Effectiveness and Safety of Retreatment with 177Lu-DOTATATE in Patients with Progressive Neuroendocrine Tumors: A Retrospective Real-World Study in the United States.

Advanced neuroendocrine tumors (NETs) are associated with a poor prognosis. A regimen of 4 cycles of 177Lu-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients with advanced NETs. To the best of our knowledge, this is the first study in the United States to evaluate the effectiveness and safety of additional cycles of 177Lu-DOTATATE therapy in patients with progressive NETs. Methods: This was a retrospective chart review of adults with advanced NETs. The patients had undergone initial treatment with up to 4 cycles of 177Lu-DOTATATE and, after disease progression and a period of at least 6 mo since the end of the initial treatment, were retreated with at least 1 additional cycle at a single center (2010-2020). Patient characteristics, treatment patterns, and clinical outcomes were evaluated descriptively. Response was evaluated according to RECIST 1.1; toxicity was defined using criteria from Common Terminology Criteria for Adverse Events, version 5.0. Kaplan-Meier plots were used to evaluate PFS and OS. Results: Of the 31 patients who received 177Lu-DOTATATE retreatment, 61% were male and 94% were White. Overall, patients received a median of 6 cycles (4 initial cycles and 2 retreatment cycles), and the mean administered activity was 41.9 GBq. Two patients also went on to receive additional retreatment (1 and 2 cycles, individually) after a second period of at least 6 mo and progression after retreatment. Best responses of partial response and stable disease were observed in 35% and 65% of patients after the initial treatment and 23% and 45% of patients after retreatment, respectively. The median PFS after the initial treatment was 20.2 mo and after retreatment was 9.6 mo. The median OS after the initial treatment was 42.6 mo and after retreatment was 12.6 mo. Hematologic parameters decreased significantly during both the initial treatment and retreatment but recovered such that there was little difference between the values before the initial treatment and before the retreatment. Clinically significant hematotoxicity occurred in 1 and 3 patients after the initial treatment and retreatment, respectively. No grade 3 or 4 nephrotoxicity was observed. Conclusion: Retreatment with 177Lu-DOTATATE after progression appeared to be well tolerated and offered disease control in patients with progressive NETs after initial 177Lu-DOTATATE treatment.

Real-world outcomes of different lines and sequences of treatment in BRAF-positive advanced melanoma patients.

The objective of this study is to compare efficacy with different treatment sequences and lines of treatment among BRAF V600 mutated (BRAF+) advanced melanoma patients with immunotherapies (IO) and targeted therapies (TT) using real-world data. This was a retrospective cohort study using the Novartis BRAF+ meLanoma patients ObsErvational database, the harmonized customized data from Flatiron and ConcertAI. The study included BRAF+ advanced unresectable melanoma patients treated with first-line (1L) IO or TT between 1 January 2014 and 31 May 2020. Patient characteristics and treatment patterns were described. Kaplan-Meier curves and propensity score-adjusted Cox models were used for analyzing progression-free survival (PFS) and overall survival (OS). A total of 1961 patients were included, of which, 57.2% received IO and 42.8% received TT on 1L therapy. Overall, 603 patients initiated a 2L therapy: 56.2% IO and 43.8% TT. Regardless of treatment sequence, patients progressed at a relatively similar rate with no significant difference between groups (median PFS: 12.9 months for 1L TT/2L IO and 13.1 months for 1L IO/2L TT; HR, 0.84; P = 0.137). The 2-year OS rate was also similar with 1L TT/2L IO and 1L IO/2L TT (78% vs. 80%; HR, 1.09; P = 0.730). PFS was worse on 2L therapy compared with 1L (median 4.7 vs. 6.5 months). Efficacy on 2L therapy was poor compared with 1L. Among patients who received 2L therapy, regardless of treatment sequences, outcomes were comparable between 1L TT/2L IO and 1L IO/2L TT in this study that reflects real-world experiences beyond clinical trial selective eligibility criteria.

Risk tolerance in adjuvant and metastatic melanoma settings: a patient perspective study using the threshold technique.

Background: Adverse events (e.g., pyrexia) may affect treatment patterns and adherence. This study explored pyrexia risk tolerance among melanoma patients when treatment benefit is unknown versus known. Materials & methods: US respondents with stage III (n = 100) or stage III unresectable/stage IV melanoma (n = 125) chose between hypothetical melanoma treatments, defined by reoccurrence/progression-free survival and pyrexia risk, one resembling standard-of-care and one resembling dabrafenib + trametinib. Respondents chose first when efficacy was unknown and then when efficacy was known; pyrexia risk was varied systematically to define maximum acceptable risk. Results: Maximum acceptable risk of pyrexia was statistically significantly higher when efficacy was known versus unknown in stage III patients (85 vs 34%) and stage III unresectable/stage IV patients (66 vs 57%). Conclusion: Patients accepted higher levels of pyrexia risk when they understood treatment benefit.

