STAT-3 signaling role in an experimental model of nephropathy induced by doxorubicin.

The focal segmental glomerulosclerosis (FSGS) is one of the most frequent glomerulopathy in the world, being considered a significative public health problem worldwide. The disease is characterized by glomerular loss mainly due to inflammation process and collagen fibers deposition. STAT-3 is a transcription factor associated with cell differentiation, migration and proliferation and in renal cells it has been related with fibrosis, acting on the progression of the lesion. Considering this perspective, the present study evaluated the involvement of STAT-3 molecule in an experimental model of FSGS induced by Doxorubicin (DOX). DOX mimics primary FSGS by causing both glomerular and tubular lesions and the inhibition of the STAT3 pathway leads to a decrease in fibrosis and attenuation of kidney damage. We described here a novel FSGS experimental model in a strain of genetically heterogeneous mice which resembles the reality of FSGS patients. DOX-injected mice presented elevated indices of albuminuria and glycosuria, that were significantly reduced in animals treated with a STAT-3 inhibitor (STATTIC), in addition with a decrease of some inflammatory molecules. Moreover, we detected that SOCS-3 (a regulator of STAT family) was up-regulated only in STATTIC-treated mice. Finally, histopathological analyzes showed that DOX-treated group had a significant increase in a tubulointerstitial fibrosis and tubular necrosis, which were not identified in both control and STATTIC groups. Thus, our results indicate that STAT-3 pathway possess an important role in experimental FSGS induced by DOX and may be an important molecule to be further investigated.

Disseminated histoplasmosis in HIV-infected patients: determinants of relapse and mortality in a north-eastern area of Brazil.

Many relapses and deaths resulting from disseminated histoplasmosis (DH) in acquired immunodeficiency syndrome (AIDS) patients have been observed in an endemic area in north-eastern Brazil. The objective of this study was to evaluate the risk factors associated with the clinical outcomes of DH/AIDS coinfection in patients from the state of Ceará, Brazil. A retrospective cohort of AIDS patients, after their hospital discharge due to first DH episode in the period 2002-2008, was followed until December 31, 2010, to investigate the factors associated with relapse and mortality. A total of 145 patients were evaluated in the study. Thirty patients (23.3%) relapsed and the overall mortality was 30.2%. The following variables were significantly (P < 0.05) associated with relapse and overall mortality (univariate analysis): non-adherence to highly active antiretroviral therapy (HAART), irregular use of an antifungal, non-recovery of the CD4+ count and having AIDS before DH; histoplasmosis relapse was also significantly associated with mortality. In the multivariate analysis, non-adherence to HAART was the independent risk factor that was associated with both relapse (Adj OR = 6.28) and overall mortality (Adj OR = 8.03); efavirenz usage was discovered to be significant only for the overall mortality rate (Adj OR = 4.50). Adherence to HAART was the most important variable that influenced the outcomes in this specific population.

Prostate-specific antigen response and clinical progression-free survival in Black and White men with chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide in a real-world setting.

BACKGROUND: In the United States, Black men have a higher incidence of prostate cancer (PC)-related mortality than men of other races. Several real-world studies in advanced PC suggest, however, that Black men respond better to novel hormonal therapies than White men. Data on treatment responses to enzalutamide by race are limited. We assessed real-world prostate-specific antigen (PSA) response and clinical progression-free survival (cPFS) of Black vs. White men with chemotherapy-naïve PC treated with enzalutamide. METHODS: This retrospective cohort study included patients with PC who initiated enzalutamide treatment from 2014 to 2018 in the IntrinsiQ Specialty Solutions™ database, a collection of electronic medical records from community urology practices. Index date was the date of the first prescription for enzalutamide, used as a proxy for metastatic castration-resistant PC (mCRPC). Patients who had undergone chemotherapy and/or abiraterone therapy were excluded. Kaplan-Meier and Cox models adjusted for baseline characteristics were used to estimate PSA response and cPFS by race. RESULTS: The study included 214 Black and 1332 White men with chemotherapy-naïve PC presumed to have mCRPC based on the enzalutamide indication during the study period. Black men were younger and had higher baseline median PSA levels than White men. Enzalutamide therapy duration, follow-up time, and number of post-index PSA tests were similar between races. In multivariable analyses, the risk of patients achieving a ≥ 50% PSA decline was similar, whereas a numerically higher trend of ≥90% PSA decline was observed in Black men (HR 1.23; 95% CI 0.93-1.62 [P = 0.14]). In the multivariable analysis, Black men had significantly better cPFS (HR 0.82; 95% CI 0.68-0.98 [P = 0.03]). CONCLUSIONS: Black and White men with presumed chemotherapy-naïve mCRPC had similar PSA responses when treated with enzalutamide, but Black men had better cPFS than White men. Further research is warranted to validate these findings.

