The impact of serum lipids on risk for microangiopathy in patients with type 2 diabetes mellitus.

BACKGROUND: Few large-scale, real-world studies have assessed the relative associations of lipid fractions with diabetic microvascular events. The main objective of this study was to evaluate the association of the lipid profile components, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), and non-high density lipoprotein cholesterol (non-HDL-C) with microvascular complications (MVCs) in type 2 diabetes mellitus (T2DM) patients. METHODS: This observational cohort study queried the HealthCore Integrated Research Database (HIRDSM) for newly-diagnosed (Index Date) 18-64-year-old patients with diabetes mellitus between 01/01/2005-06/30/2010. Inclusion required ≥ 12 months pre-index continuous health plan eligibility and ≥ 1 pre-index lipid profile result. Patients with polycystic ovary syndrome and prior MVCs were excluded. Incident complications were defined as the earliest occurrence of diabetic retinopathy, peripheral neuropathy, and/or nephropathy post-index. Cox proportional models and Kaplan-Meier (KM) curves were used to evaluate associations among variables. RESULTS: Of the patients (N=72,267), 50.05% achieved HDL-C, 64.28% LDL-C, 59.82% TG, and 56.79% non-HDL-C American Diabetes Association goals at baseline. During follow-up (mean, 21.74 months), there were 5.21 microvascular events per 1,000 patient-months. A 1-mg/dL increase in HDL-C was associated with 1% decrease in any MVC risk (P< .0001), but for LDL-C, TG, and non-HDL-C, 1-mg/dL increase resulted in increases of 0.2% (P< .0001), 0.1% (P<0.001) and 0.3% (P<0.001) in MVC risk. Patients achieving HDL-C goals had a 11% lower risk of MVC versus non-achievers (RR 0.895, [95% CI, 0.852-0.941], P< .0001). Similarly, TG goal attainment was associated with a lowered risk for any MVC (RR 0.849, [95% CI, 0.808-0.892], P< .0001). Evaluation of KM survival curves demonstrated no significant difference in the risk of MVCs between patients achieving vs. not achieving LDL-C goals, but did demonstrate a difference in MVC risk between patients achieving vs. not achieving non-HDL-C goals. CONCLUSION: This study demonstrates significant independent associations among lipid fractions and risk for microangiopathy. These findings suggest that attaining established ADA goals for HDL-C, TG, and non-HDL-C may reduce risk for microvascular events among patients with diabetes.

Effect of V-Go Versus Multiple Daily Injections on Glycemic Control, Insulin Use, and Diabetes Medication Costs Among Individuals with Type 2 Diabetes Mellitus.

BACKGROUND: Coping with discomfort and the uncertainties of daily adjustments are prominent challenges confronting individuals with type 2 diabetes mellitus (T2DM) who require multiple daily injections (MDI) of insulin. For this growing population, wearable, disposable devices capable of delivering consistent and sustained doses of basal-bolus therapy may help to alleviate concerns and improve outcomes. However, studies on the comparative effectiveness of new, innovative delivery systems versus MDI on insulin requirements, glycemic control, and health care costs are sparse. OBJECTIVE: To examine glycemic control, insulin use, and diabetes medication costs for users of the V-Go Wearable Insulin Delivery device compared with MDI insulin therapy among individuals with T2DM in a commercially insured population in the United States. METHODS: This retrospective cohort study queried administrative claims data from the HealthCore Integrated Research Database from July 1, 2011, through July 31, 2017. Cohorts included individuals with T2DM aged 21-80 years either newly initiating V-Go or using MDI for basal/bolus insulin. The date of earliest claim for V-Go prescription fill or for bolus insulin was defined as the index date, depending on the cohort. Previous insulin therapy was required in both cohorts. Baseline hemoglobin A1c (A1c) values were identified during the 6 months before and 15 days after the index date; results closest to 12 months after the index date were selected as follow-up. Insulin use and diabetes medication cost data were examined during the 6 months baseline and the second half of the 1-year follow-up. V-Go and MDI users were 1:1 matched on baseline insulin exposure, A1c level, and other characteristics of interest. Univariate and multivariate tests were used to compare follow-up outcomes. RESULTS: Matched cohorts included 118 well-balanced pairs (mean age: 56 years; mean baseline A1c: 9.2%). During follow-up, both cohorts experienced improvements in glycemic control relative to baseline (% with A1c ≤ 9%, baseline/follow-up: V-Go 49/69, P < 0.001; MDI 50/60, P = 0.046). With similar baseline insulin prescription fills and diabetes medication costs, V-Go users required fewer insulin prescription fills (mean change: -0.8 vs. +1.8 fills, P < 0.001; -17% vs. +38%); had a smaller increase in diabetes medication costs (mean change in 2016 USD: $341 vs. $1,628, P = 0.012; +10% vs. +47%); and a decrease in insulin total daily dose (mean change in insulin units per day: -29.2 vs. +5.8, P < 0.001; -21% vs. +4%), compared with MDI users, during the last 6 months of follow-up. CONCLUSIONS: This study was the first to evaluate clinical and economic outcomes associated with the use of V-Go for up to a 1-year follow-up period. Relative to MDI users, V-Go users had similar glycemic control but lower insulin use and lower diabetes medication costs during follow-up. V-Go therapy may provide an opportunity to improve quality measures more cost-effectively in people with T2DM who require basal-bolus therapy. DISCLOSURES: This study was funded by Valeritas. Nguyen is an employee of Valeritas. Zhou, Grabner, Barron, and Quimbo are employees of HealthCore, which received funding for this study from Valeritas. Raval was an employee of HealthCore at the time the study was conducted. Partial findings from this study were presented at the International Society of Pharmacoeconomics and Outcomes Research 23rd Annual International Meeting; May 19-23, 2018; Baltimore, MD; and the 54th European Association for the Study of Diabetes Annual Meeting; October 1-5, 2018; Berlin, Germany.

