Treatment Patterns, Healthcare Resource Utilization, and Costs of Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma in the US.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among US adults and has experienced a rapidly evolving treatment landscape; yet current data on treatment patterns in clinical practice and economic burden are limited. This study aimed to provide an up-to-date description of real-world characteristics, treatments, and costs of patients with CLL or small lymphocytic lymphoma (SLL). MATERIALS AND METHODS: Using retrospective data from the Optum Clinformatics DataMart database (January 2013 to December 2021), adults with diagnosis codes for CLL/SLL on two different dates were selected. An adapted algorithm identified lines of therapy (LOT). Treatment patterns were stratified by the index year pre- and post-2018. Healthcare resource utilization and costs were evaluated per patient-years. RESULTS: A total of 18 418 patients with CLL/SLL were identified, 5226 patients (28%) were treated with ≥1 LOT and 1728 (9%) with ≥2 LOT. Among patients diagnosed with CLL in 2014-2017 and ≥1 LOT (N = 2585), 42% used targeted therapy and 30% used chemoimmunotherapy in first line (1L). The corresponding proportions of patients diagnosed with CLL in 2018-2021 (N = 2641) were 54% and 16%, respectively. Total costs were numerically 3.5 times higher and 4.9 times higher compared with baseline costs among patients treated with 1L+ and 3L+, respectively. CONCLUSION: This study documented the real-world change in CLL treatment landscape and the substantial economic burden of patients with CLL/SLL. Specifically, targeted therapies were increasingly used as 1L treatments and they were part of more than half of 1L regimens in recent years (2018-2021).

Symptom control in patients with asthma using inhaled corticosteroids/long-acting ß2-agonists (fluticasone furoate/vilanterol or budesonide/formoterol) in the US: a retrospective matched cohort study.

OBJECTIVE: Treatment with fluticasone furoate/vilanterol (FF/VI), an inhaled corticosteroid/long-acting ß2-agonist therapy, reduces the risk of severe asthma exacerbations and improves lung function and symptom control in patients with asthma. However, real-world data remain limited among asthma patients in the United States (US). METHODS: This retrospective cohort study propensity score (PS) matched adult asthma patients initiating once-daily FF/VI 100/25 mcg with patients initiating twice-daily budesonide/formoterol (B/F) 160/4.5 mcg using a US claims database (January 1, 2015-December 31, 2018). Asthma control was measured by the mean number of short-acting ß2-agonist (SABA) canisters dispensed per patient-year (PPY) during follow-up. Time to first, and rates of, overall and severe asthma exacerbations were also measured. RESULTS: After PS matching, 18,531 patients receiving FF/VI were matched to 18,531 patients receiving B/F. Mean SABA canisters dispensed PPY was significantly lower for FF/VI users compared with B/F users (FF/VI: 1.47, B/F: 1.64; p < 0.001). FF/VI use resulted in 13% significantly lower risk of having an overall asthma-related exacerbation and 22% lower risk of a severe exacerbation versus B/F use (overall exacerbation hazard ratio [HR] [95% confidence interval (CI)]: 0.87 [0.82-0.92], p < 0.001; severe exacerbation HR [95% CI]: 0.78 [0.63-0.97], p = 0.027). Asthma-related exacerbation rates per 100 patient-days were also significantly lower for the FF/VI group compared with the B/F group (overall: 0.0475 vs. 0.0558, p < 0.001; severe: 0.0026 vs. 0.0033, p = 0.020). CONCLUSIONS: In real-world practice, initiation of once-daily FF/VI 100/25 mcg in adults with asthma was associated with lower use of SABA and fewer asthma-related exacerbations, which may indicate better asthma control, when compared with use of twice-daily B/F 160/4.5 mcg.

Disease burden and treatment adherence among children and adolescent patients with asthma.

