Cost-utility analyses of targeted immunomodulators in rheumatoid arthritis: systematic review.

Aims: Cost-utility (CU) modeling is a common technique used to determine whether new treatments represent good value for money. As with any modeling exercise, findings are a direct result of methodology choices, which may vary widely. Several targeted immuno-modulators have been launched in recent years to treat moderate-to-severe rheumatoid arthritis (RA) which have been evaluated using CU methods. Our objectives were to identify common and innovative modeling choices in moderate-to-severe RA and to highlight their implications for future models in RA.Materials and methods: A systematic literature search was conducted to identify CU models in moderate-to-severe RA published from January 2013 to June 2019. Studies must have included an active comparator and used quality-adjusted life-years (QALYs) as the common measure of effectiveness. Modeling methods were characterized by stakeholder perspective, simulation type, mapping between parameters, and data sources.Results: Thirty-one published modeling studies were reviewed spanning 13 countries and 9 drugs, with common methodological choices and innovations observed among them. Over the evaluated time period, we observed common methods and assumptions that are becoming more prominent in the RA CU modeling landscape, including patient-level simulations, two-stage models combining trial results and real-world evidence, real-world treatment durations, long-term health consequences, and Health Assessment Questionnaire (HAQ)-related hospitalization costs. Models that consider the societal perspective are increasingly being developed as well.Limitations: This review did not consider studies that did not report QALYs as a utility measure, models published only as conference abstracts, or cost-consequence models that did not report an incremental CU ratio.Conclusions: CU modeling for RA increasingly reflects real-world conditions and patient experiences which are anticipated to provide better information in the assessment of health technologies. Future CU models in RA should consider applying the observed advances in modeling choices to optimize their CU predictions and simulation of real-world outcomes.

Do Research Groups Align on an Intervention's Value? Concordance of Cost-Effectiveness Findings Between the Institute for Clinical and Economic Review and Other Health System Stakeholders.

The Institute for Clinical and Economic Review (ICER) employs fixed cost-effectiveness (CE) thresholds that guide their appraisal of an intervention's long-term economic value. Given ICER's rising influence in the healthcare field, we undertook an assessment of the concordance of ICER's CE findings to the published CE findings from other research groups (i.e., "non-ICER" researchers including life science manufacturers, academics, and government institutions). Disease areas and pharmaceutical interventions for comparison were determined based on ICER evaluations conducted from 1 January 2015 to 31 December 2017. A targeted literature search was conducted for non-ICER CE publications using PubMed. Studies had to be conducted from the US setting, include the same disease characteristics (e.g., disease severity; treatment history), incorporate the same pharmaceutical interventions and comparison groups, and present incremental costs per quality-adjusted life-year (QALY) gained from the healthcare sector or payer perspective. Discordance was measured as the proportion of unique interventions that would have had more favorable valuations (i.e., low, intermediate, high value-for-money) if the CE findings from other research groups had been used for decision making instead of ICER's findings. More favorable valuations were defined as transitioning from low value (as determined by ICER) to intermediate or high value (as determined by other researchers) and from intermediate value (as determined by ICER) to high value (as determined by other researchers). Among the 13 non-ICER studies meeting inclusion criteria, six disease areas and 14 interventions were assessed. Of the 14 interventions, a more favorable valuation would have been recommended for ten therapies if the CE ratios from other research groups had been used for decision making instead of ICER's findings, representing a 71.4% (10/14) discordance rate. Moreover, these discrepancies were found in each of the evaluated disease areas, with the largest number of discordant valuations found in rheumatoid arthritis (five out of six interventions were discordant) followed by one valuation each in multiple sclerosis (one out of three), non-small cell lung cancer (one out of two), multiple myeloma (one out of one), high cholesterol (one out of one), and congestive heart failure (one out of one). Our findings indicate high discordance when comparing ICER's appraisals to the CE findings of non-ICER researchers. To understand the value of new interventions, the totality of evidence on the CE of an intervention-including results from ICER and non-ICER modeling efforts-should be considered when making coverage and reimbursement decisions.

Costs and complications associated with transvenous lead reoperation in cardiac implantable electronic devices.

