David M. Kern

Impact of natalizumab on patient-reported outcomes in multiple sclerosis: a longitudinal study

BackgroundNatalizumab (Tysabri, Biogen Idec and Elan Pharmaceuticals) significantly reduces the relapse rate and disability progression, and improves health-related quality of life (HRQoL), in patients with relapsing-remitting multiple sclerosis. We investigated the impact of natalizumab on patient-reported outcomes (PROs) in a real-world setting.MethodsPRO data were collected from patients enrolled in a longitudinal real-world study using validated measures administered as surveys before the patients initiated natalizumab treatment and after the 3rd, 6th, and 12th monthly infusion. HRQoL, ability to carry out daily activities, disability level, and impact on cognitive functioning and fatigue were assessed.ResultsA total of 333 patients completed 12 months of assessments. After 12 months of natalizumab treatment, 69% to 88% of patients reported a positive outcome (either an improvement or no further decline) in all PRO measures assessed. Significant improvements in general and disease-specific HRQoL were observed after three infusions, both with physical (p < .01) and psychological (p < .001) measures, and were sustained after 12 infusions (all p < .001). The impact of multiple sclerosis on cognitive functioning and fatigue was significantly reduced (both p < .001 after 3 and 12 infusions).ConclusionsPRO measures were improved with natalizumab in a real-world setting. The improvements were observed as early as after 3 months and sustained over a 12-month period. The improvements in PROs show that, in clinical practice, the clinical benefits of natalizumab are translated into patient-reported benefits.

Understanding CKD among patients with T2DM: prevalence, temporal trends, and treatment patterns—NHANES 2007–2012

Objective To describe the estimated prevalence and temporal trends of chronic kidney disease (CKD) treatment patterns, and the association between CKD and potential factors for type 2 diabetes mellitus (T2DM) in different demographic subgroups. Research design and methods This was a cross-sectional analysis of adults with T2DM based on multiple US National Health and Nutrition Examination Survey (NHANES) datasets developed during 2007–2012. CKD severity was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines using the CKD Epidemiology Collaboration (CKD-EPI) equation: mild to moderate=stages 1–3a; moderate to kidney failure=stages 3b–5. Multivariable logistic regression analyses were performed to assess the associations between CKD and potential factors. Results Of the adult individuals with T2DM (n=2006), age-adjusted CKD prevalence was 38.3% during 2007–2012; 77.5% were mild-to-moderate CKD. The overall age-adjusted prevalence of CKD was 40.2% in 2007–2008, 36.9% in 2009–2010, and 37.6% in 2011–2012. The prevalence of CKD in T2DM was 58.7% in patients aged ≥65 years, 25.7% in patients aged <65 years, 43.5% in African-Americans and Mexican-Americans, and 38.7% in non-Hispanic whites. The use of antidiabetes and antihypertensive medications generally followed treatment guideline recommendations. Older age, higher hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and having hypertension were significantly associated with CKD presence but not increasing severity of CKD. Conclusions CKD continued to be prevalent in the T2DM population; prevalence remained fairly consistent over time, suggesting that current efforts to prevent CKD could be improved overall, especially by monitoring certain populations more closely.

Treatment pattern changes in high-risk patients newly initiated on statin monotherapy in a managed care setting.

BACKGROUND For high-risk patients who do not achieve guideline-recommended LDL-C levels, more intensive treatment including statin-uptitration to higher doses or potency, as well as combination therapy may be considered. A better understanding of statin treatment patterns in real-world clinical practice may contribute to improved lipid-lowering management in these patients. OBJECTIVE We determined treatment pattern changes among patients with high risk of cardiovascular disease who were not at low-density lipoprotein cholesterol (LDL-C) goal on statin monotherapy. METHODS Treatment pattern changes were evaluated among patients newly initiated on statins between January 1, 2006, and August 31, 2009, in the HealthCore Integrated Research Database. Rates and mean time to first and second treatment changes were examined in patients with claims for coronary heart disease (CHD), atherosclerotic vascular disease (AVD), and diabetes mellitus during 12 months before index, who were not at LDL-C <70 mg/dL at their first-eligible LDL-C test (≥ 4 weeks after index). Therapy change was assessed for 12 months after the LDL-C result. RESULTS Of 11,473 eligible subjects, 61.3% had diabetes, 26.6% had CHD and AVD, and 12.1% had CHD and AVD and diabetes. At index, patients were prescribed medium-potency levels of statins, including simvastatin (44.7%), atorvastatin (31.5%), and other statins (23.8%). Mean ± SD LDL-C before statin initiation was 138 ± 34 mg/dL, and at the first-eligible LDL-C result after index, it was 101 ± 25 mg/dL. During follow-up, 7444 subjects (64.9%) experienced a first treatment change, with mean time to change of 93.8 ± 92 days, whereas 4029 (36.1%) had no treatment change. Discontinuation of index therapy occurred in 46.9% of subjects and medication switches or titration in 18.0% (index statin titration, switch to other statins, other lipid-lowering therapies [LLT], including ezetimibe). Of the discontinuers, 27.4% restarted LLT. Of subjects with a first treatment change who did not discontinue, 48.9% experienced a second therapy change. Results were similar between the 3 high-risk groups. CONCLUSIONS In this managed-care setting, among patients with high risk of cardiovascular disease who were not at LDL-C goal, statins were usually started at medium-potency doses without being titrated up, whereas nearly one-half had a discontinuation of LLT within 12 months. These treatment patterns indicate the need for better patient and provider education as well as other system-wide modifications to improve medication adherence.