OBJECTIVE: To assess asthma burden and medication adherence in a US de-identified patient level claims database. METHODS: This retrospective observational study used the IQVIA PHARMETRICS PLUS database to identify patients aged 5-17 years, diagnosed with asthma between 01/01/2012-09/30/2017 (asthma cohort), and those initiating treatment with twice-daily inhaled corticosteroids (ICS) or twice-daily ICS/long-acting beta2 agonists (LABA) (treatment cohorts; index date = first dispensing). Patient characteristics, asthma medication, and healthcare resource utilization were assessed over a 12-month baseline period. Treatment cohort endpoints were assessed in a 12-month follow-up period, including: adherence using proportion of days covered (PDC); persistence (no gap >45 days between dispensings). RESULTS: The asthma cohort included 186,868 patients (112,689 children, mean age 7.9 years; 74,179 adolescents, mean age 14.3 years). During baseline, 34.5% used ICS or ICS/LABA, 24% used oral corticosteroids, 11.1% had ≥1 asthma-related emergency department visit, 2.2% had ≥1 asthma-related hospitalization. Among treatment cohorts, 47,276 and 10,247 patients initiated twice-daily ICS and ICS/LABA, respectively (mean ages: 9.9; 12.5 years). Mean PDC adherence to twice-daily ICS and ICS/LABA was 30% and 34% at 6 months (PDC ≥0.8: 4.3%; 6.1%); 21% and 24% at 12 months (PDC ≥0.8: 1.8%; 2.8%). Persistence with twice-daily ICS and ICS/LABA was 10.1% and 14.2% at 6 months; 5.6% and 8.0% at 12 months. CONCLUSIONS: A large disease burden and unmet need exist among US children/adolescent asthma patients, evidenced by low use of, and poor adherence to, ICS-containing medication, the notable proportion of oral corticosteroid users, and higher-than-expected asthma-related emergency department and hospitalization rates.

Effectiveness, safety, and healthcare costs associated with rivaroxaban versus warfarin among venous thromboembolism patients with obesity: a real-world study in the United States.

Prior observational studies suggest rivaroxaban is safe and effective among patients with morbid obesity who suffered a venous thromboembolism (VTE) event, but existing data are more limited in the broader population of VTE patients with obesity. This study assessed VTE recurrence, major bleeding, healthcare resource utilization, and healthcare costs among VTE patients with obesity who received rivaroxaban versus warfarin. VTE patients with obesity who initiated rivaroxaban or warfarin after a first VTE (index date) were identified from the IQVIA PharMetrics® Plus database (01/02/2011-09/30/2019). The follow-up period spanned from the index date until health plan disenrollment, end of data availability, cancer diagnosis/treatment, end of the 12 month post-index period, or (for the analysis of major bleeding) anticoagulant discontinuation or switch. Patient characteristics were balanced using inverse probability of treatment weighting. The weighted rivaroxaban (N = 8666) and warfarin cohorts (N = 5946) were well balanced (mean age = 51 years, females = 52%). Over a 9.6 months mean observation period, rivaroxaban users had a significantly lower risk of VTE recurrence [7.0% vs. 8.2%, HR(95% CI) = 0.85(0.75;0.97)] and a similar risk of major bleeding [4.1% vs. 3.6%, HR(95% CI) = 1.11(0.89;1.37)] relative to warfarin users at 12 months. Relative to warfarin users, rivaroxaban users had significantly fewer all-cause outpatient visits [RR(95% CI) = 0.71(0.70;0.74)]. The higher pharmacy costs incurred by rivaroxaban recipients (cost difference = $1252) were offset by lower medical costs (cost difference = - $2515, all p < 0.05) compared with warfarin recipients. Our findings suggest that rivaroxaban is safe and effective versus warfarin, and associated with lower medical costs among VTE patients with obesity.

Real-World Characteristics, Treatment Patterns, Health Care Resource Use, and Costs of Patients with Diffuse Large B-Cell Lymphoma in the U.S.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma in the U.S., but current real-world data are limited. This study was conducted to describe real-world characteristics, treatment patterns, health care resource utilization (HRU), and health care costs of patients with treated DLBCL in the U.S. MATERIALS AND METHODS: A retrospective study was conducted using the Optum Clinformatics Data Mart database (January 2013 to March 2018). Patients with an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis for DLBCL after October 2015 and no prior International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis for unspecified DLBCL or primary mediastinal large B-cell lymphoma were classified as incident; those with such codes were classified as prevalent. An adapted algorithm identified lines of therapy (e.g., first line [1L]). All-cause HRU and costs were calculated per-patient-per-year (PPPY) among patients with a ≥1L. RESULTS: Among 1,877 incident and 651 prevalent patients with ≥1L, median age was 72 years and 46% were female. Among incident patients, 22.6% had at least two lines (2L), whereas 38.4% of prevalent patients had ≥2L. The most frequent 1L therapy was rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Incident patients had 1.3 inpatient and 42.0 outpatient (OP) visits PPPY, whereas prevalent patients had 0.8 and 31.3 visits PPPY, respectively. Total costs were $137,156 and $81,669 PPPY for incident and prevalent patients, respectively. OP costs were the main driver of total costs at $88,202 PPPY, which were higher within the first year. CONCLUSION: This study showed that a large portion of patients require additional therapy after 1L treatment to manage DLBCL and highlighted the substantial economic burden of patients with DLBCL, particularly within the first year following diagnosis. IMPLICATIONS FOR PRACTICE: Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) carry a substantial clinical and economic burden. A large portion of these patients require additional therapy beyond first-line treatment. There is significant unmet need among patients with DLBCL who require additional therapy beyond first-line treatment. Patients who do not respond to first-line therapy and are not eligible for transplants have very high health care resource utilization and costs, especially in the first 12 months following initiation of treatment.