BACKGROUND: Cardiac implantable electronic device transvenous (TV) lead reoperations are projected to increase, and robust economic data are needed to assess the resulting financial impact and the cost-effectiveness of prevention and treatment strategies. This study estimates Medicare costs, and describes patterns of complications, in patients who underwent TV lead reoperation. METHODS AND RESULTS: Medicare data (2010-2014) were used to identify patients who underwent TV lead reoperation. Cumulative costs to Medicare, and rates of infection and mechanical complications were calculated from 180 days before, to 180 days after, lead reoperation. Multivariate analysis was used to estimate adjusted costs, and to examine the impact of complications on medical resource use and costs. There were 1691 patients, 63.2% of whom underwent inpatient lead reoperation. Overall, the mean age was 78.2 years, 39.6% were female, and 92.3% were white. The mean cumulative cost was $36 199 (95% confidence interval [CI], $31 864-$40 535) for TV lead repositioning, $27 701 (95% CI, $19 869-$35 534) for repair, and $54 442 (95% CI, $51 651-$57 233) for removal. Underlying infection was associated with increased odds of inpatient reoperation and of lead removal, as well as longer length of stay and higher costs. CONCLUSIONS: The economic consequences of TV lead reoperation are substantial. Strategies aimed at reducing reoperation, particularly lead removal, are likely to result in considerable cost offsets.

Validation of obesity coding among newly treated nonvalvular atrial fibrillation patients using an integrated electronic medical record and claims database.

Objective: To evaluate the validity of diagnosis codes for identifying obesity and morbid obesity among newly treated nonvalvular atrial fibrillation (NVAF) patients.Methods: An integrated electronic medical record (EMR) and claims database (1 January 2013-31 March 2018) was used. Adult patients with ≥1 claim for an oral anticoagulant (OAC) from 1 January 2014-30 September 2017 were identified (index date). Patients were required to have ≥1 atrial fibrillation diagnosis, no OAC use or valvular disease during the 12 months before index date, ≥12 months of continuous enrollment before and ≥6 months after index date, and ≥1 BMI measurement 6 months before or after index date. Patients with BMI ≥30 kg/m2 and BMI ≥40 kg/m2 were classified as obese and morbidly obese, respectively. Sensitivity, specificity and positive predictive value (PPV) were calculated to assess the validity of diagnosis codes for obesity and morbid obesity.Results: A total of 7501 patients met all selection criteria. Forty-six percent of patients had BMI ≥ 30 kg/m2, of whom about one-quarter had a BMI ≥ 40 kg/m2. Twenty-five percent and 10% of patients had a diagnosis code for obesity or morbid obesity, respectively. Sensitivity, specificity and PPV for obesity diagnosis codes were 48.67% (95% CI: 47.00%-50.35%), 95.24% (94.54%-95.88%) and 89.78% (88.32%-91.12%), respectively, and 62.75% (59.30%-66.11%), 96.46% (95.99%-96.89%) and 67.93% (64.43%-71.29%) for morbid obesity diagnosis codes, respectively.Conclusion: Among newly treated NVAF patients, obesity diagnosis codes had high PPV, high specificity and modest sensitivity. Morbid obesity diagnosis codes also had high specificity, but modest PPV and sensitivity. These findings have implications for case selection and control for obesity as a confounder in studies using a claims database.

Economic Burden of Treatment-Resistant Depression on the U.S. Health Care System.