Effect of V-Go Versus Multiple Daily Injections on Glycemic Control, Insulin Use, and Diabetes Medication Costs Among Individuals with Type 2 Diabetes Mellitus.

BACKGROUND: Coping with discomfort and the uncertainties of daily adjustments are prominent challenges confronting individuals with type 2 diabetes mellitus (T2DM) who require multiple daily injections (MDI) of insulin. For this growing population, wearable, disposable devices capable of delivering consistent and sustained doses of basal-bolus therapy may help to alleviate concerns and improve outcomes. However, studies on the comparative effectiveness of new, innovative delivery systems versus MDI on insulin requirements, glycemic control, and health care costs are sparse. OBJECTIVE: To examine glycemic control, insulin use, and diabetes medication costs for users of the V-Go Wearable Insulin Delivery device compared with MDI insulin therapy among individuals with T2DM in a commercially insured population in the United States. METHODS: This retrospective cohort study queried administrative claims data from the HealthCore Integrated Research Database from July 1, 2011, through July 31, 2017. Cohorts included individuals with T2DM aged 21-80 years either newly initiating V-Go or using MDI for basal/bolus insulin. The date of earliest claim for V-Go prescription fill or for bolus insulin was defined as the index date, depending on the cohort. Previous insulin therapy was required in both cohorts. Baseline hemoglobin A1c (A1c) values were identified during the 6 months before and 15 days after the index date; results closest to 12 months after the index date were selected as follow-up. Insulin use and diabetes medication cost data were examined during the 6 months baseline and the second half of the 1-year follow-up. V-Go and MDI users were 1:1 matched on baseline insulin exposure, A1c level, and other characteristics of interest. Univariate and multivariate tests were used to compare follow-up outcomes. RESULTS: Matched cohorts included 118 well-balanced pairs (mean age: 56 years; mean baseline A1c: 9.2%). During follow-up, both cohorts experienced improvements in glycemic control relative to baseline (% with A1c ≤ 9%, baseline/follow-up: V-Go 49/69, P < 0.001; MDI 50/60, P = 0.046). With similar baseline insulin prescription fills and diabetes medication costs, V-Go users required fewer insulin prescription fills (mean change: -0.8 vs. +1.8 fills, P < 0.001; -17% vs. +38%); had a smaller increase in diabetes medication costs (mean change in 2016 USD: $341 vs. $1,628, P = 0.012; +10% vs. +47%); and a decrease in insulin total daily dose (mean change in insulin units per day: -29.2 vs. +5.8, P < 0.001; -21% vs. +4%), compared with MDI users, during the last 6 months of follow-up. CONCLUSIONS: This study was the first to evaluate clinical and economic outcomes associated with the use of V-Go for up to a 1-year follow-up period. Relative to MDI users, V-Go users had similar glycemic control but lower insulin use and lower diabetes medication costs during follow-up. V-Go therapy may provide an opportunity to improve quality measures more cost-effectively in people with T2DM who require basal-bolus therapy. DISCLOSURES: This study was funded by Valeritas. Nguyen is an employee of Valeritas. Zhou, Grabner, Barron, and Quimbo are employees of HealthCore, which received funding for this study from Valeritas. Raval was an employee of HealthCore at the time the study was conducted. Partial findings from this study were presented at the International Society of Pharmacoeconomics and Outcomes Research 23rd Annual International Meeting; May 19-23, 2018; Baltimore, MD; and the 54th European Association for the Study of Diabetes Annual Meeting; October 1-5, 2018; Berlin, Germany.

Health Plan Enrollment and Disenrollment of Individuals With and Without Established Chronic Disease in a U.S. Commercially Insured and Medicare Advantage Population.