Adherence to Blood Cholesterol Treatment Guidelines Among Physicians Managing Patients With Atherosclerotic Cardiovascular Disease.

The ACC/AHA blood cholesterol treatment guidelines recommend statin therapy for all patients after experiencing an acute cardiovascular event. Previous analyses have shown that physicians have been slow to adopt guidelines, and many patients remain untreated or undertreated with statins after a cardiovascular event. However, reasons for this remain unknown. This analysis used electronic medical records and patient chart data from Reliant Medical Group (Worcester, Massachusetts) to evaluate physician adherence to the 2013 ACC/AHA blood cholesterol guidelines when treating patients with evidence of acute atherosclerotic cardiovascular disease and the reasons for the observed treatment decisions. Less than 50% of acute atherosclerotic cardiovascular disease patients were treated according to the ACC/AHA guidelines. Nearly 42% of patients not treated according to guidelines received a lower statin intensity than recommended. The most common reason cited by 41.8% of physicians for treating with a statin intensity below the recommended intensity was low-density lipoprotein cholesterol stable or at goal, despite ACC/AHA guidelines recommending specific statin intensities rather than specific low-density lipoprotein cholesterol levels. In conclusion, physician and patient education on the importance of maximizing lipid-lowering therapy in this high-risk patient population should be emphasized.

Treatment patterns and patient characteristics among early initiators of PCSK9 inhibitors.

PURPOSE: To describe patient characteristics and treatment patterns among early initiators of proprotein convertase subtilisin/kexin type nine inhibitors (PCSK9is) who initiated treatment within the first 6 months of market availability. PATIENTS AND METHODS: This retrospective cohort study used IQVIA's longitudinal open-source point-of-sale pharmacy claims database (LRx) and PharMetrics Plus (P+) health plan claims database to identify patients initiating a PCSK9i between January 1, 2016 and June 30, 2016. The index date was defined as the date of the first PCSK9i prescription (index claim) during the enrollment window; patients were followed for ≥6 months postindex. Patient characteristics including use of baseline lipid-lowering therapy (LLT) and measures such as persistence and adherence to PCSK9i therapy were evaluated with respect to health plan type (commercial vs Medicare). RESULTS: Overall, patients initiating PCSK9i (n=13,151) had a mean age of 66 years, and 51% were male. Approximately 67.4% of patients used some form of LLT (statin and/or ezetimibe) in the 24 months prior to initiating PCSK9i therapy. The proportion of patients covered by a commercial health plan (51.2%) was similar to that covered by Medicare (48.8%). Persistence on PCSK9i was marginally longer for patients with commercial insurance than Medicare (mean days on therapy 202.2 vs 198.5). Overall, 42.6% of patients discontinued their PCSK9i during the 180 days of follow-up. CONCLUSION: This study demonstrates that a large proportion of patients discontinue PCSK9i therapy at 30 and 90 days, which are the time frames for which many health plans require recertification to continue access to PCSK9i. Future studies looking at treatment patterns among patients who initiate PCSK9i therapy after the first 180 days once health plan formularies and utilization management criteria were finalized are needed to understand more comprehensively real-world PCSK9i usage patterns.

Low-density lipoprotein cholesterol outcomes post-non-PCSK9i lipid-lowering therapies in atherosclerotic cardiovascular disease and probable heterozygous familial hypercholesterolemia patients.

BACKGROUND: This study evaluated the proportion of patients with atherosclerotic cardiovascular disease (ASCVD) and probable heterozygous familial hypercholesterolemia (HeFH) achieving ≥50% reduction in low-density lipoprotein cholesterol (LDL-C) or reaching the LDL-C ≤70 mg/dL threshold, after initiating or modifying statin, and/or ezetimibe therapy. MATERIALS AND METHODS: Adult ASCVD patients with baseline LDL-C >70 mg/dL (index) and a subset of patients with probable HeFH (proxied by LDL-C ≥190 mg/dL) were identified between January 1, 2012, and August 31, 2014, from the IQVIA electronic medical record database. Patients were followed for 12 months pre-index to examine baseline lipid-lowering therapy (LLT) use, and 12 months post index to evaluate treatment modifications and post-treatment LDL-C levels, stratified by type of treatment received and LDL-C levels at baseline. RESULTS: Of the sample of ASCVD patients who initiated treatment post-index (n=111,147), only 7.6% patients achieved a ≥50% reduction from baseline LDL-C and 19.1% of patients reached the LDL-C ≤70 mg/dL threshold. Among treated ASCVD patients who modified therapy post-index (n=75,523), 5.6% achieved a ≥50% reduction in LDL-C, and proportion of patients achieving LDL-C ≤70 mg/dL ranged from 6.9% to 26.7%, depending on the baseline LDL-C levels. Approximately 50% of the untreated probable HeFH patients (n=3,064) initiated LLT; however, the mean (SD) post-treatment LDL-C remained high (136.2 [47.8] mg/dL), with only 4.4% reaching LDL-C ≤70 mg/dL. Of the treated probable HeFH patients (n=1,073), 41.5% modified treatment; 22.1% achieved a ≥50% reduction in LDL-C and 1.1% reached LDL-C ≤70 mg/dL. CONCLUSION: This study found that most patients had suboptimal LDL-C responses after initiating or modifying standard LLT (statin and/or ezetimibe). More frequent and aggressive lipid management, including increasing statin intensity and alternative therapies, may be needed in patients with ASCVD and probable HeFH to reduce their cardiovascular risk.