Asthma and Chronic Obstructive Pulmonary Disease Overlap Syndrome: Doubled Costs Compared with Patients with Asthma Alone☆

BACKGROUND Patients with asthma and chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) have more rapid disease progression and more exacerbations than do those with either condition alone. Little research has been performed, however, in these patients. OBJECTIVE The objective was to summarize the health care utilization, costs, and comorbidities of patients with uncontrolled asthma and patients with ACOS. METHODS This retrospective analysis used medical and pharmacy claims from large commercial health plans. The study included patients 6 years or older with a diagnosis of asthma and one or more asthma exacerbation (index event). Patients were classified as having asthma alone or ACOS, and the two groups were matched for age, sex, region, index year, index month, and health plan type. Outcomes included rates of comorbid disease, health care utilization, and costs during the 12 months before and after the index exacerbation. RESULTS Among the matched patients with asthma (6,505 ACOS; 26,060 without COPD), mean annual all-cause health care costs were twice as high as for patients with ACOS (

Statin treatment patterns and clinical profile of patients with risk factors for coronary heart disease defined by National Cholesterol Education Program Adult Treatment Panel III

22,393 vs.

Validation of an administrative claims-based diagnostic code for pneumonia in a US-based commercially insured COPD population.

11,716; P < 0.0001). Asthma-related costs, representing 29% of total costs, were nearly twice as high among patients with ACOS (

Seasonal influenza vaccination trends from 2007-2011 in privately insured children and adults in the United States

6,319 vs. 3,356; P < 0.0001). Cost differences were driven by large differences in the proportions of patients with an inpatient hospitalization (34.0% vs. 14.6%; P < 0.0001) or emergency department visit (29.6% vs. 19.9%; P < 0.0001). Nearly all prespecified comorbid conditions were more prevalent in the ACOS group. CONCLUSIONS Patients with asthma and COPD had nearly double the health care costs as did patients with asthma without COPD. The overall disease profile of patients with asthma should be considered when managing patients, rather than treating asthma as a solitary condition.

Long-term cardiovascular risk and costs for myocardial infarction survivors in a US commercially insured population

Abstract Objective: To compare clinical characteristics, statin treatment patterns and adherence among patients at different risk for coronary heart disease (CHD) as defined by National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines. Methods: Patients ≥18 years old with ≥1 claim for dyslipidemia, ≥1 statin claim, or ≥1 LDL-C value ≥100 mg/dL were identified from 1 January 2007 to 31 July 2012. Patients were classified as low risk (LR) (0–1 risk factor: hypertension, age ≥45 years [men] or ≥55 years [women], or low HDL-C), moderate/moderately high risk (MR) (≥2 risk factors), high risk (HR) (CHD or CHD risk equivalent), or very high risk (VHR) (acute coronary syndrome, or established cardiovascular disease plus diabetes or metabolic syndrome). Medication use and lipid levels during the 12 months before and statin use during the 6 months after index were compared across risk groups. Results: There were 1,524,351 LR, 242,357 MR, 188,222 HR, and 57,469 VHR patients identified. Statin use was observed in 15% of all patients, but was higher in the VHR group (45%) versus LR (12%), MR (18%), and HR (29%) groups. Simvastatin accounted for 50%–52% of all statin use, and average statin dose was higher among VHR patients compared with all other groups. Adherence was low overall (mean proportion of days covered [PDC]: 0.57), but higher among VHR (0.69) versus others (mean PDC: 0.55, 0.59, and 0.59 in LR, MR, and HR groups, respectively). Conclusions: Statin treatment was low across all risk groups, and VHR patients had higher doses and better adherence compared with other risk groups. However, adherence was not optimal, indicating a potential limited benefit from statin treatment.