Real-world impact of antiepileptic drug combinations with versus without perampanel on healthcare resource utilization in patients with epilepsy in the United States.

OBJECTIVES: Combination regimens of antiepileptic drugs (AEDs) with various mechanisms of action (MOA) are commonly used in patients with refractory epilepsy. However, outcomes related to combination AEDs with novel MOA, such as perampanel (PER), are not well described. This study compared healthcare resource utilization (HRU) among recipients of PER-based combinations versus recipients of other non-PER-based combinations. METHODS: This retrospective study used claims data from the Symphony Health's IDV® (Integrated Dataverse) database (August 2012 to July 2018). Patients were aged ≥12 years with epilepsy or non-febrile convulsions, were treated with AED combinations, and had ≥12 and ≥6 months pre- and post-index date, respectively (date of initiation of the second AED in the combination). AEDs were categorized based on MOA: selective non-competitive antagonist of AMPA receptors (i.e., PER), sodium channel blocker (SC), synaptic vesicle protein 2A binding (SV2), and gamma-aminobutyric acid analog (G). Patients were then classified into MOA-based cohorts: PER + SC, PER + SV2, PER + G, SC + SC, SC + SV2, SC + G, SV2 + G, and G + G. HRU outcomes were evaluated during follow-up and compared between PER-based cohorts and non-PER-based cohorts. RESULTS: On average, patients in the PER + SC (N = 3,592), PER + SV2 (N = 2,200), and PER + G (N = 1,313) cohorts were younger and had a lower Quan-Charlson comorbidity index than those in non-PER-based cohorts. PER + SC and PER + SV2 users had significantly fewer all-cause hospitalizations than non-PER-based users (adjusted RR range: 0.66-0.89, all P < 0.05), while PER + G recipients had fewer all-cause hospitalizations than recipients of SV2 + G and G + G (adjusted RR range: 0.92-0.94). Similar trends were observed for epilepsy-related hospitalizations. Across all comparisons, PER-based combinations were associated with significantly lower rates of all-cause clinic/office/outpatient visits relative to non-PER-based combinations (adjusted RR range: 0.69-0.86, all P < 0.05). SIGNIFICANCE: Results showed that patients treated with PER-based combinations had fewer all-cause and epilepsy-related hospitalizations, and fewer all-cause clinic/office/outpatient visits compared with patients treated with most other non-PER-based combinations.

Real-world genetic testing patterns in metastatic castration-resistant prostate cancer.

Aim: To assess the patterns of genetic testing for homologous recombination repair mutations in patients with metastatic castration-resistant prostate cancer (mCRPC) pre-PARP inhibitors approval. Patients & methods: mCRPC patients were selected in an oncology electronic medical records database. Patterns and predictors of testing for ATM, BRCA1/2, CDK12, PALB2 and FANCA gene alterations were assessed. Results: Of 5213 mCRPC patients, 674 (13%) had a documented genetic test. The number of tested patients increased from 1 in 2013 to 313 in 2018 (out of 3161 and 3010 clinically active patients, respectively). Receiving care in an academic oncology center (versus a community-based center) strongly predicted genetic testing (hazard ratio = 2.41). Conclusion: The use of and access to genetic testing pre-PARP inhibitor approval was suboptimal.

Lay abstract In 2017, US guidelines recommended the use of genetic testing in patients with metastatic castration-resistant prostate cancer (mCRPC). While the initial goal of genetic testing was to guide referral to genetic counselling and clinical trial enrollment, it is now also used to identify patients who could benefit from new drugs that target specific molecular defects. Using medical record data of US patients with mCRPC, we found that the rates of genetic testing and the breadth of molecular defects tested were suboptimal from 2013 to 2019. We also found lower rates of genetic testing in patients treated in community-based centers compared with those treated in academic oncology centers. These results underscore the importance of increasing the take up rate of genetic testing in patients with mCRPC to help guide treatment decisions.

Medication adherence in patients with asthma using once-daily versus twice-daily ICS/LABAs.

