VTE initiating apixaban or warfarin were identified from five claims databases. Stabilized inverse probability treatment weighting (IPTW) was used to balance characteristics between cohorts for the main analysis. Subgroup interaction analyses were conducted to evaluate treatment effects among patients with and without each of the conditions that increased the risk of bleeding (thrombocytopenia and history of bleed) or recurrent VTE (thrombophilia, chronic liver disease, and immune-mediated disorders). RESULTS: A total of 94,333 warfarin and 60,786 apixaban patients with VTE met selection criteria. After IPTW, all patient characteristics were balanced between cohorts. Apixaban (vs warfarin) patients were at lower risk of recurrent VTE (HR [95% confidence interval (CI) 0.72 [0.67-0.78]), major bleeding (MB) (HR [95% CI] 0.70 [0.64-0.76]), and clinically relevant non-major (CRNM) bleeding (HR [95% CI] 0.83 [0.80-0.86]). Subgroup analyses showed generally consistent findings with the overall analysis. For most subgroup analyses, there were no significant interactions between treatment and subgroup strata on VTE, MB and CRNM bleeding. CONCLUSION: Patients with prescription fills for apixaban had lower risk of recurrent VTE, MB, and CRNM bleeding compared with warfarin patients. Treatment effects of apixaban vs warfarin were generally consistent across subgroups of patients at increased risk of bleeding/recurrences.

Treatment persistence and maintenance dose titration among ulcerative colitis patients on biologics: a pooled study of three United States claim databases.

OBJECTIVE: This real-world study evaluated biologic treatment patterns in patients with moderate-to-severe ulcerative colitis (UC). METHODS: IQVIA PharMetrics, IBM MarketScan, and Optum Clinformatics were pooled to identify UC patients with ≥1 claim for UC and ≥1 claim for adalimumab (ADA), golimumab (GOL), infliximab (IFX), or vedolizumab (VDZ). The index date for each biologic was the first claim for that biologic. Patients could be included in >1 cohort if they switched biologics during the identification period. Continuous eligibility for medical/pharmacy benefits was required for 12 months before (baseline) and after (follow-up) the index date. Patients lacking claims for any biologic during baseline were categorized as bio-naïve; those with any biologic claim were categorized as bio-experienced. Persistence was defined as the proportion of patients that remained on the index biologic without a gap between claims of >28 days for ADA, >56 days for GOL, and >112 days for IFX and VDZ. Dose titration was assessed among patients with ≥2 maintenance doses during follow-up among ADA, GOL, and VDZ patients. RESULTS: In total, 6,106 bio-naïve UC patients and 1,027 bio-experienced UC patients were identified. Patients treated with VDZ and IFX had the highest persistence followed by ADA and GOL patients for bio-naïve and bio-experienced, respectively. ADA patients had a numerically higher proportion of patients with 50% dose escalation, followed by VDZ and GOL; 50% dose reduction was observed in ≤1% patients. CONCLUSIONS: In this descriptive study of UC patients without confounder adjustment, VDZ persistence was numerically highest followed by IFX, GOL, and ADA across both populations.

Effectiveness and Safety of Apixaban versus Warfarin in Venous Thromboembolism Patients with Chronic Kidney Disease.

There has been limited evidence reported about the outcomes of oral anticoagulants among patients with venous thromboembolism (VTE) and chronic kidney disease (CKD), especially those with stage V/end-stage renal disease (ESRD). This retrospective cohort analysis of five U.S. claims databases evaluated the risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB) for apixaban versus warfarin among VTE patients diagnosed with CKD, including ESRD. Inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Hazard ratios (HRs) were calculated for recurrent VTE, MB, and CRNMB among patients with CKD who experienced an index VTE. An interaction analysis was conducted to evaluate treatment effects across different stages of CKD. A total of 29,790 VTE patients with CKD were selected for analyses, of whom 10,669 (35.8%) initiated apixaban and 19,121 (64.2%) initiated warfarin. Among IPTW-balanced patient cohorts, the apixaban group had significantly lower risk of recurrent VTE (HR: 0.78; 95% confidence interval [CI]: 0.66-0.92), MB (HR: 0.76; 95% CI: 0.65-0.88), and CRNMB (HR: 0.86; 95% CI: 0.80-0.93) than the warfarin group. When stratified by CKD stage (stage I/II: 8.2%; stage III: 49.4%; stage IV: 12.8%; stage V/ESRD: 12.0%; stage unspecified: 17.6%), no significant interaction was observed for effects of apixaban versus warfarin on recurrent VTE or MB. In summary, apixaban was associated with a significantly lower risk of recurrent VTE and MB than warfarin among VTE patients with CKD. CKD stages did not have significant impact on treatment effects for recurrent VTE and MB.