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.

Characteristics and health care resource use of subjects with COPD in the year before initiating LAMA monotherapy or LAMA+LABA combination therapy: A U.S. database study.

PURPOSE: To characterize subjects with chronic obstructive pulmonary disease (COPD) newly initiated on long-acting muscarinic antagonists (LAMA) or dual LAMA/long-acting ß2-adrenergic agonist (LABA) therapy. DESIGN: This pilot/preliminary analysis was a retrospective crosssectional study of subjects with COPD from the Optum Impact National Managed Care Benchmark Database. METHODOLOGY: Subjects with at least one LAMA prescription in the index period (July 2008-June 2009) were included and stratified by treatment. Data were collected in the year before the index date and included comorbidities, medication use, COPD-related costs, health care resource use, and exacerbations. RESULTS: Of 5,311 eligible subjects, 2,057 initiated LAMA therapy (LAMA cohort) and 191 initiated LAMA+LABA therapy (LAMA+LABA cohort). The Charlson comorbidity index was slightly lower in the LAMA+LABA cohort than the LAMA cohort (mean±SD: 0.63±1.13 vs. 0.66±1.28), but the number of prescriptions was higher (mean±SD: 42.9±23.2 vs. 30.5±27.2). The LAMA+LABA cohort had higher short-acting inhaled ß2 agonist (56.0% vs. 35.7%), oral corticosteroid (37.7% vs. 32.6%), and home oxygen therapy use (14.1% vs. 3.2%) than the LAMA cohort. Total medical costs were greater in the LAMA+LABA cohort than the LAMA cohort (mean±SD: $3,320.40±4085.9 vs. $1,226.20±3602.9), although emergency department ($11.00±66.8 vs. $30.70±259.2) and outpatient visit ($39.60±163.1 vs. $41.70±424.3) costs were lower. Resource use and exacerbation incidence were similar between cohorts. CONCLUSION: In this first look, subjects with COPD initiating LAMA or LAMA+LABA therapy exhibited different clinical and resource use characteristics in the year before treatment. Subjects receiving LAMA+LABA were older, with higher COPD co-medication use, more prescriptions, and associated higher pharmacy costs compared with subjects initiating LAMA. These differences may reflect a higher severity of COPD in those starting LABA+LAMA treatment.

Patient Characteristics and Real-World Treatment Patterns Among Early Users of PCSK9 Inhibitors.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce low-density lipoprotein cholesterol (LDL-C) levels and are approved for patients with familial hypercholesterolemia or atherosclerotic cardiovascular disease who require additional LDL-C lowering. OBJECTIVE: Our objective was to characterize patients receiving PCSK9i medications in real-world practice and describe physician-reported treatment patterns among dyslipidemia patients using PCSK9i or other lipid-lowering therapy. METHODS: We analyzed data from a point-in-time Adelphi dyslipidemia disease-specific programme (DSP) survey conducted in the USA in 2016. Physicians provided treatment history, laboratory values, patient characteristics, and comorbidities for treated patients. To ensure sufficient numbers of PCSK9i-treated patients, we conducted systematic oversampling of patients being prescribed PCSK9i. Outcomes included patient characteristics and physician-reported treatment patterns. RESULTS: The DSP included 159 physicians, who provided information on 1522 patients (304 PCSK9i; 1218 non-PCSK9i). Mean ± standard deviation (SD) baseline LDL-C levels were 180.0 ± 39.7 mg/dl for PCSK9i patients and 159.2 ± 40.5 mg/dl for non-PCSK9i patients. Prior statin use was reported in 69.1% of PCSK9i patients and 19.5% of non-PCSK9i patients, and physician-reported statin intolerance was observed in 31.6% of PCSK9i and 5.3% of non-PCSK9i patients. Use of statins only was reported in 40.5% of PCSK9i and 88.8% of non-PCSK9i patients. The most common physician-reported reasons for change to PCSK9i were lack of efficacy (70.2%) and muscle-related symptoms (myalgia 28.6%; myopathy 11.1%). CONCLUSIONS: Physicians surveyed appeared to prescribe PCSK9i medications appropriately. PCSK9i-treated patients had higher rates of cardiovascular comorbidities and physician-determined statin intolerance, had higher LDL-C levels, and received more lines of therapy than non-PCSK9i patients.

Ezetimibe Use and LDL-C Goal Achievement: A Retrospective Database Analysis of Patients with Clinical Atherosclerotic Cardiovascular Disease or Probable Heterozygous Familial Hypercholesterolemia.