OBJECTIVE: This real-world observational study compared medication adherence and persistence among patients with asthma receiving the once-daily inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) fluticasone furoate/vilanterol (FF/VI) versus the twice-daily ICS/LABAs budesonide/formoterol (B/F) and fluticasone propionate/salmeterol (FP/SAL). METHODS: This retrospective cohort study conducted using IQVIATM Health Plan Claims Data included patients with asthma ≥18 years of age initiating ICS/LABA therapy with FF/VI, B/F, or FP/SAL between January 1, 2014 and June 30, 2016 (index date). Patients had ≥12 months and ≥3 months of continuous eligibility pre- and post-index date, respectively. Patients receiving FF/VI were separately matched 1:1 with patients receiving B/F or FP/SAL using propensity score matching (PSM) and multivariable regression to balance baseline covariates between cohorts. The primary endpoint was medication adherence, measured by proportion of days covered (PDC). Secondary endpoints included proportion of patients achieving PDC ≥ 0.5 and PDC ≥ 0.8 and persistence with index medication, measured by time to discontinuation (>45-day gap in therapy). RESULTS: After PSM, 3,764 and 3,339 patients receiving FF/VI were matched with patients receiving B/F or FP/SAL, respectively. Mean PDC was significantly higher for FF/VI versus B/F (0.453 vs 0.345; adjusted p < 0.001) and FP/SAL (0.446 vs 0.341; adjusted p < 0.001). The proportion of patients achieving PDC ≥ 0.5 or PDC ≥ 0.8, and treatment persistence were significantly higher for FF/VI versus B/F and FP/SAL (all p < 0.001). CONCLUSIONS: In this real-world study, patients initiating FF/VI had better adherence and lower risk of discontinuing treatment versus B/F or FP/SAL, suggesting that once-daily ICS/LABA treatment might improve adherence and persistence compared with twice-daily alternatives.

Incidence of Major Atherothrombotic Vascular Events among Patients with Peripheral Artery Disease after Revascularization.

BACKGROUND: Patients with peripheral artery disease (PAD) treated with lower extremity revascularization are at increased risk of major atherothrombotic vascular events (acute limb ischemia (ALI), major non-traumatic lower-limb amputation, myocardial infarction (MI), ischemic stroke, and cardiovascular (CV)-related death). This study assessed the incidence of major atherothrombotic vascular events, venous thromboembolism (VTE) events and rates of subsequent lower extremity revascularizations in the real-world among patients with PAD after revascularization. METHODS: Patients aged ≥50 years with PAD who underwent peripheral revascularization were identified from Optum Clinformatics Data Mart claims database (Q1/2014-Q2/2019). The first lower extremity revascularization after PAD diagnosis was defined as index date. Incidence rates of major atherothrombotic vascular events (i.e., composite of ALI, major non-traumatic lower-limb amputation, MI, ischemic stroke, and CV-related death) and VTE were assessed during follow-up as the number of events divided by patient-years of observation (censored at the first event). Rates of subsequent revascularizations and VTE were estimated overall and compared between patients with major atherothrombotic vascular events and those without. RESULTS: Of the 38,439 patients included, 6,675 (17.4%) had a major atherothrombotic vascular event during a median follow-up of 1.0 year. The composite major atherothrombotic vascular and VTE incidence rates were 13.81/100 patient years and 1.77/100 patient years, respectively, and 40.2% of patients experienced subsequent revascularizations. Patients with a post-revascularization major atherothrombotic vascular event had significantly higher rates of subsequent revascularizations (64.6% vs. 35.1%, standardized difference [SD] ≥10%) and VTE (4.6% vs. 2.1%, SD ≥10%) versus those without. CONCLUSION: One-in-six PAD patients aged ≥50 years who underwent peripheral revascularization experienced a major atherothrombotic vascular event within one year, and consequently, experienced higher rates of subsequent revascularizations compared with those without a major atherothrombotic vascular event post-revascularization. These findings highlight the need to improve strategies to prevent major atherothrombotic vascular events after revascularization.

Time-to-first exacerbation, adherence, and medical costs among US patients receiving umeclidinium/vilanterol or tiotropium as initial maintenance therapy for chronic obstructive pulmonary disease: a retrospective cohort study.