Real-World Biomarker Testing Patterns in Patients With Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) in a US Community-Based Oncology Practice Setting.

INTRODUCTION/BACKGROUND: This study was designed to describe real-world changes in biomarker testing among patients with non-squamous, metastatic non-small cell lung cancer (mNSCLC) in a community oncology setting from 2015 to 2020. PATIENTS AND METHODS: This retrospective study randomly selected 500 adult patients diagnosed with nonsquamous mNSCLC to undergo chart review and data extraction. Data were extracted and validated by 2 independent abstractors. Biomarker testing rates were described before and after national guideline updates and FDA approval of targeted agents. RESULTS: At least 1 biomarker test was received by 89.4% of patients with mNSCLC. Of all patients, 46.6%, 34.6%, and 8.2% received both single-gene and next generation sequencing (NGS)-based testing, single-gene testing only, and NGS-based testing only, respectively. However, there were changes in testing rates at the time of drug approvals for targeted agents. Biomarker testing increased for ALK (45.0% before to 78.3% after ALK-targeted drug approval), BRAF (from 20.0% to 67.8%), EGFR (from 20.0% to 78.2%), NTRK (from 34.6% to 55.7%), and ROS1 (increased from 29.6% before approval to 74.2% after). Biomarker testing increased after changes were made to national guidelines for BRAF (from 18.8% before to 68.1% after inclusion in guidelines), NTRK (from 37.2% to 56.5%), and ROS1 (increased from 40.8% to 74.5% after guideline updates). Targeted therapy was received by 62.4% of patients with a positive biomarker. CONCLUSION: Increases in biomarker testing rates were observed relative to targeted agent approvals and national guideline updates. However, many patients with non-squamous mNSCLC did not receive full genotyping in accordance with national guidelines and represent an opportunity to identify reasons and solutions for barriers to care.

Characteristics and Outcomes in Cases of US Male Patients with Metastatic Breast Cancer Receiving Abemaciclib in Routine Clinical Practice.

INTRODUCTION: Breast cancer in males constitutes approximately 1% of all breast cancer cases globally. Despite extensive treatment experience with abemaciclib in women with metastatic breast cancer (MBC), real-world evidence in male MBC is lacking. METHODS: This analysis was a part of a broader, retrospective study that analyzed electronic medical records and charts of 448 men and women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) MBC who initiated an abemaciclib-containing regimen from January 2017 through September 2019. Data were collected from the Florida Cancer Specialists & Research Institute and the Electronic Medical Office Logistics Health Oncology Warehouse Language™ databases and summarized descriptively. Real-world best response was described: complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). RESULTS: Data for six male patients with MBC who were treated with abemaciclib in combination with an aromatase inhibitor (AI) or fulvestrant are presented. Four patients were aged ≥ 75 years, and four patients had ≥ 3 metastatic sites, including visceral involvement. Abemaciclib was initiated in/after third-line (≥ 3L) in four patients, and patients had history of treatment with AI (n = 4), chemotherapy (n = 3), and/or prior cyclin-dependent kinase 4 and 6 inhibitors (n = 2) in the metastatic setting. Abemaciclib + fulvestrant was the most common abemaciclib-containing regimen (n = 4). Best response was documented in four patients: 1 each with CR, PR, SD, and PD. CONCLUSION: Prevalence of male MBC in this dataset was consistent with expected prevalence in the broader population. Most male patients received an abemaciclib-containing regimen in ≥ 3L, with anti-cancer activity observed despite heavy metastatic burden and prior treatments in a metastatic setting.

Real-World Analysis of Clinical and Demographic Characteristics, Treatment Patterns, and Outcomes in Predominantly Older Patients with HR+/HER2- Metastatic Breast Cancer Receiving Abemaciclib in Routine Clinical Practice.