BACKGROUND: Treatment-resistant depression (TRD), defined as episodes of depression that do not respond to ≥ 2 lines of adequate depression therapy, is associated with a high economic burden. Although the economic burden of TRD is reported elsewhere, its exact magnitude and current value is uncertain due to differences in methodology in TRD identification. OBJECTIVE: To compare all-cause health care resource utilization (HCRU) and associated health care payments among patients with TRD and those with depression but without TRD, using administrative claims data. METHODS: This retrospective cohort study used data from the Truven Health MarketScan Commercial and Medicare Supplemental Databases (October 1, 2008-September 30, 2016). All patients were aged ≥ 18 years, newly diagnosed with depression (≥ 1 inpatient admission or ≥ 2 outpatient visits with a primary or secondary depression diagnosis), and newly treated with depression therapy. The population included patients with and without TRD. Patients with TRD were defined as having been treated with ≥ 3 courses of depression therapy within a 360-day period (initiation of the third course served as the TRD index date), while patients without TRD (non-TRD) were defined as having been treated with 2 courses of depression therapy. TRD and non-TRD cohorts were matched using propensity scores. Using the TRD index date of their matched TRD pair, non-TRD patients were assigned a simulated index date following second-line therapy. Eligible TRD and non-TRD patients were continuously enrolled from a 12-month baseline period before the first course of therapy through a 12-month follow-up period beginning with the TRD index date and simulated index date, respectively. Annual all-cause HCRU and associated payments (2016 U.S. dollars) were assessed in aggregate and by place of service during the follow-up period and were compared between the matched cohorts using nonparametric Wilcoxon signed-rank tests. RESULTS: The matched analysis included 800 patients in each cohort. For both cohorts, the mean age of patients was 39 years, and 60% were female. All clinical characteristics and all-cause HCRU were comparable at baseline. Compared with non-TRD patients, TRD patients had a significantly higher mean number of all-cause emergency department (ED) visits (0.29 vs. 0.24), outpatient visits (18.0 vs. 13.4), and prescriptions (30.0 vs. 24.0; all P < 0.05) during the 12-month follow-up period. The TRD cohort also had significantly higher mean total all-cause health care payments ($9,890 vs. $6,848; P < 0.001) and mean payments by place of service (ED: $518 vs. $408; outpatient: $3,603 vs. $2,585; pharmacy: $2,613 vs. $1,837; all P < 0.05) compared with the non-TRD cohort. CONCLUSIONS: In relation to propensity score-matched non-TRD patients, TRD patients used significantly more resources (ED visits, outpatient visits, and number of prescriptions) and had significantly higher overall health care payments. These results serve to highlight the unmet need in patients with TRD, suggesting that improved and more effective management of these patients may help reduce the economic burden of disease. DISCLOSURES: This study was funded by Alkermes. Sussman and Menzin, employees of Boston Health Economics, were paid consultants, and Olfson, an employee of Columbia University Irving Medical Center, was an unpaid consultant to Alkermes in connection with the study and development of this research article. O'Sullivan and Shah are employees of the study sponsor. Results from this analysis were first presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting in Boston, MA, on April 23-26, 2018.

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.

Travel burden associated with rare cancers: The example of Merkel cell carcinoma.

BACKGROUND: There are limited data on the travel burden for cancer patients with rare tumor types, such as Merkel cell carcinoma (MCC). OBJECTIVE: The objective of this study was to understand the travel burden of MCC patients. METHODS: This study used data from an MCC registry at the Seattle Cancer Care Alliance (SCCA). All MCC patients enrolled at SCCA with a valid 3-digit ZIP code were included. Patients were followed up from January 1, 2012 until their last follow-up, death, or end of data (January 1, 2017). Travel burden was measured by one-way travel distance to SCCA from each patient's 3-digit ZIP code. Patient demographics, tumor characteristics, and follow-up visit were evaluated and stratified by one-way driving distance of ≤300 and >300 miles. RESULTS: A total of 391 MCC patients were included (68% men, mean age = 67 years [±SD = ±11 years], 67% residing in the West, and 70% white). At diagnosis, 53% of the patients had Stage III or IV MCC. Mean one-way distance traveled by patients was 1,137 (median: 813) miles, and 57% of patients traveled >300 miles. Compared to patients who traveled ≤300 miles, those who traveled >300 miles were more likely to be <70 years old (46% vs 65%; P < 0.001), were diagnosed with advanced stage (III or IV) MCC (46% vs 59%; P = 0.01), had shorter follow-up in the cancer registry (mean: 509 vs 212 days; P < 0.001), and had fewer visits during follow-up (mean: 5.2 vs 2.5; P < 0.001). CONCLUSIONS: In this single cancer center study, the majority of MCC patients trav-eled long distances to receive expert care. Longer travel distances appeared to be associated with younger age, a more advanced stage of cancer at study entry and fewer in-clinic visits, suggesting that travel burden may impact timely and adequate patient care for this rare cancer.

Cost-effectiveness analysis of erenumab for the preventive treatment of episodic and chronic migraine: Results from the US societal and payer perspectives.