BACKGROUND: Ezetimibe is recommended by clinical practice guidelines as a second-line therapy for lowering low-density lipoprotein cholesterol (LDL-C) levels, but little is known about its use and effectiveness in real-world populations. OBJECTIVE: To understand the real-world impact of adding or switching to ezetimibe on LDL-C goal achievement in patients with clinical atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH). METHODS: Patients aged ≥ 18 years with an LDL-C measurement available between January 1, 2013, and June 30, 2014, were identified using the Inovalon MORE 2 database; this included commercial, health insurance exchange, Medicare Advantage, and managed Medicaid patients. The index date was the date of the first LDL-C measurement. Patients were required to have evidence of clinical ASCVD or probable HeFH based on ICD-9-CM codes and ≥ 1 outpatient pharmacy claim for a statin in the 1-year pre-index period, as well as continuous medical and pharmacy coverage for 1 year pre- and post-index. Patients who added ezetimibe to existing statin therapy or switched to ezetimibe within 90 days post-index LDL-C measurement were identified in order to replicate the typical time a clinician takes to assess the use of ezetimibe. The primary outcome was the proportion of patients who met the LDL-C goal of < 70 mg/dL within the follow-up period. LDL-C goal achievement was evaluated by baseline LDL-C level groupings: < 70 mg/dL, 70-99 mg/dL, 100-129 mg/dL, or ≥ 130 mg/dL; and across 4 patient diagnosis categories: all patients, ASCVD only, probable HeFH only, and ASCVD and probable HeFH. Descriptive analyses were reported. Categorical variables were summarized as the number of and corresponding percentage of patients. Continuous variables were presented as the mean and SD of the number of observations and median and range where appropriate. RESULTS: Of 125,330 patients who met selection criteria, mean age was 70.1 (SD = 9.9) years and mean LDL-C baseline was 90.7 (SD = 34.0) mg/dL. Over one half of patients (70%) were receiving statin therapy. Within the post-index time frame, 1.05% (n = 1,309) of patients added or switched to ezetimibe. Of these, 26% achieved LDL-C goal during the 90-day follow-up (59.5% did not achieve goal and 14.4% did not have a follow-up lab value). Therapeutic targets were reached by 30% of patients with baseline LDL-C levels of 70-99 mg/dL; 14% of those with baseline LDL-C of 100-129 mg/dL; and 7% of those with baseline LDL-C of ≥ 130 mg/dL. Achievement of LDL-C goals also varied by baseline diagnosis category. CONCLUSIONS: The addition of or switch to ezetimibe therapy was associated with a relatively small percentage of LDL-C goal achievement (< 70 mg/dL) in patients with clinical ASCVD and/or HeFH, even among patients with baseline LDL-C between 70 and 99 mg/dL. To provide superior individualized care for patients with hyperlipidemia, there is a potential role for newer therapies in lipid lowering, such as PCSK9 inhibitors, in appropriate high-risk populations. DISCLOSURES: This study was sponsored by Amgen. Menzin, Yu, and Stern are employees of Boston Health Economics, which was contracted by Amgen to perform this study. Aggarwal is a former employee of Boston Health Economics. Boatman, Patel, and Harrison are employees and stockholders of Amgen. Study concept and design were contributed by Menzin, Aggarwal, Harrison, and Patel. Aggarwal, Stern, and Yu collected the data. Data interpretation was performed by Aggarwal, Harrison, Patel, and Boatman. The manuscript was written and revised primarily by Aggarwal, with assistance from the other authors.

Estimation of Missed Statin Prescription Use in an Administrative Claims Dataset.