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.

Effectiveness and Safety of Apixaban Versus Warfarin in Obese Patients with Nonvalvular Atrial Fibrillation Enrolled in Medicare and Veteran Affairs.

Real-world studies have evaluated the use of anticoagulants in obese patients with nonvalvular atrial fibrillation (NVAF), but they have been limited by sample size or the use of diagnosis codes on claims to define obesity. This retrospective study used body weight data of ≥100 kg or a body mass index of ≥30 kg/m2 to identify elderly (aged ≥65 years) NVAF patients with obesity in dually enrolled Veterans Affairs and fee-for-service Medicare patients. It evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients that initiated apixaban versus warfarin. Stabilized inverse probability treatment weighting was used to balance the baseline characteristics between patients prescribed apixaban and warfarin in obese patients. Cox models were used to evaluate the relative risk of stroke/SE and MB. Overall, 35.9% (n = 26,522) of the NVAF population were obese, of which 13,604 apixaban and 12,918 warfarin patients were included. After inverse probability treatment weighting, patient characteristics were balanced. The mean age was 75 years, the mean CHA2DS2-VASc score (Congestive Heart Failure, Hypertension, Age ≥75 [Doubled], Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack [Doubled], Vascular Disease, Age 65-74, Female) was 3.8, the mean HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) Score was ∼2.6, and >98% of patients were males. Obese apixaban patients were associated with a similar risk of stroke/SE (hazard ratio: 0.82; 95% confidence interval: 0.66 to 1.03) and a significantly lower risk of MB (hazard ratio: 0.62; 95% confidence interval: 0.54 to 0.70) versus warfarin. No significant interaction was observed between treatment and obesity status (nonobese, obese/nonmorbid, obese/morbid) for stroke/SE (interaction p = 0.602) or MB (interaction p = 0.385). In obese patients with NVAF, apixaban was associated with a similar risk of stroke/SE and a significantly lower risk of MB versus warfarin.

Persistence, Dosing, and Other Treatment Patterns Among Crohn's Disease Patients Initiating Biologics in United States.

Background: This study examined biologic persistence, dosing, and other treatment patterns among Crohn's disease (CD) patients that initiated adalimumab (ADA), certolizumab pegol (CZP), infliximab (IFX), ustekinumab (UST), and vedolizumab (VDZ). Methods: This descriptive study pooled data from IBM MarketScan, IQVIA PharMetrics, and Optum databases and identified CD patients who initiated the above biologics. Due to low sample size, CZP was not included in the analyses. Persistence was defined as the proportion of patients that remained on the index biologic without a gap of >30 days for ADA and >120 days for UST, IFX, and VDZ between two claims. A sensitivity analysis using fixed gap (90-day) was also conducted. Dose titration (based upon mean maintenance dose) including 50% dose escalation, and 50% dose reduction was assessed among patients with ≥2 maintenance doses during follow-up among ADA, UST, and VDZ patients. Results: After applying all selection criteria, patients were selected into bio-naive (ADA: 2047; IFX: 1127; UST: 296; VDZ: 342) and bio-experienced cohorts (ADA: 300; IFX: 341; UST: 801; VDZ: 593) based on the biologics used. Unadjusted persistence was numerically higher among bio-naive and bio-experienced UST (87.2%, 86.3%) patients followed by VDZ (78.9%, 80.8%), IFX (79.0%, 77.4%), and ADA (64.9%, 60.7%). Similar trends were observed using sensitivity analysis. Dose escalation was numerically higher for ADA patients (16.1%-16.4%) followed by UST (13.4%-16.9%), and VDZ (12.4%-14.7%). Dose reduction followed a similar trend. Conclusions: Among CD patients, unadjusted persistence using variable and fixed gap definition was numerically highest for UST patients whereas dose escalation was numerically highest among ADA patients. Further research is needed to examine treatment patterns after adjusting for confounders and baseline differences among biologic users.