BACKGROUND: Adherence to chronic obstructive pulmonary disease (COPD) maintenance medication is important for managing symptoms and exacerbation risk, and is associated with reduced mortality, hospitalizations, and costs. This study compared on-treatment exacerbations, medical costs, and medication adherence in patients with COPD initiating treatment with umeclidinium/vilanterol (UMEC/VI) or tiotropium (TIO). METHODS: This retrospective matched cohort study selected patients from Optum's de-identified Clinformatics Data Mart database who initiated maintenance treatment with UMEC/VI or TIO between 01/01/2014 and 12/31/2017 (index date defined as the first dispensing). Eligible patients were ≥ 40 years of age and had ≥ 12 months continuous health plan coverage pre- and post-index; ≥ 1 medical claim for COPD pre-index or on the index date; no moderate/severe COPD-related exacerbations on the index date; no asthma diagnosis pre- or post-index; no maintenance medication fills containing inhaled corticosteroids, long-acting ß2-agonists, or long-acting muscarinic antagonists pre-index or on the index date; and no fills for both UMEC/VI and TIO on the index date. Outcomes included time-to-first (Kaplan-Meier analysis) and rates of on-treatment COPD-related moderate/severe exacerbations, medication adherence (proportion of days covered [PDC] and proportion of adherent patients [PDC ≥ 0.8]), and COPD-related medical costs per patient per month (PPPM). Propensity score matching was used to adjust for potential confounders. RESULTS: Each cohort included 3929 matched patients. Kaplan-Meier rates of on-treatment COPD-related exacerbations were similar between cohorts (hazard ratio at 12 months; overall: 0.93, moderate: 0.92, severe: 1.07; all p > 0.05). UMEC/VI versus TIO initiators had significantly higher adherence (mean PDC: 0.44 vs 0.37; p < 0.001; proportion with PDC ≥ 0.8: 22.0% vs 16.4%; p< 0.001) and significantly lower mean on-treatment COPD-related total medical costs ($867 vs $1095 PPPM; p = 0.028), driven by lower outpatient visit costs. CONCLUSIONS: These findings provide valuable information for physicians considering UMEC/VI or TIO as initial maintenance therapy options for patients with COPD.

Real-World Adherence in Patients with Metastatic Colorectal Cancer Treated with Trifluridine plus Tipiracil or Regorafenib.

BACKGROUND: Trifluridine and tipiracil (FTD + TPI) and regorafenib (REG) are approved treatments for the treatment of refractory metastatic colorectal cancer (mCRC). This study assesses adherence and duration of therapy with FTD + TPI versus REG and explores the effect of sequencing on adherence. MATERIALS AND METHODS: Adults diagnosed with mCRC were identified in the IQVIA Real-World Data Adjudicated Claims: U.S. database (October 2014-July 2017). The observation period spanned from the index date (first dispensing of FTD + TPI or REG) to the earliest of a switch to another mCRC agent, the end of continuous enrollment, or the end of data availability. Medication possession ratio (MPR), proportion of days covered (PDC), and persistence and time to discontinuation (gap ≥45 days) were compared between FTD + TPI and REG users and among switchers (FTD + TPI-to-REG vs. REG-to-FTD + TPI). RESULTS: A total of 469 FTD + TPI and 311 REG users were identified. FTD + TPI users had higher compliance with an MPR ≥80% (odds ratio [OR], 2.47; p < .001) and PDC ≥80% (OR, 2.77; p < .001). FTD + TPI users had better persistence (82.8% vs. 68.0%; p < .001) and lower risk of discontinuation (hazard ratio [HR], 0.76; p = .006). Among switchers (96 FTD + TPI-to-REG; 83 REG-to-FTD + TPI), those switching from FTD + TPI to REG were more likely to have an MPR ≥80% (OR, 2.91; p < .001) and PDC ≥80% (OR, 4.60; p < .001) compared with REG-to-FTD + TPI switchers while treated with these drugs. Additionally, FTD + TPI-to-REG switchers had a lower risk of first treatment discontinuation (HR, 0.66; p = .009). CONCLUSION: FTD + TPI users had significantly higher adherence and persistence, and patients who were treated with FTD + TPI before switching to REG also had higher adherence and persistence outcomes. IMPLICATIONS FOR PRACTICE: Trifluridine plus tipiracil (FTD + TPI) and regorafenib (REG) prolong survival in refractory metastatic colorectal cancer (mCRC) but have different tolerability profiles. This study assessed real-world adherence to treatment with FTD + TPI versus REG and compared outcomes among patients who switched from FTD + TPI to REG and vice versa. FTD + TPI was associated with significantly higher medication adherence and longer time to discontinuation than REG. Patients treated with FTD + TPI prior to switching to REG also showed higher adherence outcomes. Findings could help inform decision making regarding the choice and sequencing of treatment with FTD + TPI versus REG in patients with mCRC.