BACKGROUND: Nonadherence to statin medications is associated with increased risk of cardiovascular disease and poses a challenge to lipid management in patients who are at risk for atherosclerotic cardiovascular disease. Numerous studies have examined statin adherence based on administrative claims data; however, these data may underestimate statin use in patients who participate in generic drug discount programs or who have alternative coverage. OBJECTIVE: To estimate the proportion of patients with missing statin claims in a claims database and determine how missing claims affect commonly used utilization metrics. METHODS: This retrospective cohort study used pharmacy data from the PharMetrics Plus (P+) claims dataset linked to the IMS longitudinal pharmacy point-of-sale prescription database (LRx) from January 1, 2012, through December 31, 2014. Eligible patients were represented in the P+ and LRx datasets, had ≥1 claim for a statin (index claim) in either database, and had ≥ 24 months of continuous enrollment in P+. Patients were linked between P+ and LRx using a deterministic method. Duplicate claims between LRx and P+ were removed to produce a new dataset comprised of P+ claims augmented with LRx claims. Statin use was then compared between P+ and the augmented P+ dataset. Utilization metrics that were evaluated included percentage of patients with ≥ 1 missing statin claim over 12 months in P+; the number of patients misclassified as new users in P+; the number of patients misclassified as nonstatin users in P+; the change in 12-month medication possession ratio (MPR) and proportion of days covered (PDC) in P+; the comparison between P+ and LRx of classifications of statin treatment patterns (statin intensity and patients with treatment modifications); and the payment status for missing statin claims. RESULTS: Data from 965,785 patients with statin claims in P+ were analyzed (mean age 56.6 years; 57% male). In P+, 20.1% had ≥ 1 missing statin claim post-index; 13.7% were misclassified as nonstatin users; and 14.9% were misclassified as new statin users. MPR was higher in the augmented P+ dataset versus the P+ dataset alone for all patients (79.4% vs. 76.7%, P < 0.001) and new users (61.4% vs. 58.7%, P < 0.001). Similarly, mean PDC was higher in the P+ dataset augmented with LRx versus the P+ dataset alone for all patients (76.0% vs. 74.0%, P < 0.001) and new users (58.5% vs. 56.5%, P < 0.001). Most patients received moderate-intensity statins; few changes in dose, intensity, or discontinuation of statins were observed when the P+ dataset was augmented. The most common reasons for missing data were payment by an alternate third-party program (66.3%) and use of cash, coupon, or discount cards (18.7%). CONCLUSIONS: Augmenting commercial claims data with point-of-sale data provides a more accurate assessment of statin use than claims data alone. DISCLOSURES: This study was funded by Amgen, which contributed to data interpretation and manuscript preparation. Wade, Hill, and De are employees of QuintilesIMS, which received funding from Amgen for work on this study. Patel and Harrison are employees of Amgen and own Amgen stock/stock options. Study concept and design were contributed by Wade, Hill, Patel, and Harrison. De took the lead in data collection, along with the other authors, and all authors contributed to data analysis. The manuscript was written and revised by all the authors.

Clinical and economic burden of dyspnea and other COPD symptoms in a managed care setting.

PURPOSE: The degree to which symptoms such as dyspnea affect patients with COPD is individualized. To address the gap between clinical symptom measures and self-perceived disease burden, we investigated the symptom status of adult patients with COPD and followed with an administrative claims analysis of health care resource utilization and costs. METHODS: This was a hybrid US observational study consisting of a cross-sectional patient survey followed by a retrospective analysis of administrative claims data. The primary COPD symptom measures were the modified Medical Research Council (mMRC) Dyspnea scale and the COPD Assessment Test (CAT). RESULTS: A total of 673 patients completed the survey. Of these, 65% reported mMRC grades 0-1 (low symptomatology) and 35% reported mMRC grades 2-4 (high symptomatology); 25% reported CAT score <10 (low symptomatology) and 75% reported CAT score ≥10 (high symptomatology). More patients with high symptomatology (by either measure) had at least one COPD-related inpatient hospitalization, emergency room visit, physician office visit, or other outpatient services, and filled at least one COPD-related prescription medication vs patients with low symptomatology. COPD-related costs were higher for patients with high symptomatology than patients with low symptomatology. In a multivariate analysis, COPD-related costs were also higher in patients reporting severe symptoms. CONCLUSION: Patients with high COPD symptomatology utilized more health care resources and had higher COPD-related health care costs during the 6-month post-survey period than patients with low symptomatology.

A retrospective study to assess clinical characteristics and time to initiation of open-triple therapy among patients with chronic obstructive pulmonary disease, newly established on long-acting mono- or combination therapy.

INTRODUCTION: An incremental approach using open-triple therapy may improve outcomes in patients with chronic obstructive pulmonary disease (COPD). However, there is little sufficient, real-world evidence available identifying time to open-triple initiation. METHODS: This retrospective study of patients with COPD, newly initiated on long-acting muscarinic antagonist (LAMA) monotherapy or inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) combination therapy, assessed baseline demographics, clinical characteristics, and exacerbations during 12 months prior to first LAMA or ICS/LABA use. Time to initiation of open-triple therapy was assessed for 12 months post-index date. Post hoc analyses were performed to assess the subsets of patients with pulmonary-function test (PFT) information and patients with and without comorbid asthma. RESULTS: Demographics and clinical characteristics were similar between cohorts in the pre-specified and post hoc analyses. In total, 283 (19.3%) and 160 (10.9%) patients had moderate and severe exacerbations at baseline, respectively, in the LAMA cohort, compared with 482 (21.3%) and 289 (12.8%) patients in the ICS/LABA cohort. Significantly more patients initiated open-triple therapy in the LAMA cohort compared with the ICS/LABA cohort (226 [15.4%] versus 174 [7.7%]; P<0.001); results were similar in the post hoc analyses. Mean (standard deviation) time to open-triple therapy was 79.8 (89.0) days in the LAMA cohort and 122.9 (105.4) days in the ICS/LABA cohort (P<0.001). This trend was also observed in the post hoc analyses, though the difference between cohorts was nonsignificant in the subset of patients with PFT information. DISCUSSION: In this population, patients with COPD are more likely to initiate open-triple therapy following LAMA therapy, compared with ICS/LABA therapy. Further research is required to identify factors associated with the need for treatment augmentation among patients with COPD.