BACKGROUND: Chronic disease is associated with increased health care resource utilization and costs. Effective development and implementation of health care management and clinical intervention programs require an understanding of health plan member enrollment and disenrollment behavior. OBJECTIVE: To examine the health plan enrollment and disenrollment behavior of commercially insured and Medicare Advantage members with established chronic disease compared with matched members without the disease of interest, using data from a large national health insurer in the United States. METHODS: This retrospective matched cohort study used administrative claims data from the HealthCore Integrated Research Database from January 1, 2006, to November 30, 2015, to identify adults with chronic disease (type 2 diabetes mellitus [T2DM], cardiovascular disease [CVD], chronic obstructive pulmonary disease [COPD], rheumatoid arthritis [RA], and breast cancer [BC]). Members with no established chronic disease (controls) were directly matched to members with established chronic disease (cases) on demographic characteristics. The earliest date on which members met the criteria for a given disease was defined as the index date. Controls had the same index date as the matched cases. All members had ≥ 12 months of continuous health plan enrollment before the index date. Outcomes included health plan member disenrollment and enrollment duration. Incidence rates per 1,000 member-years for member disenrollment were evaluated along with incidence rate ratios (relative risk) using a Poisson model. Time to disenrollment was analyzed by Cox proportional hazard models and Kaplan-Meier survival curves. Sensitivity analyses were conducted where death was included as a disenrollment event. RESULTS: 70,907 health plan members with BC (99.7% female, mean age 60.5 years); 28,883 members with COPD (52.3% female, mean age 66.7); 835,358 members with CVD (50.5% female, mean age 62.7 years); 210,936 members with T2DM (45.2% female, mean age 53.6 years); and 31,954 members with RA (72.0% female, mean age 55.5 years) were matched to controls and met the study criteria. The incidence rates of health plan disenrollment ranged from 155 to 192 members per 1,000 members per year. Compared with controls, members with chronic disease were 30%-40% less likely to disenroll from a health plan (P < 0.001 for all comparisons). Among those who disenrolled, enrollment duration ranged from 2.3 to 2.7 years among cases and 1.5 to 1.8 years among matched controls (P ≤ 0.001 for all comparisons). CONCLUSIONS: This real-world study demonstrated that members with chronic disease had a significantly lower rate of disenrollment and a longer duration of enrollment compared with matched controls and were continuously enrolled for almost a year longer than members without a diagnosed chronic disease. Understanding health plan enrollment and disenrollment behavior may provide a valuable context for determining the time frame for the effect of health care programs and initiatives. DISCLOSURES: Funding for this study was provided by HealthCore, a wholly owned subsidiary of Anthem. Chung, Deshpande, Zolotarjova, Quimbo, and Willey are employees of HealthCore. Kern and Cochetti are former employees of HealthCore. Quimbo, Cochetti, and Willey are shareholders of Anthem. HealthCore receives funding from multiple pharmaceutical companies to perform various research studies outside of the submitted work. The preliminary results of this study were presented at AMCP Nexus 2015; March 26-29, 2015; Orlando, FL, and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2017 Conference; May 20-24, 2017; Boston, MA.

Persistence with migraine prophylactic treatment and acute migraine medication utilization in the managed care setting.

OBJECTIVE: The aim of this study was to describe persistence with migraine prophylactic treatment and acute migraine medication utilization in patients prescribed migraine prophylaxis. METHODS: For this retrospective cohort study, the Health Core Integrated Research Database provided pharmacy/medical claims data from 5 commercial health insurance plans (ie, excluding Medicare and Medicaid) on adult patients with migraine. Eligible patients had >or=1 pharmacy claim for a migraine prophylactic medication between July 1, 2000, and May 31, 2005, and >or=12 U of any combination of acute treatment (serotonin receptor agonist [triptan], ergotamine, or ergotamine combination) dispensed during the 180-day period preceding a first pharmacy claim for a prophylactic medication (index date). The prophylactic medication identified at index date was used for categorizing patients into 1 of 4 cohorts: amitriptyline, propranolol/timolol, divalproex sodium, or topiramate (reference). Kaplan-Meier curves were used for evaluating unadjusted risk for discontinuation over time, and a multivariate Cox proportional hazards model was developed to analyze factors associated with discontinuation of prophylactic medication. RESULTS: A total of 12,783 patients met the inclusion criteria and were included in the analysis (amitriptyline, 3749; propranolol/timolol, 2718; divalproex sodium, 1644; and topiramate, 4672). The mean (SD) ages were not significantly different across cohorts (43.9 [11.3], 42.0 [11.1], 43.1 [11.3], and 43.9 [10.6] years, respectively). The mean duration of treatment was significantly longer (131 [184] days) with topiramate compared with amitriptyline (94 [152] days), propranolol/ timolol (119 [180] days), and divalproex sodium (109 [158] days) (P < 0.001, P = 0.005, and P<0.001,respectively). The risks for discontinuing prophylactic treatment were 23%, 6%, and 11% higher with amitriptyline, propranolol/timolol, and divalproex sodium, respectively, compared with topiramate (P<0.001, P = 0.024, and P <0.001). Patients prescribed topiramate had a higher mean consumption rate of triptans preindex; postindex, decreases in triptan use were observed in all cohorts, although the magnitude of the decrease was greatest in patients prescribed topiramate compared with the other cohorts. CONCLUSIONS: In this study, prescription of topiramate was associated with greater persistence with prophylactic treatment than the other prophylactic drugs. Furthermore, greater reductions in acute treatment utilization, particularly triptans, were observed among patients prescribed topiramate compared with the other prophylactic cohorts.

Attainment of combined optimal lipid values and the impact of lipid medication on cardiovascular outcomes and costs in a commercially insured population in the US.