Objectives To assess the cost-effectiveness of erenumab 140 mg ("erenumab") for the prophylactic treatment of episodic migraine and chronic migraine. Study design A hybrid Monte Carlo patient simulation and Markov cohort model was constructed to compare erenumab to no preventive treatment or onabotulinumtoxinA among adult ( ≥ 18 years) patients with episodic migraine and chronic migraine who failed prior preventive therapy from the US societal and payer perspectives. Methods Patients entered the model one at a time and were assigned to a post-treatment monthly migraine day category based on baseline monthly migraine days and treatment effect. Using monthly cycles, patients were followed for 2 years and accumulated costs and utilities associated with their post-treatment monthly migraine days. The primary outcome included the incremental cost-effectiveness ratio presented as cost per quality-adjusted life year gained. Results With an annual drug price of erenumab of $6900, treatment with erenumab in the societal perspective ranges from a dominant strategy versus no preventive treatment among chronic migraine patients to an incremental cost-effectiveness ratio of $122,167 versus no preventive treatment among episodic migraine patients. When excluding indirect costs (i.e. payer perspective), the incremental cost-effectiveness ratios are cost-effective among chronic migraine patients ($23,079 and $65,720 versus no preventive treatment and onabotulinumtoxinA, respectively), but not among episodic migraine patients ($180,012 versus no preventive treatment). Model results were sensitive to changes in monthly migraine days, health utilities, and treatment costs. Conclusion The use of erenumab may be a cost-effective approach to preventing monthly migraine days among patients with chronic migraine versus onabotulinumtoxinA and no preventive treatment in the societal and payer perspectives, but is less likely to offer good value for money for those with episodic migraine, unless lost productivity costs are considered.

Comorbidity in US patients with multiple sclerosis.

OBJECTIVE: To assess the trends in the prevalence of comorbidities in US patients with multiple sclerosis (MS), and the association of demographic characteristics with the presence of comorbidities. STUDY DESIGN: A retrospective analysis was conducted from a sample of 5 million patients from the IMS Health Real World Data Adjudicated Claims - US database. METHODS: Comorbidity in patients with MS was assessed by year (2006-2014), and logistic regression models evaluated the association of age, sex, and region with select comorbidities. RESULTS: The most common comorbidities from 2006 to 2014 were hyperlipidemia and hypertension (25.9%-29.7% of patients within an individual year), followed by gastrointestinal disease (18.4%-21.2% of patients) and thyroid disease (12.9%-17.1% of patients). The proportion with a claim for hyperlipidemia increased from 2006 to 2009, was stable from 2009 to 2011, and then declined from 2011 to 2014. The proportion with a claim for hypertension generally increased from 2006 to 2013, then declined from 2013 to 2014. The proportion with a claim for gastrointestinal disease, thyroid disease, and anxiety generally increased from 2006 to 2014. Claims for comorbidities were statistically significantly more likely among older age groups (p<0.05), with the exception of anxiety and alcohol abuse, which were statistically significantly less likely among older age groups. Claims for gastrointestinal disease (OR=0.75), thyroid disease (OR=0.36), chronic lung disease (OR=0.76), arthritis (OR=0.71), anxiety (OR=0.63), and depression (OR=0.69) were statistically significantly less likely among males versus females (all p<0.05). Claims for hyperlipidemia (OR=1.39), hypertension (OR=1.25), diabetes (OR=1.31), and alcohol abuse (OR=2.41) were significantly more likely among males (p<0.05). Many comorbidity claims were statistically significantly more likely in the Northeast and South compared with the Midwest and West. CONCLUSION: This study provides select comorbidity claims estimates in US patients with MS, and thus highlights the importance of comprehensive patient care approaches.

Factors associated with early initiation of disease-modifying drug treatment in newly-diagnosed patients with multiple sclerosis.

OBJECTIVE: To examine the time to first disease-modifying drug (DMD) treatment and to identify factors associated with early DMD initiation in newly-diagnosed patients with MS. METHODS: This retrospective cohort study included newly-diagnosed patients with MS from a US administrative claims database, aged 18-65 years, with a first MS diagnosis (ICD-9-CM code: 340.xx) between January 1, 2007 and June 30, 2013 (index date), continuous eligibility for 12 months pre- and 24 months post-index, and initiated DMD treatment within 2 years. Time to first DMD within 24 months post-index was evaluated. A logistic regression model predicted earlier initiation of DMD treatment (within 60 days of MS diagnosis). RESULTS: In total, 37.4% of patients initiated DMD treatment within 2 years of MS diagnosis and were included in the primary analysis (n = 7,124). Mean (standard deviation [SD]) time from MS diagnosis to first DMD was 112.6 (148.3) days (median = 51); 30.7% received first DMD in <30 days, 55.1% in <60 days, and 18.5% not until ≥180 days after diagnosis. Logistic regression found that younger age; not living in the Northeast; diagnoses of balance disorders, numbness, and optical neuritis; the absence of musculoskeletal diagnoses; and a neurologist visit or MRI within 90 days before diagnosis were associated with DMD initiation within 60 days. CONCLUSIONS: In this population of patients initiating DMD treatment within 2 years of MS diagnosis, mean time to first DMD was 112.6 days. Identifying factors associated with delayed treatment may provide better understanding of the reasons for delay, leading to improved disease management.