EGFR mutation testing and treatment decisions in patients progressing on first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors.

BACKGROUND: The objective of this study was to investigate real-world EGFR mutation testing in patients with metastatic non-small cell lung cancer (NSCLC) upon progression on first-/second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI), and subsequent treatments received. METHODS: Flatiron Health electronic health records-derived database was used to identify adult patients with metastatic NSCLC treated with first-/second-generation EGFR-TKI from 11/2015-09/2017, with start of first EGFR-TKI defined as the index date. Patients were stratified by receipt of EGFR-TKI as first-line (1 L) or later-line (2 L+) treatment. Mutation testing and subsequent therapies following first-/second-generation EGFR-TKI were described. RESULTS: Overall, 782 patients (1 L = 435; 2 L+ =347) were included. Median age was 69.0 years, 63.6% were female, 56.3% were white, 87.1% were treated in community-based practices, and 30.1% of patients died during the study period; median follow-up was 309.0 days. Among the 294 (1 L = 160; 2L+ =134) patients who received subsequent therapies, treatments included chemotherapy only (1 L = 15.6%; 2L+ =21.6%), immunotherapy only (1 L = 13.8%; 2 L+ =41.0%), and targeted therapies (1 L = 70.0%; 2 L+ =36.6%). Specifically, 40 (25.0%) 1 L patients and 7 (5.2%) 2 L+ patients received osimertinib as subsequent therapy. Before the start of subsequent therapy, EGFR T790M resistance mutation testing was performed in 88 (29.9%) patients (1 L = 63 [39.4%]; 2 L+ =25 [18.7%]). Of these patients, 25 (28.4%) were T790M positive, among whom 24 (96.0%) received osimertinib. CONCLUSIONS: A third of patients received subsequent therapies on disease progression; only 30% of these were tested for EGFR-TKI resistance mutation, prior to receiving subsequent therapies. These results highlight the importance of choosing treatments in the 1 L setting that optimize benefits for patients with EGFR-mutated NSCLC.

Risk of Ischemic Stroke in Patients Newly Diagnosed With Heart Failure: Focus on Patients Without Atrial Fibrillation.

BACKGROUND: Heart failure (HF) is associated with an incremental risk of stroke, but limited real-world data exist in patients with HF without atrial fibrillation (AF). OBJECTIVES: To quantify the incremental risk of ischemic stroke among newly diagnosed patients with HF and without AF. METHODS: Adults with HF and ≥18 months of enrollment before their index HF (ie, baseline period) were identified in Truven Health Analytics MarketScan Databases (January 2010-April 2015). Patients without AF during baseline and without an ischemic stroke within 14 days of the index date were propensity score matched 1:1 to individuals with neither HF nor AF and observed for ischemic stroke. A similar analysis was performed for the overall HF population. Incidence rates were compared using incidence rate ratios between HF and non-HF cohorts; Kaplan-Meier analyses with log-rank tests were used to compare incidence rates over time. RESULTS: A total of 66,414 patients with HF were identified, of which 52,005 did not have AF. Patients with HF without AF had significantly higher rates of ischemic stroke than patients without HF without AF during follow-up (incidence rate ratio 1.91 [95% confidence interval 1.75-2.09], P < .001). Ischemic stroke rates remained significantly higher for patients with HF over time among individuals without AF (P < .001 for log-rank test at 12, 24, and 36 months). Similar results were found for the overall HF population. CONCLUSIONS: Even in the absence of AF, patients with HF are at heightened risk of ischemic stroke compared with patients without HF.

Healthcare resource utilization and costs of adverse events among patients with metastatic urothelial cancer in USA.

Aim: To estimate incremental costs and healthcare resource utilization (HRU) associated with select severe adverse events (AEs) and AEs of any severity in patients with metastatic urothelial carcinoma receiving first-line (1L) therapy. Materials & methods: Adults treated with 1L systemic therapy between January 2012 and September 2017 with ≥1 urothelial cancer diagnosis were identified using claims data. Per-patient-per-month cost differences and HRU rate ratios comparing patients with and without select AEs were estimated. Results: Patients with any severe select AEs had higher costs than those without (cost difference = $6130 per-patient-per-month; p < 0.001). Healthcare costs and HRU for patients with select AEs were significantly higher versus those without. Conclusion: Select AEs during 1L therapy for metastatic urothelial carcinoma can result in significant burden to patients and healthcare systems.

Stage III melanoma incidence and impact of transitioning to the 8th AJCC staging system: a US population-based study.