INTRODUCTION: Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) is the most frequently diagnosed metastatic breast cancer (mBC) subtype. Combinations of endocrine therapy (ET) with cyclin-dependent kinase 4/6 inhibitors (CDK4 & 6is) improve outcomes compared with ET alone. The efficacy and safety of abemaciclib among patients with HR+/HER2- mBC has been demonstrated in the MONARCH clinical trials; however, there is a paucity of real-world evidence, particularly in older patients. METHODS AND MATERIALS: This retrospective cohort study analyzed the electronic medical record data/charts of adult patients with HR+/HER2- mBC receiving abemaciclib in US-based community oncology settings (1 September 2017 to 30 September 2019). Patients with other primary malignancies, clinical trial enrollment, and incomplete charts were excluded. Patient characteristics, treatment attributes and patterns, and real-world outcomes (clinical benefit rate [CBR] and stable disease among patients with response data available, time to chemotherapy [TTC], time to treatment discontinuation [TTD], and progression-free survival [PFS]) were summarized. Multivariable models evaluated the association between demographic/clinical characteristics and outcomes. RESULTS: Of the 448 final patients, 99% were female, with a median age of 67 years (25% were ≥ 75 years) and median follow-up of 11 months; most (60%) initiated abemaciclib within 2 years of mBC diagnosis. Patients received a median of 1 (P25 = 0, P75 = 3) prior line of therapy for mBC before abemaciclib, including other CDK4 & 6is (48%) and prior chemotherapy (31%); most (57%) had visceral disease. The CBR for the overall population was 53%, with 48% achieving stable disease. The median TTC was not reached; median TTD was 249 days (95% confidence interval [CI]: 202, 304). The median PFS was 329 days (95% CI 266, 386). The discontinuation rate of abemaciclib owing to adverse events (30%) trended higher with age (years) (P = 0.027): 18-49 (n = 42; 19%), 50-64 (n = 155; 25%), 65-74 (n = 138; 32%), 75-84 (n = 82; 37%), ≥ 85 (n = 31; 49%); only 23% of patients overall had a dose hold or reduction prior to discontinuation. CONCLUSIONS: These patients were older than those in the MONARCH studies with substantial visceral disease, and prior chemotherapy and CDK4 & 6i use. Discontinuation rates were higher than in previous real-world studies (11.9%), highlighting the need for proactive management to optimize outcomes, particularly in older patients with mBC.

Within-trial economic analysis of resource use from COMET-ICE: A phase 3 clinical trial evaluating sotrovimab for the treatment of patients with COVID-19 at high risk of progression.

BACKGROUND: Final results for the primary endpoint of the COVID-19 Monoclonal antibody Efficacy Trial-Intent to Care Early (COMET-ICE) randomized controlled trial (NCT04545060) showed a 79% (P < 0.001) adjusted relative risk reduction in longer-than-24-hour hospitalization or death due to any cause in high-risk patients with COVID-19 receiving sotrovimab compared with placebo at Day 29. Given the substantial costs associated with COVID-19 hospitalizations, there is a need to quantify the economic impact of clinical trial outcomes to inform decisionmaking. OBJECTIVE: To compare longer-than-24-hour hospitalization costs (primary objective) and total health care costs (secondary objective) associated with COVID-19 care in the sotrovimab vs placebo group in the COMET-ICE trial. METHODS: This was a 2-step, retrospective, post hoc, within-trial economic analysis. Step 1 was a health care claims (MarketScan) database analysis to source unit cost data (2020 USD) from a US payer perspective for COVID-19 care-related resource use from April 1 through June 30, 2020, among adults diagnosed with COVID-19 at high risk of progression (similar to those enrolled in the COMET-ICE trial). Cost per day for an inpatient event stratified by the following maximum respiratory support levels was obtained: no respiratory support or oxygen therapy only, noninvasive ventilation, and invasive mechanical ventilation. Cost per event was obtained for outpatient resource use. Step 2 was the within-trial economic analysis, in which unit costs from Step 1 were applied to the resource use (based on maximum respiratory support and length of stay for inpatient events and number of visits for outpatient events) observed during the first 29 days post-randomization in COMET-ICE. RESULTS: A total of 1,057 patients from the intent-to-treat COMET-ICE population were included (sotrovimab, n = 528; placebo, n = 529). Baseline demographic and clinical characteristics were well balanced between groups. During 29 days of follow-up, mean (SD) costs for the primary endpoint, longer-than-24-hour hospitalization, were $2,827 ($15,545) in the placebo group and $485 ($5,049) in the sotrovimab group (difference, -$2,342; P < 0.0001). Total health care costs were $2,850 ($15,546) in the placebo group and $525 ($5,070) in the sotrovimab group (difference, -$2,325; P = 0.0021). CONCLUSIONS: This post hoc within-trial economic analysis of COMET-ICE data shows that early treatment with sotrovimab vs placebo may be associated with lower longer-than-24-hour hospitalization costs and total health care costs for COVID-19 care in high-risk patients with COVID-19. These findings may be important in informing decision-making regarding use of sotrovimab in clinical practice. DISCLOSURES: Dr Lokhandwala and Ms Farrelly are employees of Xcenda LLC; Xcenda received funding from GSK to support the conduct of this study and did not receive funding for manuscript development. Mr Acharya and Dr Coutinho were employees of Xcenda LLC during the conduct of the study. Mr Bell and Dr Svedsater are employees of, and hold stocks/shares in, GSK. This study was funded by GSK (study 216974) and Vir Biotechnology, Inc. The study sponsors were involved in the study design; collection, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication.