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.

Development and validation of a claims-based measure as an indicator for disease status in patients with multiple sclerosis treated with disease-modifying drugs.

BACKGROUND: Administrative healthcare claims data provide a mechanism for assessing and monitoring multiple sclerosis (MS) disease status across large, clinically representative "real-world" populations. The estimation of MS disease status using administrative claims can be a challenge, however, due to a lack of detailed clinical information. Retrospective claims analyses in MS have traditionally used rates of MS relapses to approximate disease status. Healthcare costs may be alternate, broader claims-based indicators of disease activity because costs reflect multiple facets of care of patients with MS, and there is a strong correlation between quality of life of patients with MS and costs of the disease. This study developed, tested, and validated a healthcare cost-based measure to serve as an indicator of overall disease status in patients with MS treated with disease-modifying drugs (DMDs) utilizing administrative claims. METHODS: Using IMS Health Real World Data Adjudicated Claims - US data (January 2006-June 2013), a negative binomial regression predicted annual all-cause medical costs. Coefficients reaching statistical significance (p < 0.05) and increasing costs by ≥5% were selected for inclusion into an MS-specific severity score (scale of 0 to 100). Components of the score included rehabilitation services, altered mental state, pain, disability, stiffness, balance disorder, urinary incontinence, numbness, malaise/fatigue, and infections. Coefficient weights represented each predictor's contribution. The predictive model was derived using 50% of a random sample and tested/validated using the remaining 50%. RESULTS: Average overall predicted annual total medical cost was $11,134 (development sample, n = 11,384, vs. $10,528 actual) and $11,303 (validation sample, n = 11,385, vs. $10,620 actual). The model had consistent bias (approximately +$600 or +6% of actual costs) for both samples. In the validation sample, mean MS disease status scores were 0.24, 8.95, and 21.77 for low, medium, and high tertiles, respectively. Mean costs were most accurately predicted among less severe patients ($5243 predicted vs. $5233 actual cost for lowest tertile). CONCLUSION: The algorithm developed in this study provides an initial step to helping understand and potentially predict cost changes for a commercially insured MS population.

An evaluation of adherence in patients with multiple sclerosis newly initiating treatment with a self-injectable or an oral disease-modifying drug.

OBJECTIVE: As the multiple sclerosis (MS) disease-modifying drug (DMD) treatment options have expanded to include oral therapies, it is important to understand whether route of administration is associated with DMD adherence. The objective of this study was to compare adherence to DMDs in patients with MS newly initiating treatment with a self-injectable versus an oral DMD. METHODS: This retrospective database study used IMS Health Real World Data Adjudicated Claims - US data between July 1, 2010 and June 30, 2014. Adherence was measured by medication possession ratio (MPR), calculated as the total number of treated days divided by the total number of days from the first treated day until the end of 12-month follow-up. A binary measure representing adherence (MPR ≥0.8) versus nonadherence (MPR <0.8) to therapy was used. Logistic regression evaluated the likelihood of adherence to index DMD type (self-injectable vs oral). Covariates included patient baseline characteristics (ie, age, sex, comorbidities) and index DMD type. RESULTS: The analysis included 7,207 self-injectable and 1,175 oral DMD-treated patients with MS. In unadjusted analyses, the proportion of patients adherent to therapy (MPR ≥0.8) did not differ significantly between the self-injectable (54.1%) and the oral DMD cohorts (53.0%; P=0.5075). After controlling for covariates, index DMD type was not a significant predictor of adherence (odds ratio [OR] 1.062; 95% confidence interval [CI]: 0.937-1.202; P=0.3473). Higher likelihood of adherence was associated with male sex (OR 1.20; 95% CI: 1.085-1.335; P=0.0005) and age groups older than 18-34 years (ORs 1.220-1.331; P<0.01). Depression was associated with a lower likelihood of adherence (OR 0.618; 95% CI: 0.511-0.747; P<0.0001). CONCLUSION: Male sex and age older than 18-34 years were significantly associated with a higher likelihood of adherence, while depression was associated with a lower likelihood of adherence. Index DMD type, stratified by the route of administration (self-injectable vs oral DMD), was not a significant predictor of DMD adherence.

Economic impact of hypoglycemia among insulin-treated patients with diabetes.