OBJECTIVE: To determine factors associated with the achievement of optimal lipid values (OLVs) and subsequent impact on clinical and economic outcomes. METHODS: An observational managed care database analysis was conducted among treatment-naïve adults with elevated cardiovascular (CV) risk, >or=12 months follow-up and full lipid panel from the 1st January 2002 to the 28th February 2005. Achievement of guideline-based levels for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides was evaluated via laboratory data. Annual CV-attributable resource utilisation was assessed via medical and pharmacy claims data. Clinical and economic outcomes associated with the achievement of OLVs were assessed using multivariate regression. RESULTS: A total of 52,778 patients were followed for a mean (standard deviation) of 27 (10) months with 13% achieving combined OLVs at baseline and 23% after 4 years. Of patients, 69% did not initiate lipid-modifying medication. The achievement of combined OLVs reduced the risk of CV event (odds ratio=0.86; 95% confidence interval 0.78-0.95), resource utilisation (inpatient visits: 3.36 vs. 4.41 per 100 patient years, p<0.0001; emergency department visits: 1.1 vs. 2.4 per 100 patient years, p<0.05) and costs: $703 vs. $903 per patient year, p<0.0001. CONCLUSIONS: Simultaneous achievement of OLVs was rare in this patient population. Physicians should be encouraged to manage multiple risk factors aggressively to improve clinical and economic outcomes associated with CV disease.

Treatment patterns among patients with psoriasis using a large national payer database in the United States: a retrospective study.

AIM: To characterize treatment patterns of psoriasis patients in a large US managed care database. MATERIALS AND METHODS: Adults with newly-diagnosed psoriasis were identified from July 3, 2006-August 31, 2014. Patients had continuous enrollment with medical and pharmacy benefits for ≥6 months prior to and ≥1 year following the index date. The index date was the point at which any of the following inclusion criteria were satisfied: first psoriasis diagnosis by a dermatologist, ≥ 2 psoriasis diagnoses ≥30 days apart, or a diagnosis of psoriasis followed by a claim for psoriasis therapy. Of primary interest was to measure and describe the following psoriasis treatment patterns: utilization rates, time to treatment discontinuation, and lines of therapy for various therapeutic classes of pharmacologic therapies. RESULTS: From the 128,308 patients identified, 53% were female, mean ± SD age was 50 ± 16 years, with median 3 years follow-up. Topicals were received by 86% of patients, non-biologic systemics by 13%, biologics by 6%, phototherapy by 5%, and 13% received no psoriasis-related medication. Median time from index to first treatment was 0 days for topical, 6 months for non-biologic systemic, and 6 months for biologic. Of those treated, first-line therapies included topical (95%), non-biologic systemic (4%), and biologic (2%). For those with second-line treatment, non-biologic systemic (71%) and biologic (30%) therapies were more common. The most common treatment pattern was topicals only (83%), while all other patterns comprised <5% of the treatment patterns observed. LIMITATIONS: Like other observational studies, limitations to consider when interpreting results include the 6-month pre-index period of no psoriasis or the psoriasis medication claim may not perfectly select only incident user of psoriasis medications, claims-based algorithms may not accurately represent true treatment patterns, absence of over-the-counter medications data, and having no trend analyses over time or between groups. CONCLUSIONS: While the majority of patients with psoriasis initiated a pharmacological therapy, a significant portion did not have a claim for any psoriasis medication. Topical treatments are the most commonly used treatments for psoriasis. Non-biologic systemic and biologic therapies were rarely used first line, but became more common in later lines of treatment.

Treatment Patterns of Newly Diagnosed Rheumatoid Arthritis Patients from a Commercially Insured Population.

INTRODUCTION: To describe treatment patterns in newly diagnosed rheumatoid arthritis (RA) patients in a large, nationally representative managed-care database. METHODS: Newly diagnosed RA patients were identified from 07/01/2006-08/31/2014. Patients had ≥ 1 RA diagnosis by a rheumatologist, or ≥ 2 non-rheumatologist RA diagnoses ≥ 30 days apart, or RA diagnosis followed by a disease-modifying antirheumatic drug (DMARD) prescription fill within 1 year. Patients were ≥ 18 years old at index (earliest date fulfilling diagnostic criteria) and had ≥ 6 and 12 months of pre- and post-index health plan enrollment, respectively. Patterns of DMARD treatment, including conventional synthetic DMARDs (csDMARD), tumor necrosis factor inhibitors (TNFi), non-TNFi, and Janus kinase inhibitors (JAKi), were captured during follow-up. RESULTS: Of the 63,101 RA patients identified, 73% were female; mean age was 57 years. During an average of 3.5 ± 2.1 years of follow-up, 45% of patients never received a DMARD, 52% received a csDMARD (94 ± 298 mean ± SD days from index), 16% a TNFi (315 ± 448 days), 4% a non-TNFi (757 ± 660 days), and < 1% a JAKi. Among DMARD recipients, the most common treatment patterns were: receiving csDMARDs only (68%), adding a TNFi as second-line therapy after initiation of a csDMARD (12%), and receiving only a TNFi (6%) during follow-up. Among those not on DMARDs, the all-cause usage of an opioid was 56% and 19% had chronic opioid use (≥ 180 days supplied). CONCLUSIONS: Despite American College of Rheumatology recommendations for DMARD treatment of RA, nearly half of newly diagnosed RA patients received no DMARD therapy during follow-up. These data identify a treatment gap in RA management. FUNDING: Eli Lilly & Company.

Clinical characteristics, patterns of lipid-lowering medication use, and health care resource utilization and costs among patients with atherosclerotic cardiovascular disease.