Health Care Resource Utilization and Costs for Metastatic Breast Cancer Patients Newly Treated with Human Epidermal Growth Factor Receptor 2 (HER2)-Targeted Agents.

INTRODUCTION: HER2-positive metastatic breast cancer (mBC) is an incurable disease associated with years of chronic therapy and excess cost. HER2-targeted therapies have shown survival benefit for early-stage and mBC; however, the economic impact of these therapies has not been fully assessed. We evaluated health care resource use (HCRU) and costs of mBC patients treated with HER2-targeted therapy. METHODS: This was a retrospective cohort study using the IQVIA Real-World Data Adjudicated Claims Database (July 1, 2014 to July 31, 2019). Female patients aged ≥18 years with mBC who initiated HER2-targeted therapy in the prior year were identified. The index date was the initiation date of the HER2-targeted agent, after which patients were required to have ≥12 months of follow-up. Annual and cumulative all-cause and BC-related costs (2019 USD) and annual BC-related HCRU were computed in years 1, 2, and 3 following the index date. RESULTS: Following the initiation of HER2-targeted therapy, the mean annual total all-cause costs per patient in years 1 (n = 423), 2 (n = 357), and 3 (n = 166) were $320,892 (SD: $224,343), $235,159 (SD: $185,287), and $226,254 (SD: $197,901), respectively. The mean annual total BC-related costs were $240,048 (SD: $151,230), $175,631 (SD: $148,058), and $165,506 (SD: $159,374) in years 1, 2, and 3, respectively. A major portion of BC-related costs were costs associated with HER2-targeted treatment. The 3-year cumulative all-cause and BC-related total costs were $769,573 (SD: $456,920) and $624,455 (SD: $401,319), respectively. CONCLUSION: Treatment of HER2-positive mBC is a substantial economic burden. A potential approach to minimizing cost and HCRU is to prevent recurrence.

Management of hepatocellular carcinoma from diagnosis in routine clinical practice.

Aim: To assess real-world management of patients diagnosed with hepatocellular carcinoma (HCC) within an integrated delivery network. Materials & methods: A retrospective cohort analysis of adults newly diagnosed with HCC from January 2014 to March 2019. Overall survival and treatment journey were assessed over the entire available follow-up period per patient. Results: Of the 462 patients, 85% had ≥1 treatment. The 24-month overall survival rate (95% CI) from first treatment was 77% (72-82%). Majority of Child-Pugh class A (71%) and B (60%) patients received locoregional therapy first. Half (53.6%) of the patients with liver transplantation first were Child-Pugh class C patients. Sorafenib was the predominant systemic therapy. Conclusion: This integrated delivery network data analysis offers a comprehensive insight into the real-world management of HCC.

Retrospective Analysis of Disease Severity, Health Care Resource Utilization, and Costs Among Patients Initiating Belimumab for the Treatment of Systemic Lupus Erythematosus.

PURPOSE: The goal of this study was to evaluate clinical and economic outcomes associated with the initiation of intravenous (IV) belimumab for the treatment of systemic lupus erythematosus (SLE) in clinical practice in the United States. METHODS: This retrospective study used administrative claims data from the IBM MarketScan Commercial Claims and Encounters Database and the Medicare Supplemental and Coordination of Benefits Database. Data for patients with SLE who initiated (index) IV belimumab were collected for the 12 months before (pre-index) and the 12 months after (post-index) belimumab initiation. Outcomes included SLE disease severity and flares, all-cause health care resource utilization (HCRU) and health care costs, and hospital-based costs and service visits. Post hoc analyses of total hospital-based costs were conducted to further explore drivers of mean post-index costs. FINDINGS: Baseline characteristics (N = 908) are as follows: female, 93.4%; mean (SD) age, 45.6 (11.9) years; mean Charlson Comorbidity Index score, 0.9 (2.0); and moderate or severe disease, 94.9%. Disease activity (SLE flare episodes) was significantly reduced between the pre-index and post-index periods (severe flares, 16.4% vs 10.1% [P < 0.0001]; moderate flares, 92.1% vs 85.6% [P < 0.0001]; and mild flares, 77.4% vs 71.1%; [P = 0.0003]). The proportion of patients receiving oral corticosteroids (OCS) was reduced between the pre-index and post-index periods, especially among patients at higher OCS thresholds (prednisone-equivalent dose: ≥60 mg/d, 7.3% vs 4.2%; >40 mg/d, 14.1% vs 7.9%). From the pre-index to the post-index period, few differences in HCRU were observed, although all-cause physician office visits, outpatient visits, and unique prescriptions filled increased significantly. In the 12-month post-index period, patients had a mean of 12.2 (9.0) encounters (eg, outpatient visit or prescription) associated with IV belimumab. All-cause total, medical, and pharmacy costs increased from the pre-index to the post-index period. Mean all-cause hospital-based costs increased from the pre-index to the post-index period ($7735 [26,603] vs $11,030 [88,086]; P = 0.396). However, the 75th, 90th, and 95th percentile costs decreased from the pre-index to the post-index period ($305, $2107, and $3861, respectively). IMPLICATIONS: After initiation of IV belimumab, disease activity (number of moderate and severe SLE flares) and use of OCS were significantly reduced. However, HCRU and costs, including hospital-based costs, were generally greater in the post-index period. Further studies will increase understanding of SLE, with the specific goals of incorporating disease activity measures and long-term outcomes in studies of HCRU, costs, and patient outcomes.