OBJECTIVE: The objective of this study was to assess the cost of hypoglycemic events among insulin-treated patients with diabetes and the potential cost savings to a hypothetical US health plan and employer of reducing hypoglycemic events with a device intervention. METHODS: A cost-calculator model was developed to estimate the direct costs of hypoglycemic events, accounting for diabetes type, age, and event severity. Model inputs were derived from published incidence rates of hypoglycemic events and direct medical costs. Assumed intervention efficacy was based on published studies of an emerging technology which yielded 72.2% (LGS Trial; ACTRN12610000024044) and 31.8% (ASPIRE Trial; NCT01497938) reductions in severe and non-severe hypoglycemic events, respectively. Model outcomes-including the number of severe (requiring medical assistance) and non-severe events, and direct/indirect medical costs (excluding intervention costs)-were evaluated over a 1-year period for a hypothetical health plan and employer perspectives. RESULTS: In a health plan with 10 million enrollees, patients without the intervention would have experienced 0.09 and 14.60 severe and non-severe hypoglycemic events per patient per year (PPPY), respectively (vs 0.02 severe and 9.96 non-severe events with the intervention). This translated into total direct medical cost savings of $45 million ($177 PPPY) for the health plan. For an employer with 100,000 employees, the intervention would have yielded additional savings of $492 PPPY in indirect costs. CONCLUSION: Insulin-treated patients experience hypoglycemic events, which are associated with substantial direct and indirect medical costs. The cost savings of reducing hypoglycemic events need to be weighed against the costs of using diabetes device interventions.

Patterns of Statin Use in a Real-World Population of Patients at High Cardiovascular Risk.

BACKGROUND: Widespread use of statins has improved hypercholesterolemia management, yet a significant proportion of patients remain at risk for cardiovascular (CV) events. Analyses of treatment patterns reveal inadequate intensity and duration of statin therapy among patients with hypercholesterolemia, and little is known about real-world statin use, specifically in subgroups of patients at high risk for CV events. OBJECTIVE: To examine patterns of statin use and outcomes among patients with high-risk features who newly initiated statin monotherapy. METHODS: Adult patients (aged > 18 years) at high CV risk who received > 1 prescription for statin monotherapy and who had not received lipid-modifying therapy during the previous 12 months were identified from the Truven MarketScan Commercial and Medicare Supplemental databases (from January 2007 to June 2013). Patients with atherosclerotic cardiovascular disease (ASCVD) or diabetes were hierarchically classified into 5 mutually exclusive CV risk categories (listed here in order from highest to lowest risk): (1) recent CV event (subcategorized by hospitalization for acute coronary syndrome [ACS] or other non-ACS CV event within 90 days of index); (2) coronary heart disease (CHD); (3) history of ischemic stroke; (4) peripheral artery disease (PAD); and (5) diabetes. Outcomes of interest included changes in therapy, proportion of days covered (PDC), time to discontinuation, and proportion of patients with ASCVD-related inpatient visit during the follow-up period. Statin therapy was subdivided into high-intensity treatment (atorvastatin 40 mg or 80 mg, rosuvastatin 20 mg or 40 mg, or simvastatin 80 mg) or moderate- to low-intensity treatment (all other statins and statin dosing regimens). Follow-up data were obtained from the index date (statin initiation) until the end of continuous enrollment. RESULTS: A total of 541,221 patients were included in the analysis. The majority of patients were stratified in the diabetes cohort (61.1%), followed in frequency by recent ACS event (15.8%), recent non-ACS CV event (9.9%), PAD (4.7%), CHD (4.4%), and history of ischemic stroke (4.1%). Only 15.0% of the population initiated therapy with a high-intensity statin, and 22.5% of these high-intensity statin initiators switched to a moderate- to low-intensity regimen during the follow-up period. Median time to statin discontinuation was approximately 15 months. Duration of treatment was longer among those who were treated with a high-intensity versus a moderate- to low-intensity statin regimen (21 and 15 months, respectively). The PDC was highest in the recent ACS hospitalization cohort (66.4%) and lowest in the diabetes cohort (55.5%). The PDC was significantly greater among patients who initiated treatment with a high-intensity statin regimen than with a moderate- to low-intensity statin regimen (62.1% vs. 57.5%, respectively; P< 0.001). At 1 year, Kaplan-Meier estimates of the cumulative rates for ASCVD-related hospitalizations ranged from 3.5% (diabetes) to 21.8% (recent ACS hospitalization). CONCLUSIONS: Patients at high risk for CV events are suboptimally dosed with statins, have high rates of discontinuation, and have low rates of adherence. Despite the use of statin therapy, ASCVD-related inpatient visit rates were high, particularly among those patients at highest risk because of a recent ACS hospitalization. Future interventions are required to ensure that high-risk patients are effectively managed to reduce subsequent morbidity and mortality. DISCLOSURES: Support for this research was provided by Regeneron Pharmaceuticals, Tarrytown, New York, and Sanofi US, Bridgewater, New Jersey. Menzin and Lin are employees of Boston Health Economics, which received consulting fees from Sanofi. Friedman is a consultant to Boston Health Economics. Lin, Friedman, and Menzin have received research support from Sanofi US. Sung, Mallya, Panaccio, and Koren are employees of Sanofi US and also have ownership interest in Sanofi US. Sanchez is an employee of and has ownership interest in Regeneron Pharmaceuticals. Neumann has served on advisory boards for Merck & Co, Takeda Pharmaceutical Company, Genentech, Novartis, Bayer AG, UCB, Sanofi US, Robert Wood Johnson Foundation, and Cubist and serves as consultant for Boston Health Economics, Forrest, P urdue, and Smith and Nephew. This research has been presented in part at the International Society for Pharmacoeconomics and Outcomes Research, 20th Annual International Meeting, May 16-20, 2015, Philadelphia, Pennsylvania. All authors contributed to the study design, protocol development, and results interpretation. Lin and Menzin were responsible for conducting the study analyses. All authors were involved in manuscript development and approved the submitted version.