Cost-effectiveness analysis of umeclidinium/vilanterol for the management of patients with moderate to very severe COPD using an economic model.

BACKGROUND: Bronchodilators such as long-acting muscarinic antagonists (LAMAs) and long-acting ß2-agonists (LABAs) are central to the pharmacological management of COPD. Dual bronchodilation with umeclidinium/vilanterol (UMEC/VI; 62.5/25 µg) is a novel LAMA/LABA combination approved for maintenance treatment for patients with COPD. OBJECTIVE: The objective of this study was to assess the cost-effectiveness of maintenance treatment with UMEC/VI compared with tiotropium (TIO) 18 µg, open dual LAMA + LABA treatment, or no long-acting bronchodilator treatment in patients with moderate to very severe COPD. METHODS: A Markov model was developed to estimate the costs and outcomes associated with UMEC/VI treatment in patients with moderate to very severe COPD (GSK study number: HO-13-13411). Clinical efficacy, costs, utilities, and mortality obtained from the published literature were used as the model inputs. Costs are presented in US dollars based on 2015 prices. The model outputs are total costs, drug costs, other medical costs, number of COPD exacerbations, and quality-adjusted life-years (QALYs). Costs and outcomes were discounted at a 3% annual rate. Incremental cost-effectiveness ratios were calculated. One-way and probabilistic sensitivity analyses were conducted to assess the effects of changing parameters on the uncertainty of the results. RESULTS: UMEC/VI treatment for moderate to very severe COPD was associated with lower lifetime medical costs ($82,344) compared with TIO ($88,822), open dual LAMA + LABA treatment ($114,442), and no long-acting bronchodilator ($86,751). Fewer exacerbations were predicted to occur with UMEC/VI treatment compared with no long-acting bronchodilator treatment. UMEC/VI provided an 0.11 and 0.25 increase in QALYs compared with TIO and no long-acting bronchodilator treatment, and as such, dominated these cost-effectiveness analyses. Sensitivity analyses confirmed that the results were robust. CONCLUSION: The results from this model suggest that UMEC/VI treatment would be dominant compared with TIO and no long-acting bronchodilator treatment, and less costly than open dual LAMA + LABA treatment in patients with moderate to very severe COPD.

Effect of 2013 ACC/AHA Blood Cholesterol Guidelines on Statin Treatment Patterns and Low-Density Lipoprotein Cholesterol in Atherosclerotic Cardiovascular Disease Patients.

BACKGROUND: Preceding release of the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol guidelines, prescribers aimed for specific low-density lipoprotein cholesterol (LDL-C) goals in patients with atherosclerotic cardiovascular disease (ASCVD). The 2013 guidelines changed this focus to treating patients with appropriate statin intensity given their ASCVD risk. We examined statin use and LDL-C levels before and after the 2013 ACC/AHA guidelines in patients with clinical ASCVD as defined in the guidelines. METHODS AND RESULTS: We conducted a retrospective cohort study of adult commercial and Medicare Advantage health plan enrollees in the Optum Research Database. Patients had ≥1 claim with a diagnosis of clinical ASCVD between November 1, 2012 and December 31, 2014 and were continuously enrolled 6 months before (baseline) and 7 months after (follow-up) the first ASCVD visit. Patients were assigned to monthly cohorts based on ASCVD event month. Statin use and intensity were measured at baseline and first month of follow-up. LDL-C changes were assessed using ordinary least squares regression. For 90 287 patients, mean (SD) age was 68 (12) years; 50% were female; and 30% had commercial insurance. Statin use remained consistent before and after guidelines (32% and 31%, respectively). Of patients receiving statins, high-intensity use increased by 4 percentage points 1 year after guidelines (P<0.001). Mean LDL-C levels were 2.4 mmol/L (94 mg/dL) both pre- and postguidelines. CONCLUSIONS: Statin use and mean monthly LDL-C before and after the guidelines remained largely unchanged; statin intensity increased modestly. More effort may be needed to increase guideline understanding and adherence to improve treatment of high-risk patients.

Longitudinal Treatment Patterns and Associated Outcomes in Patients With Newly Diagnosed Systemic Lupus Erythematosus.