Within-trial economic analysis of flare data from the BLISS-SC trial of subcutaneous belimumab in systemic lupus erythematosus.

OBJECTIVE: The management of systemic lupus erythematosus (SLE) flares can incur substantial healthcare costs. In the phase III BLISS-SC trial, subcutaneous (SC) belimumab 200 mg plus standard therapy was associated with significant reductions in time to severe flare, and risk of flares, versus placebo plus standard therapy, in adults with active SLE. We evaluated whether the reduction in SLE flares with belimumab SC plus standard therapy translated to lower healthcare costs. METHODS: A retrospective, post hoc economic analysis of BLISS-SC data was conducted. Unit costs per flare from claims data were estimated and applied to flares observed in BLISS-SC to quantify costs associated with treating severe flares (primary objective) or flares of any severity (secondary objective). RESULTS: Of 836 patients (n=556 belimumab, n=280 placebo) analysed (94.4% female, mean (standard deviation, SD) age 38.6 (12.3) years), 13.2% and 62.8% had experienced a severe or mild/moderate flare, respectively. Mean (SD) unit costs per severe, moderate, mild or mild/moderate flare were US$9273 (38 800), US$3048 (9321), US$1671 (6202) and US$2303 (7821), respectively. Adjusted mean costs of treating flares were significantly lower with belimumab SC plus standard therapy than placebo plus standard therapy (severe flare, US$927 lower, p<0.001; flare of any severity, US$1379 lower, p<0.001). CONCLUSIONS: This economic analysis of data from the BLISS-SC trial revealed significant cost reductions were associated with treating SLE flares with belimumab SC plus standard therapy versus placebo plus standard therapy. These findings may help to inform decision making about introducing belimumab to healthcare systems. TRIAL REGISTRATION NUMBER: NCT01484496.

COPD exacerbation costs in the IMPACT study: a within-trial analysis.

OBJECTIVES: Exacerbations account for the greatest proportion of costs associated with chronic obstructive pulmonary disease (COPD). Here we aimed to evaluate, from the US payer perspective, the costs associated with moderate and severe COPD exacerbation events for patients treated with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) compared with FF/VI or UMEC/VI. STUDY DESIGN: This post hoc, within-trial economic analysis used data derived from the InforMing the PAthway of COPD Treatment (IMPACT) study (NCT02164513). METHODS: Treatment groups within the IMPACT trial received either triple therapy with FF/UMEC/VI (100/62.5/25 mcg) or dual therapy (FF/VI [100/25 mcg] or UMEC/VI [62.5/25 mcg]). The primary end point for this IMPACT post hoc analysis was cost differences between the treatment arms related to 1-year on-treatment combined moderate and severe COPD exacerbation events. RESULTS: The final study sample for this within-trial analysis consisted of 10,355 patients, 49% of whom experienced an on-treatment moderate or severe exacerbation during the study. The mean 1-year on-treatment cost estimate associated with combined moderate and severe exacerbations was highest with UMEC/VI and lowest with FF/UMEC/VI ($6205 vs $4913, respectively). Mean cost differences were statistically significant for all pairwise comparisons of FF/UMEC/VI with FF/VI or UMEC/VI (-$549 [95% CI, -$565 to -$533] and -$1292 [95% CI, -$1313 to -$1272], respectively; both P <.0001). CONCLUSIONS: Treatment with FF/UMEC/VI compared with FF/VI or UMEC/VI in the US healthcare system resulted in lower exacerbation-related costs for combined moderate/severe exacerbation events, as well as moderate and severe exacerbations separately.

Cost analysis of COPD exacerbations and cardiovascular events in SUMMIT.