Economic Evaluation of Linaclotide for the Treatment of Adult Patients With Chronic Idiopathic Constipation in the United States.

PURPOSE: To evaluate the effectiveness and costs of linaclotide (Linzess) versus lubiprostone (Amitiza) in the treatment of adult patients with chronic idiopathic constipation (CIC). DESIGN: A decision-tree model using model inputs derived from published literature, linaclotide phase 3 trial data, and a physician survey. METHODOLOGY: Measures of treatment efficacy were selected based on comparability between trial data, with posthoc analyses of linaclotide required to ensure comparability with available lubiprostone data. Response to therapy was defined as (1) having one of the best two satisfaction answers of a 5-point global treatment satisfaction scale at Week 4 or (2) having a weekly spontaneous bowel movement (SBM) frequency 4 at Week 4. Patients who do not respond to therapy are assumed to accrue costs associated with a treatment failure. Model time horizon is aligned with the lubiprostone clinical trial duration of 4 weeks. Model outputs include response rates, quality-adjusted life-years (QALYs) and direct costs. RESULTS: Linaclotide was associated with lower per-patient costs vs lubiprostone for both definitions of response ($946 vs $1,015 for global assessment and $727 vs $737 for SBM frequency). When treatment response was based on a global assessment of treatment satisfaction, linaclotide was associated with higher effectiveness (response: 39.3% vs 35.0%). For SBM frequency, linaclotide was slightly less effective compared to lubiprostone (response: 58.6% vs 59.6%), but also less costly. Base-case results were robust in sensitivity analysis. CONCLUSIONS: Linaclotide is less expensive with similar effectiveness when compared to lubiprostone for the treatment of CIC in adult patients.

Antithrombotic use and bleeding risk in patients with atrial fibrillation: findings from a multipayer analysis.

AIMS: To analyze administrative claims data from Medicaid, Medicare and commercial insurance sources to estimate stroke risk, bleeding risk, and the use of antithrombotic treatment in patients with atrial fibrillation (AF). METHODS: Included patients were aged ≥18 years with a new or existing diagnosis of AF. Outcomes were assessed over 1 year and included stroke risk (CHADS2/CHA2DS2-VASc score), bleeding risk (ATRIA score) and anticoagulant use. RESULTS: A total of 115,906 patients with AF met inclusion criteria between six databases. Among patients with high stroke risk (CHADS2 ≥2) and low bleeding risk (ATRIA 0-3), 42-82% did not receive an antithrombotic. CONCLUSION: Levels of thromboprophylaxis for high-risk AF patients in real-world data differ significantly from current medical guidelines for stroke prevention.

Prevalence of menopausal symptoms among mid-life women: findings from electronic medical records.