PURPOSE: The aim of this study was to investigate real-world patient characteristics, medication use, and health care resource utilization (HCRU) and costs among patients with clinical atherosclerotic cardiovascular disease (ASCVD) as defined by 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, to examine burden of disease and unmet needs, such as potential undertreatment. PATIENTS AND METHODS: This retrospective cohort study utilized a nationally representative managed care database to identify newly diagnosed ASCVD patients between January 1, 2007, and November 30, 2012 (index = first ASCVD diagnosis date) in the USA. Patients had ≥12-month pre-index (baseline) and ≥12-month post-index (follow-up) health plan enrollment and no baseline lipid-lowering medication (LLM). Patient characteristics, LLM utilization patterns, HCRU, and costs were examined for all patients and by subgroups based on LLM use pattern and/or follow-up low-density lipoprotein cholesterol (LDL-C) levels. RESULTS: A total of 128,017 ASCVD patients were identified with a mean (SD) age of 59 (13) years, 43.1% female, and 48.8% with ≥36-month follow-up. Within 12-month follow-up, 10.6% had high-intensity statins and 56.9% had no LLM fills. Baseline mean (SD) all-cause costs were $8,852 ($25,608). At 12-month follow-up, mean (SD) all-cause and ASCVD-related costs were $31,443 ($54,040) and $20,289 ($45,159), respectively. The 36-month analyses showed similar distributions. Multivariable analyses showed that age, gender, region, health insurance type, baseline comorbidities, baseline use of specific medications, baseline lipid profiles, and index ASCVD type were significantly associated with all-cause and ASCVD-related health care costs. CONCLUSION: Patients have nonoptimal treatment for ASCVD and substantial HCRU and costs associated with residual risk. Unmet needs and cost burdens of ASCVD patients merit additional investigation.

Cost Effectiveness of Achieving Targets of Low-Density Lipoprotein Particle Number Versus Low-Density Lipoprotein Cholesterol Level.

A recent analysis of a commercially insured US population found fewer cardiovascular disease (CVD) events in high-risk patients attaining low levels of low-density lipoprotein (LDL), as measured by LDL particle number (LDL-P) versus low LDL cholesterol (LDL-C). Here, we investigated the cost effectiveness of LDL-lowering therapy guided by LDL-P. Patients were selected from the HealthCore Integrated Research Database and followed for 12 to 36 months. Patients who achieved LDL-P <1,000 nmol/l were placed into the LDL-P cohort, whereas those without LDL-P tests, but who achieved LDL-C <100 mg/dl, were placed into the LDL-C cohort. CVD-related costs included all health plan paid amounts related to CVD events or lipid management. Cost effectiveness was assessed through incremental cost-effectiveness ratios, defined as difference in total costs across the cohorts divided by difference in CVD events, measured over follow-up. Each cohort included 2,094, 1,242, and 705 patients over 12-, 24-, and 36-month follow-up. Patients in the LDL-P cohort received more aggressive lipid-lowering therapy and had fewer CVD events during follow-up compared to patients in the LDL-C cohort. This led to greater pharmacy costs and lower medical costs over time. Incremental cost-effectiveness ratio estimates ranged from $23,131 per CVD event avoided at 12 months to $3,439 and -$4,555 at 24- and 36-month follow-up, suggesting a high likelihood that achieving LDL-P <1,000 nmol/l is cost effective. In conclusion, LDL-lowering therapy guided by LDL-P was demonstrated to be cost effective, with greater clinical and economic benefit seen over longer time horizons and with the increased use of generic statins.

Personalized Care and the Role of Insulin as a Vehicle to Optimizing Treatments in Diabetes Care.