AIM: To estimate incidence of stage III melanoma using the American Joint Committee on Cancer (AJCC) staging, 7th and 8th edition. PATIENTS & METHODS: The SEER US cancer registry was analyzed (2010-2014). AJCC7 stages were recorded in the data; AJCC8 stages were inferred. RESULTS: Of 106,195 melanoma patients, 7669 and 7342 had stage III melanoma by AJCC7 and AJCC8, respectively (95% overlap). Nearly 30% of patients with AJCC7 stage III melanoma were reclassified in a higher stage III group by AJCC8 versus 7% in lower stage group. Regardless of the AJCC edition, incidence of stage III melanoma has increased from 2010 to 2014 both overall and within each stage III group. CONCLUSION: Providing appropriate management to this growing population of high-risk patients is a priority.

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.

Effectiveness and safety of anticoagulants for the treatment of venous thromboembolism in patients with cancer.

Anticoagulation is used to treat venous thromboembolism (VTE) in cancer patients, but may be associated with an increased risk of bleeding. VTE recurrence and major bleeding were assessed in cancer patients treated for VTE with the most currently prescribed anticoagulants in clinical practice. Newly diagnosed cancer patients (first VTE 1/1/2013-05/31/2015) who initiated rivaroxaban, low-molecular-weight heparin (LMWH), or warfarin were identified from Humana claims data and observed until end of eligibility or end of data availability. VTE recurrence was a hospitalization with a primary diagnosis of VTE ≥7 days after first VTE. Major bleeding events on treatment were identified using validated criteria. Cohorts were compared using Kaplan-Meier rates at 6 and 12 months and Cox proportional hazards models. Cohorts were adjusted for their differences at baseline. A total of 2428 patients (rivaroxaban: 707; LMWH: 660; warfarin: 1061) met inclusion criteria. Patient characteristics were well balanced after weighting. There was a trend for lower VTE recurrence rates in rivaroxaban users compared to LMWH users at 6 months (13.2% vs. 17.1%; P = .060) and significantly lower at 12 months (16.5% vs. 22.2%; P = .030) [HR: 0.72, 95% CI: (0.52-0.95); P = .024]. VTE recurrence rates were also lower for rivaroxaban than warfarin users at 6 months (13.2% vs. 17.5%; P = .014) and 12 months (15.7% vs. 19.9%; P = .017) [HR: 0.74, 95% CI: (0.56-0.96); P = .028]. Major bleeding rates were similar across cohorts. This real-world analysis suggests cancer patients with VTE treated with rivaroxaban had significantly lower risk of recurrent VTE and similar risk of bleeding compared to those treated with LMWH or warfarin.

Evaluation of clinical outcomes among nonvalvular atrial fibrillation patients treated with rivaroxaban or warfarin, stratified by renal function
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BACKGROUND: Renal dysfunction increases the risk of thromboembolic and bleeding events in patients with nonvalvular atrial fibrillation (NVAF). MATERIALS AND METHODS: Adult NVAF patients with ≥ 6 months prior to first warfarin or rivaroxaban dispensing were selected from the IMS Health Real-World Data Adjudicated Claims database (05/2011 - 06/2015) with electronic medical records. Ischemic stroke events, thromboembolic events (venous thromboembolism, myocardial infarction, or ischemic stroke), and major bleeding events were compared between patients by renal function identified by 1) relevant ICD-9-CM diagnosis codes and 2) estimated creatinine clearance (eCrCl). Baseline confounders were adjusted using inverse probability of treatment weights. RESULTS: The diagnosis-based analysis included 39,872 rivaroxaban and 48,637 warfarin users (3,572 and 8,230 with renal dysfunction, respectively). The eCrCl-based analysis included 874 rivaroxaban and 1,069 warfarin users (66 and 208 with eCrCl < 60 mL/min, respectively). In the diagnosis-based analysis, rivaroxaban users with renal dysfunction had a significantly lower stroke rate (HR = 0.55, p = 0.0004) compared to warfarin users; rivaroxaban users with and without renal dysfunction had significantly lower thromboembolic event rates (HR = 0.62, p < 0.0001; and HR = 0.64, p < 0.0001, respectively), and similar major bleeding rates to warfarin users. In the eCrCl-based analysis, rivaroxaban users with eCrCl ≥ 60 mL/min had a significantly lower thromboembolic event rate, but other outcomes were not statistically significant. CONCLUSION: Rivaroxaban-treated NVAF patients with diagnosed renal dysfunction had a significantly lower stroke rate compared to warfarin-treated patients. Regardless of renal dysfunction diagnoses, rivaroxaban users had lower thromboembolic event rates compared to warfarin users, and a similar rate of major bleeding. eCrCl-based analysis was limited by a small sample size.
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Health care resource utilization before and after perampanel initiation among patients with epilepsy in the United States.