PURPOSE: The treatment of systemic lupus erythematosus (SLE) is complex, with a wide range of drugs commonly prescribed. The aims of this study were to identify longitudinal treatment patterns in patients with incident SLE and to estimate the associations of treatment patterns with clinical and economic outcomes. METHODS: This retrospective, observational cohort study used a US managed care claims database to identify patients with newly diagnosed SLE and 4-year treatment follow-up. Patients were aged ≥ 18 years, with continuous medical and pharmacy benefits for 12 months before and 48 months after the index date (first medical claim with a diagnosis of SLE). Longitudinal treatment patterns were grouped using a k-means cluster analysis. Therapies were included in the cluster analysis if the mean number of prescriptions in each year was ≥ 0.05. Clinical and economic outcomes were compared across clusters using multivariate regression analyses. FINDINGS: Data from 1611 patients with incident SLE were analyzed (91.4% women; mean [SD] age, 44.5 [9.5] years; 56.2% managed primarily by a specialist). Hydroxychloroquine and corticosteroids were the most commonly prescribed therapies; methotrexate, azathioprine, and mycophenolate mofetil also met the criteria for inclusion in the cluster analysis. Ten treatment clusters were identified; the most common was minimally treated patients (42.8%). Hydroxychloroquine monotherapy, corticosteroid monotherapy, and corticosteroid/hydroxychloroquine combination therapy were received by 34.0%, 11.2%, and 7.8% of patients, respectively. Methotrexate or azathioprine with a corticosteroid/hydroxychloroquine were received by 4.2% of patients. Changes in therapy, except discontinuations, were rare. Compared with the minimally treated cluster, those that received corticosteroid monotherapy (mean dose, >12.0 mg/d) had poorer clinical and economic outcomes; the hydroxychloroquine-monotherapy cluster had similar or better outcomes; and patients who received a corticosteroid/hydroxychloroquine with or without methotrexate or azathioprine demonstrated outcomes that were poorer but that appeared better than those with corticosteroid monotherapy. SLE-related visits with a nonspecialist were common (~45%) and remained unchanged over time despite better clinical and economic outcomes associated with specialist visits. IMPLICATIONS: This study utilized cluster analysis, an unsupervised machine-learning method, to systematically discern treatment patterns over 4 years and to estimate outcomes associated with the identified treatment patterns. The results suggest that minimal treatment is the most common approach in patients with newly diagnosed SLE. Clinical and economic outcomes are poorest with corticosteroid monotherapy but may improve with the addition of hydroxychloroquine and/or an immunosuppressive agent. A large proportion of SLE care is provided by nonspecialists despite the potential benefits of involving a specialist.

A Retrospective Administrative Claims Database Evaluation of the Utilization of Belimumab in US Managed Care Settings.

PURPOSE: Belimumab is an approved therapy for the treatment of systemic lupus erythematosus (SLE). This study examined the real-world utilization patterns of belimumab and standard SLE therapies in patients after regulatory approval of belimumab in the United States. METHODS: A retrospective, observational study of belimumab users in the HealthCore Integrated Research Database was conducted using administrative claims data (GlaxoSmithKline Clinical Study Register Study ID: 114955). The overall population for analysis was composed of patients who were prescribed belimumab, had ≥6 months pre- and ≥6 months post-index medical and pharmacy eligibility, and at least 1 medical claim for SLE. Patients' clinical and demographic characteristics, treatment history, treatment patterns of belimumab, utilization of other medications, all-cause resource utilization, and costs were assessed. No hypotheses were tested. FINDINGS: All patients who were prescribed belimumab had an SLE claim. Patients who met all eligibility criteria (n = 155) were primarily female (94.2%; mean [SD] age, 44 [12] years) and 94.2% had used standard SLE therapies during the pre- and post-index periods. The majority had moderate SLE disease severity pre-index, and there was a small shift (approximately 8%) from moderate to mild SLE after initiation of belimumab. Two thirds of patients remained on belimumab therapy at 6 months post-index. The percentage of patients with any claim for oral corticosteroids remained stable; however, the point estimate for mean daily dose decreased slightly in months 3 to 6 post-index. Inpatient hospital admissions decreased slightly in the post-index period. The point estimate for total costs (excluding belimumab) decreased after initiation of belimumab, although overall total health care costs (including belimumab) increased. IMPLICATIONS: All patients with a belimumab prescription had an SLE diagnosis on at least 1 medical claim, and the vast majority of those meeting all eligibility criteria had previously used a standard SLE therapy. Disease severity improved for a number of patients while on belimumab treatment and modest corticosteroid dose reductions were observed in later months. After initiating belimumab, health care costs (excluding belimumab) decreased. GlaxoSmithKline Clinical Study Register Study ID: 114955.

Impact of COPD Exacerbation Frequency on Costs for a Managed Care Population.