BACKGROUND: In patients with type 2 diabetes (T2D) with poor glycemic control, there is an unmet need for treatment optimization involving the initiation and/or intensification of insulin therapy, which is often delayed because of clinical inertia. Educational initiatives that target patients and physicians might be one way to address this need. OBJECTIVE: To evaluate the effectiveness of educational materials mailed to physicians and their patients in affecting initiation of insulin therapy and other health care outcomes. METHODS: This study, named PIVOTs (Personalized care and the role of Insulin as a Vehicle to Optimizing Treatments), used integrated medical and pharmacy claims data from the U.S.-based HealthCore Integrated Research Database between January 1, 2006, and April 4, 2014, to identify patients who were potential candidates for insulin therapy. Eligible patients were aged 18-75 years, currently enrolled in a commercial or Medicare Advantage health plan, with T2D diagnosis codes. Patients selected for insulin treatment education had glycated hemoglobin A1c (A1c) > 10%, irrespective of the number of noninsulin antihyperglycemic drugs used, or A1c > 8.0% and ≤ 10% while receiving ≥ 2 noninsulin antihyperglycemic drugs. For each identified patient, a corresponding treating physician was identified on a hierarchical basis. Physician-level randomization was conducted to assign physicians and their linked patients to the following 4 cohorts: (1) a cross-sectional cohort in which educational materials were sent to patients and physicians on a single outreach date; (2) a longitudinal cohort in which educational materials were sent to patients and physicians on 2 occasions, 3 months apart; (3) an enhanced cohort in which patients and physicians received the same mailings as the longitudinal cohort, plus physicians were invited to attend a 1:1 video conference academic detailing session; and (4) a control cohort in which patients and physicians did not receive any educational materials. Insulin initiation rates, A1c levels, and medical and pharmacy costs were assessed from claims over 6 and 12 months follow-up within each cohort. RESULTS: Mean insulin initiation rates at 12 months ranged from 9.2%-10.3% (all patients) to 12.3%-14.9% (subset with baseline A1c ≥ 9.0%), with similar rates across the intervention and control cohorts. Reductions in A1c from baseline were also similar across cohorts for all patients (0.1%-0.6%), as well as for those with a baseline A1c ≥ 9.0% (0.9%-1.6%). Approximately 14%-20% of patients achieved A1c < 7.0%, with no differences across cohorts. Changes in mean total all-cause and diabetes-related health care costs were also similar across cohorts. CONCLUSIONS: The findings of this real-world, randomized intervention call into question the value of educational mailings as a means to overcoming clinical inertia and improving health outcomes in patients with T2D, at least in the context of insulin initiation. DISCLOSURES: This study was funded by Sanofi US. Bieszk and Wei are employees of Sanofi US. Grabner, Barron, and Quimbo are employees of HealthCore, which was under contract with Sanofi US for the conduct of this study. Yan is an employee of PHAR, LLC and was employed by HealthCore at the time this study was conducted and completed. Biel is an employee of Anthem. Chu is a consultant for Sanofi US; a member of the lecture bureaus for AstraZeneca, Eli Lilly, and Sanofi US; and has received research funding from Novo Nordisk. Study concept and design were contributed by Bieszk, Grabner, Wei, Quimbo, and Barron. Yan, Barron, Quimbo, and Grabner collected the data, which were interpreted by Biel, Chu, Bieszk, and Wei, with assistance from the other authors. The manuscript was written by Bieszk, with assistance from the other authors, and revised by Bieszk, Grabner, Biel, and Chu, along with the other authors. Part of this work was presented in poster format at the 76th Scientific Sessions of the American Diabetes Association; June 10-14, 2016; New Orleans, Louisiana.

A validation of clinical data captured from a novel Cancer Care Quality Program directly integrated with administrative claims data.

BACKGROUND: Data from a Cancer Care Quality Program are directly integrated with administrative claims data to provide a level of clinical detail not available in claims-based studies, and referred to as the HealthCore Integrated Research Environment (HIRE)-Oncology data. This study evaluated the validity of the HIRE-Oncology data compared with medical records of breast, lung, and colorectal cancer patients. METHODS: Data elements included cancer type, stage, histology (lung only), and biomarkers. A sample of 300 breast, 200 lung, and 200 colorectal cancer patients within the HIRE-Oncology data were identified for medical record review. Statistical measures of validity (agreement, positive predictive value [PPV], negative predictive value [NPV], sensitivity, specificity) were used to compare clinical information between data sources, with medical record data considered the gold standard. RESULTS: All 300 breast cancer records reviewed were confirmed breast cancer, while 197 lung and 197 colorectal records were confirmed (PPV =0.99 for each). The agreement of disease stage was 85% for breast, 90% for lung, and 94% for colorectal cancer. The agreement of lung cancer histology (small cell vs non-small cell) was 97%. Agreement of progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2 status biomarkers in breast cancer was 92%, 97%, and 92%, respectively; epidermal growth factor receptor and anaplastic lymphoma kinase agreement in lung was 97% and 92%, respectively; and agreement of KRAS status in colorectal cancer was 95%. Measures of PPV, NPV, sensitivity, and specificity showed similarly strong evidence of validity. CONCLUSION: Good agreement between the HIRE-Oncology data and medical records supports the validity of these data for research.

Comparison of costs associated with the use of etanercept, infliximab, and adalimumab for the treatment of rheumatoid arthritis.

A retrospective study of health plan costs related to rheumatoid arthritis (RA) revealed that etanercept was associated with the lowest drug and outpatient costs to the health plan than infliximab and adalimumab. Compared with etanercept, infliximab was related to 55% higher postindex RA-related monthly total health care costs paid by the health plan, based on adjusted analyses (95% confidence interval, 1.47-1.64). Patients receiving adalimumab had 12% higher costs (95% confidence interval, 1.04-1.21). The study showed the average dispensing dose increase was greatest for infliximab (17.4%) and least for etanercept (4.1%).

The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting.

PURPOSE: To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics. MATERIALS AND METHODS: This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. RESULTS: We identified 1,832 palonosetron and 2,387 other 5-HT3 RA ("other") patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019). CONCLUSION: Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs.

Cardiovascular risk in patients achieving low-density lipoprotein cholesterol and particle targets.