OBJECTIVE: The purpose of this study was to evaluate changes in health care resource utilization following the initiation of perampanel for the treatment of epilepsy in the United States. METHODS: Health care claims from Symphony Health's Integrated Dataverse database between December 2012 and November 2015 were analyzed. Patients newly initiated on perampanel, having ≥1 epilepsy (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 345.xx, ICD-10-CM code G40.xxx) or nonfebrile convulsion (ICD-9-CM code 780.39, ICD-10-CM code R56.9) diagnosis, and having ≥6 months of baseline and observation periods were included. Patients <12 years old at perampanel initiation were excluded. RESULTS: Of the 2,508 perampanel patients included in the study, the mean [median] (±standard deviation [SD]) age was 35.8 [34] (±16.0) years and 56.2% were female. The mean [median] (±SD) observation duration was 459.8 [462] (±146.3) days in the postperampanel period. The postperampanel period was associated with significantly lower rates of all health care resource utilization outcomes than the pre-period. For the post- versus pre-period, perampanel users had 42.3 versus 53.8 overall hospitalizations per 100 person-years (rate ratio [RR] = 0.80, p < 0.001) and 1,240.2 versus 1,343.8 outpatient visits per 100 person-years (RR = 0.91, p < 0.001). Epilepsy-related hospitalizations and outpatient visits were 25.2 versus 33.6 per 100 person-years (RR = 0.76, p < 0.001) and 327.0 versus 389.0 per 100 person-years (RR = 0.84, p < 0.001), respectively. Additionally, a significantly lower rate of status epilepticus in the post-period (1.8 events per 100 person-years) was observed compared to the pre-period (4.4 events per 100 person-years; RR = 0.43, p < 0.001). The monthly time trend of hospitalizations showed an increasing trend leading up to the initiation of perampanel, after which the hospitalizations decreased steadily. SIGNIFICANCE: Use of perampanel for the treatment of epilepsy was associated with significant reduction in all-cause and epilepsy-related health care resource utilization, including hospitalizations, especially for status epilepticus, and outpatient visits.

Retrospective analysis of the impact of increasing access to long acting reversible contraceptives in a commercially insured population.

BACKGROUND: Unintended pregnancies have been shown to be associated with high costs for the healthcare system, among other adverse impacts, but could still account for up to 51 % of pregnancies in the US. Improvements in contraception among women are needed. Long acting reversible contraceptives (LARCs), which have proved their safety and efficacy, have been found to significantly decrease the risk of unintended pregnancy. Yet they are still marginally employed. This study aims at investigating the evolution of LARC use over 15 years and at assessing the impact of the introduction of newer LARCs on LARC use relative to all contraceptive use. METHODS: This retrospective study identified women with LARC or short acting reversible contraceptive (SARC) claims from a US insurance claims database (01/1999-03/2014). Yearly proportions of LARC users relative to all contraceptive users were reported. Generalized estimating equation models were used to assess the impact of user characteristics, such as age group (15-17, 18-24, 25-34, and 35-44), and of time periods related to the introduction of new LARCs (01/2001: Mirena, 07/2006: Implanon, 01/2013: Skyla) on LARC use. RESULTS: A total of 1,040,978 women were selected. LARC use increased yearly from 0.6 % (1999) to 16.6 % (2013) among contraceptive users. Time periods associated with the introduction of a newer LARC were significant predictors of LARC use; women in 2006-2012 and 2013-2014 were respectively 3.7-fold (95 % CI:3.57-3.74) and 6.6-fold (95 % CI:6.43-6.80) more likely to use LARCs over SARCs relative to women in 2001-2006. The increase in LARC use was especially pronounced in young women. Compared to women aged 18-24 in 2001-2006, women aged 18-24 in 2006-2012 and 2013-2014 were respectively 6.4-fold (95 % CI:5.91-6.86) and 14.7-fold (95 % CI:13.59-15.89) more likely to use LARCs over SARCs. CONCLUSIONS: This broadly representative commercial claim-based study showed that the proportion of privately insured women of childbearing age using LARCs increased over time and that the introduction of newer LARCs corresponded with significant increases in overall LARC use. Future research is needed to assess LARC use in uninsured or publicly-insured populations.