BACKGROUND: There is scarce information on chronic obstructive pulmonary disease (COPD) outcomes and costs for patients with differing levels of COPD exacerbations. OBJECTIVE: To examine COPD-related and all-cause health care resource use and costs in subsequent years for frequently and infrequently exacerbating COPD patients. METHODS: Patients with a diagnosis of COPD (ICD-9-CM codes 491.xx, 492.xx, and 496.xx) were identified (1 hospitalization or 1 emergency department visit or at least 2 outpatient visits) using administrative claims data in 2007. Patients were classified in 2008 as frequent (at least 2 exacerbations/year), infrequent (1 exacerbation/year) and nonexacerbators. Outcomes were computed during a subsequent 2-year period (2009 and 2010). Average per person estimates and total sample-level estimates were calculated. A logistic regression model estimated the predictors of having 2 or more exacerbations per year during the follow-up period. RESULTS: 61,750 COPD patients met the study criteria (mean age 67 years). Of these, 6% (n = 3,852) were frequent exacerbators; 14% were infrequent exacerbators (n = 8,416); and 80% were nonexacerbators (n = 49,482). At baseline, average all-cause health care costs per patient for frequent exacerbators were highest followed by infrequent and nonexacerbators ($12,837, $10,480, and $7,756, respectively). On average, 60% of frequent and 40% of infrequent exacerbators had at least 1 exacerbation per year in follow-up. Average annual per patient COPD-related costs for frequent exacerbators ($3,565 in 2009 and $3,528 in 2010) were more than 3 times (P less than 0.05) and infrequent exacerbators ($2,264 in 2009 and $2,265 in 2010) were more than 2 times (P less than 0.05) higher compared with nonexacerbators ($1,007 in 2009 and $1,027 in 2010). On a total sample-level, infrequent exacerbators were similar if not more burdensome compared with frequent exacerbators in the proportion accounted by these cohorts for total COPD-related costs (23% vs. 18%, respectively) and total number of COPD exacerbations per year (26% vs. 26%). Compared with nonexacerbators, infrequent exacerbators were 3 times (OR = 2.8, P less than 0.001) significantly more likely to have 2 or more exacerbations per year in follow-up, and frequent exacerbators were 7 times (OR = 6.76, P less than 0.001) significantly more likely to have 2 or more exacerbations per year in follow-up. CONCLUSIONS: Infrequent exacerbators have an increased risk for future exacerbations compared with nonexacerbators and, on a total sample-level, incur greater costs compared with frequent exacerbators, demonstrating a significant economic burden.

Indirect costs in chronic obstructive pulmonary disease: a review of the economic burden on employers and individuals in the United States.

OBJECTIVE: To review and summarize existing literature on the indirect burden of chronic obstructive pulmonary disease (COPD) in the US. METHODS: Medline, Scopus, and OvidSP databases were searched using defined search terms to identify relevant studies. Eligible studies were published in English between January 2000 and April 2012 and calculated the indirect burden of COPD in a US population in terms of prevalence, incidence or costs of productivity loss, disability, morbidity, or mortality. RESULTS: Of 53 studies identified, eleven met eligibility criteria, with data years spanning 1987-2009. Estimates of workforce participation range from 56% to 69% among individuals with COPD and from 65% to 77% among individuals without COPD. Approximately 13%-18% of those with COPD are limited in the amount or type of work they can do and one-third or more experience general activity limitation. Estimates of restricted activity days range from 27-63 days per year. Estimates of mean annual sick leave and/or disability days among employed individuals with COPD range from 1.3-19.4 days. Estimates of bed confinement range from 13-32 days per year. Estimated mean annual indirect costs were $893-$2,234/person (US dollars) with COPD ($1,521-$3,348 in 2010 [US dollars]) and varied with the population studied, specific cost outcomes, and economic inputs. In studies that assessed total (direct and indirect) costs, indirect costs accounted for 27%-61% of total costs, depending on the population studied. CONCLUSIONS: COPD is associated with substantial indirect costs. The disease places a burden on employers in terms of lost productivity and associated costs and on individuals in terms of lost income related to absenteeism, activity limitation, and disability. Consideration of indirect as well as direct costs is necessary to gain a more complete view of the societal burden of COPD.

Differences in obesity management among physicians.

Despite the strong recommendations of guidelines, intensive obesity management is not offered to all obese patients. This study aimed to examine differences in obesity management between primary care physicians (PCPs) and non-PCPs. A cross-sectional study was performed using the 2006-2007 National Ambulatory Medical Care Survey. Adults (age ≥20 years) with obesity (body mass index (BMI)≥30 kg/m(2) or obesity diagnosis using International Classification of Diseases, Ninth Revision, Clinical Modification code 278) were included in the study cohort. A multivariate logistic regression model was constructed to examine differences between PCPs and non-PCPs (primary independent variable) for obesity management (dependent variable) while controlling for predisposing, enabling, and need characteristics per Anderson's behavioral model. In all, 32.66% of 214 million visits by obese patients in 2006-2007 resulted in obesity management. PCPs were 2.38 times more likely to provide obesity management compared to non-PCPs (odds ratio [OR]=2.37; 95% confidence interval [CI]: 1.69, 3.36). Patients who had preventive visits (OR=2.23; 95% CI: 1.50, 3.32) and chronic visits (OR=1.93; 95% CI: 1.46, 2.55) were more likely to receive obesity management than patients who had acute visits. More time spent with physician, more comorbid conditions, and BMI ≥ 40 significantly increased the likelihood of receiving obesity management, while older age and smoking reduced the likelihood of receiving obesity management. Only one third of ambulatory care visits in 2006-2007 resulted in obesity management. A difference in obesity management was noted between PCPs and non-PCPs. Future research should aim to identify the reasons for these observed differences, ensure equitable access, and address the undertreatment of obesity.