OBJECTIVES: Previous research suggests that LDL particle number (LDL-P) may be a better tool than LDL cholesterol (LDL-C) to guide LDL-lowering therapy. Using real-world data, this study has two objectives: [1] to determine the incidence of CHD across LDL-P thresholds; and [2] to compare CHD/stroke events among patients achieving comparably low LDL-P or LDL-C levels. METHODS: A claims analysis was conducted among high-risk patients identified from the HealthCore Integrated Research Database(SM). The impact of LDL levels on risk was compared across cohorts who achieved LDL-P <1000 nmol/L or LDL-C <100 mg/dL. Cohorts were matched to balance demographic and comorbidity differences. RESULTS: Among 15,569 patients with LDL-P measurements, the risk of a CHD event increased by 4% for each 100 nmol/L increase in LDL-P level (HR 1.04; 95% CI 1.02-1.05, p < .0001). The comparative analysis included 2,094 matched patients with ≥12 months of follow-up, 1,242 with ≥24 months and 705 with ≥36 months. At all time periods, patients undergoing LDL-P measurement were more likely to receive intensive lipid-lowering therapy and had a lower risk of CHD/stroke than those in the LDL-C cohort (HR: 0.76; 95% CI: 0.61-0.96; at 12 months). CONCLUSIONS: In this real-world sample of commercially insured patients, higher LDL-P levels were associated with increased CHD risk. Moreover, high-risk patients who achieved LDL-P <1000 nmol/L received more aggressive lipid-lowering therapy than patients achieving LDL-C <100 mg/dL, and these differences in lipids and therapeutic management were associated with a reduction in CHD/stroke events over 12, 24 and 36 months follow-up.

Clinical and economic outcomes among patients with diabetes mellitus initiating insulin glargine pen versus vial.

BACKGROUND: Insulin pens may help patients reach glycated hemoglobin (HbA1c) target levels, but a substantial proportion of patients continue to use insulin vials/syringes. The objective of the current study was to evaluate real-world clinical and economic outcomes of patients with type 2 diabetes mellitus (T2DM) initiating insulin glargine via pen delivery (pen) or vial/syringe (vial) within a large managed-care population in the United States. METHODS: This retrospective administrative claims study used data on adult, insulin-naïve patients with T2DM treated with ≥ 1 oral antidiabetic or glucagon-like peptide-1 receptor agonist at baseline. The index date was the earliest pen or vial prescription date. Propensity score matching (1:1) of patients in the pen and vial cohorts was used when comparing 1-year outcomes, including treatment persistence and adherence, HbA1c levels, hypoglycemia rates, and all-cause and diabetes-related health care costs (computed as paid amounts on claims). RESULTS: Patients in the matched cohorts (n = 733 per cohort) were well balanced with regard to demographics (mean age 52 years; 43% women), clinical measures (mean HbA1c level, 9.4%; mean Quan-Modified Charlson Comorbidity Index score, 0.9), and health care utilization at baseline. Following initiation of insulin glargine, pen patients were more persistent (60.6% vs 50.1%; P < 0.001) and adherent (medication possession ratio, 0.73 vs 0.57; P < 0.001), with lower HbA1c levels during follow-up (mean adjusted change, -1.05 vs -0.73; P < 0.001), compared with vial patients. Hypoglycemic events occurred at similar rates across pen and vial cohorts (3.8% vs 5.2%, respectively; P = 0.21). Study drug costs were higher among pen users ($1164 vs $762, respectively; P < 0.001), but this did not translate into higher total all-cause or diabetes-related costs. CONCLUSION: For patients with diabetes newly initiating insulin glargine, using an insulin pen device was associated with increased therapy persistence and adherence, and lower HbA1c levels relative to vial/syringe, without increasing total all-cause or diabetes-related costs.

Using observational data to inform the design of a prospective effectiveness study for a novel insulin delivery device.

OBJECTIVE: To inform the design and assess the feasibility of a prospective effectiveness study evaluating an insulin delivery device for patients with diabetes mellitus to be conducted within the membership of a large US commercial insurer. METHODS: Providers who issued ≥1 insulin prescription between January 1, 2011 and September 30, 2011 were selected from administrative claims contained in the HealthCore Integrated Research Database(SM). Adult diabetes patients with visits to these providers were identified. Providers were dichotomized into high- (HVPs) and low-volume providers (LVPs) based on median number of diabetes patients per provider. RESULTS: We identified 15,349 HVPs and 15,313 LVPs (median number of patients = 14). Most HVPs were located in the Midwest (6,291 [41.0%]) and South (5,092 [33.2%]), while LVPs were evenly distributed across regions. Over 80% (12,769) of HVPs practiced family or internal medicine; 6.4% (989) were endocrinologists. HVPs prescribed insulin to an average of 25% of patients. Patients of HVPs (522,527) had similar characteristics as patients of LVPs (80,669), except for geographical dispersion, which followed that of providers. Approximately 65% of patients were aged 21-64 years and 97% had type 2 diabetes. Among patients with ≥1 available HbA1C result during 2011 (103,992), 48.3% (50,193) had an average HbA1C ≥7.0%. Among patients initiating insulin, 79.6% (22,205) had an average HbA1C ≥7.0%. CONCLUSION: The observed provider and patient populations support the feasibility of the prospective study. Sampling of patients from HVPs is efficient while minimizing bias as patient characteristics are similar to those from LVPs. The study also highlights unmet needs for improved glycemic control since approximately half of patients with diabetes are not on goal.