OBJECTIVES: The Study to Understand Mortality and Morbidity in COPD (SUMMIT) trial compared the efficacy of once-daily fluticasone furoate/vilanterol (FF/VI) with placebo, FF monotherapy, and VI monotherapy on mortality in patients with moderate chronic obstructive pulmonary disease (COPD) and a history/increased risk of cardiovascular (CV) disease. We conducted a post hoc economic analysis using data from SUMMIT to evaluate the economic benefits of treating these patients with COPD and CV risk. STUDY DESIGN: Patients (aged 40-80 years, with ≥10 pack-years' smoking history and a risk of CV events) were randomized (1:1:1:1) to receive placebo, FF 100 mcg, VI 25 mcg, or FF/VI 100 mcg/25 mcg. METHODS: This was a post hoc economic analysis to assess the rates and associated costs of the composite end point (acute COPD exacerbations and revascularization/CV composite events) in the SUMMIT trial from a US healthcare payer perspective. RESULTS: Overall, 16,485 patients were evaluated; of these, 5246 (31.8%) experienced an on-treatment composite end point event (28.5% experienced a COPD exacerbation, 4.2% experienced a CV event, and 2.0% underwent a revascularization procedure). The mean estimated 1-year on-treatment combined end point cost was highest for placebo and lowest for FF/VI ($4220 vs $3482, respectively). The reductions in cost versus placebo were significant for all active treatments (P <.0001). The likelihood of experiencing an on-treatment combined end point event was lower for patients treated with FF/VI versus placebo (hazard ratio, 0.81; P <.001). CONCLUSIONS: One-year combined end point event costs were significantly lower for all active treatments versus placebo. Clinicians and payers may be able decrease costs by effectively managing patients' COPD in those with CV risk.

Real-world treatment patterns and outcomes of patients with small cell lung cancer progressing after 2 lines of therapy.

OBJECTIVES: To evaluate treatment patterns, physician-assessed overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) among third-line (3L)-plus small cell lung cancer (SCLC) patients. MATERIALS AND METHODS: Retrospective analysis of a United States (US)-based community oncology electronic medical record (EMR) database was conducted. Target sample included SCLC patients ≥18 years of age whose disease progressed after at least 2 prior treatments. Treatment patterns captured systemic therapy and best supportive care (BSC) in 3L, fourth-line (4L), and fifth-line (5L) settings. ORR, PFS, and OS were evaluated for each line of systemic therapy and OS was also evaluated for BSC. RESULTS: 334 3L SCLC patients received systemic therapy (n = 249) or BSC (n = 85). Mean age (standard deviation [SD]) was 63.7 (9.5), with 72% having extensive disease at initiation of first-line therapy. Of 3L patients, 41% and 12% went on to 4L and 5L, respectively. ORR for systemic therapy in 3L and 4L averaged around 21% while 5L was 12%. Median PFS in 3L systemic therapy was 2.3 months (95% confidence interval [CI]: 1.9, 2.5), which decreased in 4L and 5L. Median OS for 3L systemic therapy was 4.4 months (95% CI: 4.0, 5.5), with 6- and 12-month survival rates of 37% and 11%, respectively. In contrast, median OS for 3L BSC was 0.9 months (95% CI: 0.6, 1.2), with 9% survival rate at 6 months. CONCLUSION: Current treatments utilized in the 3L-plus setting yield limited survival benefit. Furthermore, patients left untreated and placed on BSC typically live less than 1 month. New therapeutic options are thus needed for these patients, where no approved options exist.

COPD affects worker productivity and health care costs.

Purpose: This study aimed to measure the true burden of COPD by calculating incremental direct and indirect costs. Direct medical resource use, productivity metrics, and COPD-specific resource use and costs were also evaluated. Patients and methods: This was a retrospective, observational, matched cohort study using administrative claims data from the Truven Health MarketScan® Commercial Claims and Encounters and the Health and Productivity Management databases (2007-2010). Working-age (18-65 years) patients with COPD were identified as having at least one hospitalization or one emergency department visit or two outpatient visits. Patients in the non-COPD cohort did not have a diagnosis of COPD during the study period. Outcomes were evaluated in the first full calendar year after the year of identification (index). Results: Of the 5,701 patients with COPD identified, 3.6% patients were frequent exacerbators (≥2), 10.4% patients were infrequent exacerbators (1), and 86% patients were non-exacerbators (0). When compared with the 17,103 patients without COPD, the incremental direct cost of COPD was estimated at $6,246/patient/year (95% confidence interval: $4,620, $8,623; P<0.001). Loss in productivity was significantly greater in patients with COPD, with an average of 5 more days/year of absence from work and incremental indirect costs from short-term disability of $641 (P<0.001). Direct costs for frequent exacerbators ($17,651/year) and infrequent exacerbators ($14,501/year) were significantly higher than those for non-exacerbators ($11,395, P<0.001). Conclusion: Working-age patients with COPD incur statistically significantly higher direct and indirect costs and use more resources compared with those who do not have COPD.