Effectiveness and safety of apixaban, LMWH, and warfarin among high-risk subgroups of VTE patients with active cancer.

OBJECTIVE: This pooled claims database study evaluated the risk of recurrent Venous Thromboembolism (VTE) and major bleeding (MB) among patients with VTE and active cancer prescribed apixaban, low-molecular weight heparin (LMWH), or warfarin stratified by high-risk subgroups. METHODS: Patients diagnosed with VTE in the setting of active cancer who initiated apixaban, LMWH, or warfarin were identified using four US commercial claims databases from 01SEP2014 to the end of the study period (MarketScan: 01MAR2014-30JUNE2017; Optum and Humana: 01MAR2014-31DEC2017; PharMetrics: 01MAR2014-31MAR2018). Stabilized inverse probability treatment weighting (IPTW) was used to balance treatment cohorts. Cox proportional hazard models were used to evaluate the risk of recurrent VTE and MB for each subgroup stratification: VTE risk level based on cancer types, metastatic diagnosis, cancer treatment, chemotherapy, gastrointestinal cancer, and index VTE event type (PE vs. DVT). Statistical significance (p < .10) of the interaction between treatment effects and subgroups was evaluated. RESULTS: Eligible subjects included 3393 apixaban, 6108 LMWH, and 4585 warfarin patients. After IPTW, all patient characteristics were balanced. Analyses stratified by the VTE risk level, metastatic diagnosis, cancer treatment, chemotherapy, gastrointestinal cancer and index VTE event type showed generally consistent results according to the respective subgroup (most of the p values for interaction >0.10). Two significant interactions were observed between apixaban vs. LMWH and VTE risk level (interaction p = .051) and metastatic diagnosis (interaction p < .001) for recurrent VTE; one significant interactions were observed between apixaban vs. LMWH and cancer treatment for MB (interaction p = .074). Additionally, for warfarin vs. LMWH, two significant interactions were observed between treatment and VTE risk level (interaction p = .005) and metastatic diagnosis (interaction p = .002) for recurrent VTE. CONCLUSIONS: Across these high-risk subgroups of VTE cancer patients, treatment outcomes associated with apixaban were generally positive compared to LMWH and warfarin.

Effectiveness and Safety of Apixaban vs. Warfarin in Venous Thromboembolism Patients with Obesity and Morbid Obesity.

This study integrated 5 United States healthcare claims databases to evaluate the risk of recurrent venous thromboembolism (VTE) and major bleeding (MB) among VTE patients who initiated apixaban vs. warfarin, stratified by obesity. Obese and morbidly obese patients were identified based on diagnosis codes. Stabilized inverse probability treatment weighting (IPTW) was conducted to balance observed patient characteristics between treatment cohorts. An interaction analysis was conducted to evaluate treatment effects of apixaban vs. warfarin according to obesity status. Cox proportional hazard models were used to evaluate the risk of recurrent VTE and MB among IPTW weighted obese and morbidly obese patients. A total of 112,024 non-obese patients and 43,095 obese patients were identified, of whom 19,751 were morbidly obese. When stratified by obesity status post-IPTW, no significant interactions were observed for effects of apixaban vs. warfarin on recurrent VTE or MB (interaction p > 0.10). Among IPTW obese and morbidly obese patients, apixaban was associated with a significantly lower risk of recurrent VTE (obese: 0.73 [0.64-0.84]; morbidly obese: 0.65 [0.53-0.80]) and MB (obese: 0.73 [0.62-0.85]; morbidly obese: 0.68 [0.54-0.86]) as compared with warfarin. In this large sample of obese and morbidly obese VTE patients, apixaban had a significantly lower risk of recurrent VTE and MB vs. warfarin.

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.

Treatment patterns and survival in metastatic castration-sensitive prostate cancer in the US Veterans Health Administration.