BACKGROUND: To assess the prevalence of menopausal symptoms among women prescribed hormone therapy (HT) using electronic medical record data from a regional healthcare organization. METHODS: Retrospective data from the Reliant Medical Group from 1/1/2006-12/31/2011 were assessed for 102 randomly-selected patients. Study eligibility criteria included: females aged 45 to 65; prescribed oral or transdermal HT; no history of breast cancer, venous thromboembolism, stroke, gynecological cancer, or hysterectomy; continuously enrolled in the health plan for 1 year before and after the first observed HT prescription. Prevalence of menopause-related symptoms was analyzed descriptively at both the patient and visit levels. RESULTS: Mean age of patients was 54 years. The most common menopausal symptoms were: hot flushes (40%), night sweats (17%), insomnia (16%), vaginal dryness (13%), mood disorders (12%), and weight gain (12%). Among the 102 patients, 163 individual visits listing menopausal symptoms were identified, of which hot flushes (71 visits) were the most common symptom identified. CONCLUSION: Our findings provide recent data on the types of menopausal symptoms experienced by mid-life women prescribed HT. Electronic medical records may be a rich source of data for future studies of menopausal symptoms in this population.

The impact of multimorbidity on quality of life among midlife women: findings from a U.S. nationally representative survey.

BACKGROUND: Little is known about the prevalence and cumulative burden of coexisting health conditions including chronic joint and muscular pain, urinary incontinence (UI), depression, osteoporosis risk, moderate/severe vasomotor symptoms, and vulvar/vaginal atrophy (VVA). We surveyed a nationally representative U.S. sample of midlife (age 40-64 years) women to ascertain the prevalence, general health-related quality of life (HRQoL), and health-seeking behaviors associated with these six conditions. METHODS: This cross-sectional, telephone survey collected data from a sample of English- and Spanish-speaking U.S. women. The survey contained demographic and menopausal status questions, and also five condition-specific symptom/disease risk-screening instruments. The EuroQol 5 dimensions (EQ-5D) questionnaire was used to measure HRQoL. Health-seeking behavior was measured based on clinician discussion of and recent treatment for each condition. RESULTS: Three thousand fifty eight women (mean age 53.4 years) completed the survey. The majority were white (75.6%), married (60.5%), employed full- or part-time (59.0%), and postmenopausal (69.8%; based on self-report). The prevalence [95% confidence interval] of 0, 1, 2, and ≥3 conditions was 35.2% [33.5-36.9], 34.2% [32.5-35.9], 17.9% [16.6-19.3], and 12.7% [11.5-13.9], respectively. Osteoporosis risk (30.6%) was most prevalent, followed by VVA (27.8%) and UI (26.6%). UI and VVA coexisted most frequently (11.3%), followed by osteoporosis risk and VVA (9.8%). EQ-5D scores decreased with increasing number of illnesses (0, 1, 2, and ≥3 conditions, means: 0.92, 0.87, 0.77, 0.61, respectively; p<0.01). Health-seeking behavior varied by condition. CONCLUSION: Over 25% of women surveyed had multiple coexisting conditions. Lower HRQoL was associated with multiple conditions and with each added condition.

Inhaled nitric oxide in term/late preterm neonates with hypoxic respiratory failure: estimating the financial impact of earlier use.

OBJECTIVE: We reported recently that early use of inhaled nitric oxide therapy (iNO) for term and late preterm infants with hypoxic respiratory failure (HRF) at an oxygenation index (OI) of ≥15 and <20 is associated with earlier discharge from the hospital, relative to babies treated at OI ≥25. The objective of the present analysis is to determine whether earlier use of iNO in this cohort leads to lower cost of medical care. METHODS: We used a decision-analytic model, which was developed to compare hospital resource use and costs associated with early versus standard use of iNO in HRF. The model population included infants with moderate HRF caused by primary pulmonary hypertension with an OI ≥15 and <20. A hypothetical case population of 1000 patients was assumed and probabilistic sensitivity analyses were completed where all the clinical inputs into the model were varied. Two deterministic sensitivity analyses were also completed, one surrounding the hospital cost inputs and another surrounding the cost of iNO. RESULTS: Early iNO was associated with fewer hospital days, fewer days of ventilation and fewer hours on extracorporeal membrane oxygenation (ECMO). In probabilistic sensitivity analyses, total costs per patient were $88,518 ± $7574 and $92,581 ± $9664 for early iNO and standard iNO, respectively. The probability of early iNO being cost-effective was approximately 72%, based on a willingness to pay $100,000 or less to prevent ECMO therapy and/or death. In both deterministic sensitivity analyses, early iNO was cost-saving. CONCLUSION: Our analysis shows that early use of iNO at an OI of ≥15 and <20 may be associated with shorter hospitalizations and a decreased cost of care for term/late preterm infants with HRF associated with pulmonary hypertension. Our results are based on clinical data from a single trial; future research using data from real-world practice is warranted.