Confirming the timing of phase-based costing in oncology studies: a case example in advanced melanoma.

AIMS: The utilization of healthcare services and costs among patients with cancer is often estimated by the phase of care: initial, interim, or terminal. Although their durations are often set arbitrarily, we sought to establish data-driven phases of care using joinpoint regression in an advanced melanoma population as a case example. METHODS: A retrospective claims database study was conducted to assess the costs of advanced melanoma from distant metastasis diagnosis to death during January 2010-September 2014. Joinpoint regression analysis was applied to identify the best-fitting points, where statistically significant changes in the trend of average monthly costs occurred. To identify the initial phase, average monthly costs were modeled from metastasis diagnosis to death; and were modeled backward from death to metastasis diagnosis for the terminal phase. Points of monthly cost trend inflection denoted ending and starting points. The months between represented the interim phase. RESULTS: A total of 1,671 patients with advanced melanoma who died met the eligibility criteria. Initial phase was identified as the 5-month period starting with diagnosis of metastasis, after which there was a sharp, significant decline in monthly cost trend (monthly percent change [MPC] = -13.0%; 95% CI = -16.9% to -8.8%). Terminal phase was defined as the 5-month period before death (MPC = -14.0%; 95% CI = -17.6% to -10.2%). LIMITATIONS: The claims-based algorithm may under-estimate patients due to misclassifications, and may over-estimate terminal phase costs because hospital and emergency visits were used as a death proxy. Also, recently approved therapies were not included, which may under-estimate advanced melanoma costs. CONCLUSIONS: In this advanced melanoma population, optimal duration of the initial and terminal phases of care was 5 months immediately after diagnosis of metastasis and before death, respectively. Joinpoint regression can be used to provide data-supported phase of cancer care durations, but should be combined with clinical judgement.

Clinical and economic outcomes associated with the use of fluticasone propionate 250 mcg and salmeterol 50 mcg combination versus tiotropium bromide 18 mcg as initial maintenance treatment for chronic obstructive pulmonary disease in managed care.

AIMS: To examine the clinical and economic outcomes associated with the use of long-acting bronchodilators for initial maintenance treatment of chronic obstructive pulmonary disease (COPD) by analyzing health insurance claims data in the US. METHODS: A retrospective, observational, matched cohort study used health insurance claims data (January 2008 to June 2013) to assess COPD-related outcomes for subjects aged ≥40 years. Subjects were assigned to a study cohort according to the first observed prescription fill for a long-acting bronchodilator (fluticasone propionate 250 mcg/salmeterol 50 mcg [FSC] or tiotropium bromide 18 mcg [TIO]). The analysis period for each subject comprised a 1-year pre-index date and 1-year post-index date. Primary outcome measure was total COPD-related costs per-patient per-year (PPPY) during the follow-up period. Secondary outcome measures included COPD-related exacerbations and the components of COPD-related costs. RESULTS: Overall, 24,040 subjects were identified; the analysis sample consisted of 19,090 subjects (9,545 per cohort) with no significant differences between cohorts. Mean COPD-related total costs PPPY were numerically lower among the FSC cohort; however, the difference was not statistically significant ($2,224 [±4,108] vs $2,352 [±3,721], p = .057). There was no difference between cohorts for COPD-related medical costs (p = .894). COPD-related pharmacy costs were significantly, yet modestly, lower in the FSC cohort compared with the TIO cohort ($1,160 [±1,106] vs 1,275 [±1,110], p < .001). There were no statistically significant differences in the rate or number of exacerbations between the matched cohorts. LIMITATIONS: While propensity scoring achieved balance in baseline characteristics, some residual confounding unobserved in the database may be present. CONCLUSIONS: Few clinical and economic differences between subjects initiating maintenance therapy with FSC or TIO were observed.

Incremental burden of type 2 diabetes in patients experiencing cardiovascular hospitalizations.