BACKGROUND: Limited real-world data exist on treatment patterns and outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: A retrospective cohort study was conducted, using the Veterans Health Administration claims database (April 2013-March 2018). Among 369,734 prostate cancer patients, we selected all men who developed metastases within 90 days before or after medical/surgical castration and who received androgen deprivation therapy (ADT). Patients were categorized into four cohorts: ADT-only (± <90-day nonsteroidal anti-androgen [NSAA] use), ADT + NSAA, ADT + docetaxel, and ADT + abiraterone. Main outcomes were treatment patterns, time-to-progression to metastatic castration-resistant disease, and overall survival. Multivariable analysis and sensitivity analysis were conducted. RESULTS: Of 1395 patients, 874 (63%) received ADT-only, 338 (24%) received ADT + NSAA, 108 (8%) received ADT + docetaxel, and 75 (5%) received ADT + abiraterone. Proportions on ADT-only and ADT + NSAA declined (from 66% to 60% and from 31% to 17%, respectively) over the study period, while proportions prescribed ADT + docetaxel or abiraterone increased from 3% to 9% and from 1% to 15%, respectively. Patients treated with ADT + NSAA had similar risks of castration-resistant disease (hazard ratio [HR] 1.05; 95% confidence interval [CI]: 0.87, 1.26) and overall mortality (HR 1.22; 95% CI: 0.97, 1.54) as ADT-only. CONCLUSIONS: Most patients with mCSPC initiating ADT received ADT-only or ADT + NSAA, despite the emergence of docetaxel and novel hormonal therapies. Even in the most recent period (2017 to early 2018), only 24% of men received intensified therapy with agents known to prolong survival versus ADT-only. These data in real-world clinical practice suggest substantial room for improved outcomes in patients with mCSPC.

Effectiveness and Safety of Apixaban, Low-Molecular-Weight Heparin, and Warfarin among Venous Thromboembolism Patients with Active Cancer: A U.S. Claims Data Analysis.

BACKGROUND: This study primarily evaluates the risk of recurrent venous thromboembolism (VTE) and major bleeding (MB) among patients with VTE and active cancer prescribed apixaban, low-molecular-weight heparin (LMWH), or warfarin, with claims data. METHODS: Four U.S. commercial insurance claims databases were used to identify patients with VTE and active cancer who initiated apixaban, LMWH, or warfarin within 30 days following the first VTE event. Stabilized inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Cox proportional hazard models were used to evaluate risk of recurrent VTE and MB. RESULTS: All eligibility criteria were fulfilled by 3,393 apixaban, 6,108 LMWH, and 4,585 warfarin patients. After IPTW, all patient characteristics were balanced. When the follow-up was censored at 6 months, apixaban patients had a lower risk of recurrent VTE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.47-0.81) and MB (HR: 0.63; 95% CI: 0.47-0.86) versus LMWH. Apixaban patients had a lower risk of recurrent VTE (HR: 0.68; 95% CI: 0.52-0.90) and similar risk of MB (HR: 0.73; 95% CI: 0.53-1.00) versus warfarin. Warfarin patients had a similar risk of recurrent VTE (HR: 0.91; 95% CI: 0.72-1.15) and MB (HR: 0.87; 95% CI: 0.68-1.12) versus LMWH. The trends were similar for the entire follow-up; however, apixaban patients had a lower risk of MB versus warfarin patients. CONCLUSION: Patients with VTE and active cancer who initiated apixaban had a lower risk of recurrent VTE and MB compared with LMWH patients. Apixaban patients also had a lower risk of recurrent VTE compared with warfarin patients.

Real-world medication use and economic outcomes in incident systemic lupus erythematosus patients in the United States.