The INITIATOR study: pilot data on real-world clinical and economic outcomes in US patients with type 2 diabetes initiating injectable therapy.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) progression often results in treatment intensification with injectable therapy to maintain glycemic control. Using pilot data from the Initiation of New Injectable Treatment Introduced after Anti-diabetic Therapy with Oral-only Regimens study, real-world treatment patterns among T2DM patients initiating injectable therapy with insulin glargine or liraglutide were assessed. METHODS: This was a retrospective analysis of claims from the OptumInsight™ (OI; January 1, 2010 to July 30, 2010) and HealthCore(®) (HC; January 1, 2010 to June 1, 2010) health insurance databases. Baseline characteristics, health care resource utilization, and costs were compared between adults with T2DM initiating injectable therapy with insulin glargine pen versus liraglutide. Follow-up outcomes, including glycated hemoglobin A1c (A1C), hypoglycemia, health care utilization, and costs, were assessed. RESULTS: At baseline, almost one in three liraglutide patients (OI, n = 363; HC, n = 521) had A1C <7.0%, while insulin glargine patients (OI, n = 498; HC, n = 1,188) had poorer health status, higher A1C (insulin glargine: 9.8% and 9.1% versus liraglutide: 7.9% and 7.7%, OI and HC, respectively, both P < 0.001), and were less likely to be obese (insulin glargine: 10.8% and 9.2% versus liraglutide: 17.4% and 18.8%, OI and HC, respectively, both P < 0.01). The percentage of patients experiencing a hypoglycemic event was numerically higher for insulin pen use for both cohorts (OI 4.4% versus 3.0%; HC 6.2% versus 2.3%). During follow-up, in the insulin glargine cohort, annualized diabetes-related costs remained unchanged ($8,344 versus $7,749 OI, and $7,094 versus $7,731 HC), despite a significant increase in pharmacy costs, due to non-significant decreases in medical costs, while the liraglutide cohort had a significant increase in annualized diabetes-related costs ($4,510 versus $7,731 OI, and $4,136 versus $7,111 HC; both P < 0.001) due to a non-significant increase in medical costs coupled with a significant increase in pharmacy costs. CONCLUSION: These descriptive data identified differences in demographic and baseline clinical characteristics among patients initiating injectable therapies. The different health care utilization and cost patterns warrant further cost-effectiveness analysis.

Hypoglycemia in patients with type 2 diabetes using concomitant exenatide BID and long-acting insulin therapy.

OBJECTIVE: The objective of this study was to examine the frequency of hypoglycemia among patients with type 2 diabetes who had concomitantly used exenatide BID (exenatide) and long-acting insulin and continued this combination vs those who continued long-acting insulin alone. METHODS: Retrospective analyses, using a large managed care database, were used to estimate the frequency of hypoglycemia (episodes/patient/6 months) for patients who concomitantly used exenatide and long-acting insulin during a 6-month follow-up period. RESULTS: From among 2082 patients on concomitant exenatide and long-acting insulin, those who continued this combination (n=472) had a lower frequency of hypoglycemia compared to those who remained on long-acting insulin alone (n=312) (0.03 ± 1.9 vs 0.10 ± 1.01 [episodes/patient/6 months]; p<0.0001). LIMITATIONS: Only hypoglycemia that required medical intervention (coded for hypoglycemia) was captured. The study could not evaluate any association between insulin dose titration and hypoglycemia or examine other outcomes such as HbA1c, weight, and body mass index, due to lack of data availability. CONCLUSIONS: Patients who concomitantly used exenatide BID and long-acting insulin experienced a lower rate of hypoglycemia.

Subacute lack of asthma control as a predictor of subsequent acute asthma exacerbation in a managed care population.

OBJECTIVE: To evaluate whether an assessment of subacute lack of asthma control (SALAC) predicts subsequent acute asthma exacerbation (AAE). STUDY DESIGN: This retrospective administrative claims study used medical and pharmacy claims from the HealthCore Integrated Research Database to identify patients aged 6 to 64 years with asthma and having 3 years' continuous enrollment from January 1, 2003, through December 31, 2005. METHODS: Study inclusion criteria were at least 2 outpatient visits or at least 1 hospitalization or emergency department (ED) visit with an asthma diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 493.xx) in at least 1 of 3 years (2003-2005). SALAC was defined as more than 4 asthma outpatient visits or more than 5 short-acting beta2-agonist (SABA) prescriptions per year, and AAE was defined as at least 1 hospitalization or ED visit with a primary asthma diagnosis or an oral corticosteroid burst prescription. Generalized estimating equations modeled the risk of subsequent-year AAE as a function of 2 sets of variables to determine the independent effect of prior-year SALAC and its components on subsequent-year AAE. The first set included age, sex, geographic region, prior year AAE, and prior-year SALAC. The second set included age, sex, geographic region, prior-year AAE, high prior-year SABA use, and frequent prior-year asthma outpatient visits. RESULTS: Of 35,806 patients with asthma, 46.6% were male, and 35.8% were younger than 18 years. The mean annual prevalence of SALAC was 12.1%. Controlling for all other variables, the generalized estimating equation results indicate that prior-year SALAC is associated with a 60% increased risk of subsequent-year AAE (P <.001). Increased prior-year asthma outpatient visits and SABA use are associated with 34% and 85%, respectively, greater risks of subsequent-year AAE (P <.001 for both). CONCLUSION: SALAC and its components can aid in predicting patients at risk for AAE.