OBJECTIVE: To evaluate the incremental economic burden of type 2 diabetes in patients experiencing cardiovascular (CV) hospitalizations. RESEARCH DESIGN AND METHODS: Adults with ≥1 CV hospitalization were identified using a US-based healthcare claims database from 1 July 2011 to 30 June 2014. Outcomes for patients surviving the index hospitalization were compared between patients with vs. without type 2 diabetes (cohorts were identified in the pre-index period). Subsequent CV hospitalizations were evaluated using Cox proportional hazards models. All-cause and CV-related healthcare resource utilization (HCRU) and costs captured on a per-patient per-month (PPPM) basis during a variable follow-up period were evaluated using appropriate multivariable regression models. RESULTS: Of 316,207 patients with ≥1 CV hospitalization, 23% had comorbid type 2 diabetes. The mean age ± SD was 62.6 ± 12.3 years and 64.4% were male. During follow-up, the type 2 diabetes cohort had a 19% higher risk of subsequent CV hospitalizations compared to the non-type-2-diabetes cohort (p < .001). This difference in risk was highest in patients aged 35-44 years. Subsequent all-cause hospitalizations for the type 2 diabetes cohort were longer (mean length of stay, 6.7 vs. 6.3 days; p < .001), with higher total bed-days PPPM (mean, 0.52 vs. 0.43; p < .001), compared to the non-type-2-diabetes cohort. The type 2 diabetes cohort had a significantly higher incremental cost for both the index CV hospitalization (mean cost difference, $1046; p < .001) and all-cause costs PPPM following discharge (mean cost difference, $749; p < .001). CONCLUSIONS: Comorbid type 2 diabetes was associated with an increased risk of subsequent CV hospitalizations and higher costs and HCRU during the follow-up period.

Long-term opioid users with chronic noncancer pain: Assessment of opioid abuse risk and relationship with healthcare resource use.

OBJECTIVE: Identify opioid abuse risk factors among chronic noncancer pain (CNCP) patients receiving long-term opioid therapy and assess healthcare resource use (HRU) among patients at elevated abuse risk. DESIGN: Data were obtained from an integrated administrative claims database. Classification and Regression Tree (CART) analysis identified risk factors potentially predictive of opioid abuse, which were used to classify the overall population into cohorts defined by levels of abuse risk. Multivariable logistic regression compared HRU across risk cohorts. SETTING: Retrospective cohort study. PATIENTS, PARTICIPANTS: 21,072 patients aged ≥18 years diagnosed with ≥1 of 5 types of CNCP and a prescription for Schedule II or III/IV opioid medication used long-term (≥90 days). MAIN OUTCOME MEASURES: (1) Opioid abuse risk factors; (2) HRU differences between risk cohorts. RESULTS: CART analysis identified four groups at elevated opioid abuse risk defined by three factors (age, daily opioid dose, and total days' supply of opioids); sensitivity: 70.3 percent, specificity: 74.1 percent, and positive predictive value: 5.6 percent. The analysis results were used to classify patients into low-risk (72.5 percent), at-risk (25.4 percent), and opioid-abuser (2.2 percent) cohorts. In multivariable analysis, emergency department (ED) use was higher among at-risk vs low-risk patients (odds ratio [OR]: 1.14; p<0.05); hospitalization and ED visits were higher for opioid-abusers vs low-risk patients (OR: 2.33 and 2.14, respectively; p<0.05). CONCLUSIONS: This study identifies a subpopulation of CNCP patients at risk of opioid abuse. However, limited sensitivity and specificity of criteria defining this subpopulation reinforce the importance of physician discretion in patient-level treatment decisions.

The cost of cardiovascular-disease-related death in patients with type 2 diabetes mellitus.

OBJECTIVES: To assess the magnitude of difference in all-cause healthcare resource utilization (HCRU) and costs between patients with type 2 diabetes mellitus (T2DM) who died from a cardiovascular disease (CVD)-related cause in the year preceding death vs. those who did not die during this same period. METHODS: A large US administrative claims database was used to identify patients with T2DM who died of a CVD-related cause from July 2012 to April 2015. These patients were matched 1:1 to patients with T2DM who did not die, using direct matching methods. HCRU and costs were assessed in each of the four quarters (Q4: 12-10 months; Q3: 9-7 months; Q2: 6-4 months; and Q1: 3-0 months) prior to death and compared between patient cohorts using paired t-tests and McNemar's tests. RESULTS: A final matched cohort of 7648 patients who died and 7648 patients who did not die were identified. A significantly higher proportion of patients who died utilized inpatient services vs. those who did not die (Q4: 12.6% vs. 4.6%, p < .001; Q3: 14.6% vs. 4.6%, p < .001; Q2: 17.6% vs. 5.5%, p < .001; and Q1: 65.0% vs. 10.1%, p < .001). In addition, patients who died incurred significantly higher all-cause costs (Q4: $8882 vs. $3970, p < .001; Q3: $10,462 vs. $3661, p < .001; Q2: $12,564 vs. $4169, p < .001; and Q1: $36,076 vs. $6319, p < .001). CONCLUSIONS: T2DM patients with a CVD-related death had significantly greater HCRU and costs in the year including and preceding death compared to those who did not die.