Initiation Patterns of Statins in the 2 Years After Release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Management Guideline in a Large US Health Plan

Objective To estimate the accuracy of claims-based pneumonia diagnoses in COPD patients using clinical information in medical records as the reference standard. Methods Selecting from a repository containing members’ data from 14 regional United States health plans, this validation study identified pneumonia diagnoses within a group of patients initiating treatment for COPD between March 1, 2009 and March 31, 2012. Patients with ≥1 claim for pneumonia (International Classification of Diseases Version 9-CM code 480.xx–486.xx) were identified during the 12 months following treatment initiation. A subset of 800 patients was randomly selected to abstract medical record data (paper based and electronic) for a target sample of 400 patients, to estimate validity within 5% margin of error. Positive predictive value (PPV) was calculated for the claims diagnosis of pneumonia relative to the reference standard, defined as a documented diagnosis in the medical record. Results A total of 388 records were reviewed; 311 included a documented pneumonia diagnosis, indicating 80.2% (95% confidence interval [CI]: 75.8% to 84.0%) of claims-identified pneumonia diagnoses were validated by the medical charts. Claims-based diagnoses in inpatient or emergency departments (n=185) had greater PPV versus outpatient settings (n=203), 87.6% (95% CI: 81.9%–92.0%) versus 73.4% (95% CI: 66.8%–79.3%), respectively. Claims-diagnoses verified with paper-based charts had similar PPV as the overall study sample, 80.2% (95% CI: 71.1%–87.5%), and higher PPV than those linked to electronic medical records, 73.3% (95% CI: 65.5%–80.2%). Combined paper-based and electronic records had a higher PPV, 87.6% (95% CI: 80.9%–92.6%). Conclusion Administrative claims data indicating a diagnosis of pneumonia in COPD patients are supported by medical records. The accuracy of a medical record diagnosis of pneumonia remains unknown. With increased use of claims data in medical research, COPD researchers can study pneumonia with confidence that claims data are a valid tool when studying the safety of COPD therapies that could potentially lead to increased pneumonia susceptibility or severity.

Comparative Effectiveness of Budesonide-Formoterol Combination and Fluticasone-Salmeterol Combination for Asthma Management: A United States Retrospective Database Analysis

BACKGROUND To ensure adequate protection from seasonal influenza in the US, the Advisory Committee on Immunization Practices recommends vaccination of all persons aged 6 months or older, with rare exceptions. It also advises starting vaccination as soon as available and continuing throughout the influenza season. This study examined US seasonal vaccination trends during five consecutive influenza seasons in privately-insured children and adults. METHODS This retrospective, observational cohort study examined trends in influenza vaccination during the 2007-2008 through 2011-2012 influenza seasons using administrative claims data from a large national insurer. RESULTS The size of analysis population ranged from 1144,098 to 1245,487 (children, ≥6 months-17 years of age) and from 3931,622 to 4158,223 (adults, 18-64 years of age). Vaccination frequency increased through 2010-2011, was most frequent in young children, and decreased with age. Vaccination rates were highest in the Northeast and lowest in the West and were higher in individuals with frequent outpatient office visits than in those with no or rare visits, with larger differences seen in children. Between 2007 and 2011, the use of preservative-free inactivated vaccine increased, the use of multidose vaccines containing preservatives decreased, and the use of live attenuated influenza vaccines increased among children 2-17 years of age. From 2007-2008 through 2009-2010, the timing of vaccination each year began earlier than the previous one; it remained stable from 2009-2010 through 2011-2012. CONCLUSION Annual influenza vaccination claims for privately-insured children and adults increased and shifted earlier from 2007 through 2009-2011. During the 2011-2012 influenza season, 25.4% of children aged 6 months-17 years and 12.3% of adults aged 18-64 years were vaccinated. Increasing influenza vaccination should remain a priority, and alternative venues for seasonal influenza vaccination should be considered in order to meet the Healthy People 2020 goal of 80% to 90% coverage among children.