Aims: Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease involving multiple organs systems and places a significant economic burden on SLE patients. There is a literature gap regarding the standard of care and economic burden in SLE patients, their families, and society. This study assessed medication use patterns among SLE patients and generated the annual and total economic burden associated with the illness.Materials and methods: Adult patients with ≥2 medical claims on different dates for SLE diagnoses were identified from 01 January 2013 to 31 December 2015 using two large administrative claims databases representative of the commercially insured US population. Patient demographics and clinical characteristics during 1-year pre-SLE diagnosis were assessed. Outcomes including the proportion of patients who used SLE medications and annual costs were assessed 1-year post-SLE diagnosis. Total costs related to SLE were extrapolated to the US population to estimate the economic burden based on SLE prevalence.Results: A total of 30,086 SLE patients were identified. The most common baseline comorbidities were hypertension and infections. Corticosteroids and hydroxychloroquine were the most common SLE medications. Biologics utilization was minimal. SLE patients had, on average, 26.0 physician visits, 23.7 prescription claims, 1.7 inpatient admissions, and 2.0 hospital days per patient 1-year post-SLE diagnosis. Annual all-cause median costs among all SLE patients were $8712 per patient per year. Total costs ranged between $1.4-1.6 and $2.8-3.2 billion per year, depending on prevalence estimates.Conclusions: Our findings indicate a nominal use of biologics (∼2%) among SLE patients; despite belimumab being one of the few approved treatments for SLE in the USA. These data reveal an unmet need for availability of advanced SLE therapy, and future studies are warranted concerning the underlying causes. SLE is also associated with a substantial economic burden of ≤3.2 billion per year. These findings may assist in future planning and resource allocation.

Evaluating the Effect of Standard of Care Treatment on Burden of Chronic Hepatitis B: A Retrospective Analysis of the United States Veterans Population.

INTRODUCTION: This study aimed to characterize chronic hepatitis B (CHB)-infected patients and estimate the association between nucleos(t)ide analogue (NA) persistence and economic outcomes using data from the Veterans Health Administration (VHA) database. METHODS: Patients (at least 18 years of age) with two or more claims for CHB and at least one pharmacy claim for NA were identified using VHA data from 1 April 2013 to 31 March 2018. The index date was the first NA prescription fill date during 1 October 2014 to 31 March 2017. Persistence and non-persistence to NA treatment were assessed during the first 2 years post index date. Non-persistence was defined as at least one failure to refill medication within 30 days from the run-out date. Generalized linear models were used to compare health care utilization and costs between persistent and non-persistent patients. RESULTS: Among patients treated with NAs (N = 2368), 1428 (60%) were CHB mono-infected and 748 (32%) were HIV co-infected. Total costs per patient per year (PPPY) were $39,240, $29,957, and $55,220 PPPY for NA-treated, mono-infected, and HIV co-infected patients, respectively. An inception cohort of 564 patients (24%), without a NA prescription in the 6 months pre-index period and at least 2 years of follow-up, was created. Persistence among the inception cohort was 29% for first year and 14% for first 2 years. After adjustment for baseline differences, persistent patients had lower cumulative overall health care costs compared to non-persistent patients, with a net cost saving of $851 (p > 0.05) in the first 2 years. CONCLUSION: CHB is associated with considerable economic burden. We observed suboptimal persistence to NAs which decreased over time. Short-term savings could be generated for CHB-infected patients when they remain persistent to NAs.

The atrial FibriLlatiOn real World management registry in the Middle East and Africa: design and rationale.

BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia, affecting 33.5 million patients globally. It is associated with increased morbidity, leading to significant clinical and economic burden. There exist only limited data in the Middle Eastern region from the existing registries. The goal of the FLOW-AF (atrial FibriLlatiOn real World management registry in the Middle East and Africa) registry is to evaluate the characteristics, treatment patterns, and clinical and economic outcomes associated with anticoagulation among patients newly diagnosed with nonvalvular atrial fibrillation in Egypt, Lebanon, the Kingdom of Saudi Arabia, and the United Arab Emirates. METHODS: This study will be a multicountry, multicenter, prospective observational registry aiming to enroll 1446 newly diagnosed nonvalvular atrial fibrillation patients at more than 20 sites across the four countries. During the recruitment period, patients will be included if they were newly diagnosed with nonvalvular atrial fibrillation and had initiated treatment for the prevention of stroke/systemic embolism. Patient data will be assessed prospectively at 6 and 12 months from their enrollment date. Demographics, clinical characteristics, antithrombotic treatments received, clinical outcomes, adverse events, healthcare resource utilization, and direct costs associated with management of nonvalvular atrial fibrillation will be collected and analyzed overall, by country, and by groups created based on treatment, demographics, and clinical characteristics, medical history and risk factors. CONCLUSION: The FLOW-AF registry will provide information on the uptake of oral anticoagulants, treatment patterns, clinical outcomes, and healthcare utilization and costs among newly diagnosed nonvalvular atrial fibrillation patients in the Middle Eastern region.

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.