Vismodegib Use in Clinical Practice: Analysis of a United States Medical Claims Database.

BACKGROUND: Information is limited on the use of vismodegib for treatment of advanced basal cell carcinoma beyond the setting of clinical trials. OBJECTIVE: To investigate the treatment patterns and characteristics of patients treated with vismodegib in clinical practice. METHODS: A longitudinal, retrospective cohort study was undertaken using data from a US commercial insurance claims (Truven Health Analytics MarketScan) database. Eligible patients were ≥18 years of age, with ≥1 claim for vismodegib from January 2012 to December 2015. RESULTS: A total of 321 patients were included in the analysis. Approximately 20% of the patients took 1 or more treatment breaks of ≥ 30 days each before treatment discontinuation. Median duration of vismodegib treatment before the first treatment break and discontinuation was 4.0 and 5.5 months, respectively. Older age ( > 65 years) and absence of Gorlin syndrome were associated with increased risk for treatment interruption or discontinuation. Overall, 47% and 36% of patients underwent surgery or radiotherapy within the 6 months before and after vismodegib initiation, respectively. CONCLUSIONS: Real-world evidence indicates that vismodegib is being used in clinical practice as part of combination treatment strategies. J Drugs Dermatol. 2018;17(2):143-148.

Cardiovascular, Kidney Failure, and All-Cause Mortality Events in Patients with Focal Segmental Glomerulosclerosis in a U.S. Real-World Database.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) leads to proteinuria and progressive decline in glomerular filtration rate which correlates with kidney failure and increased cardiovascular risk. The purpose of this study was to estimate the effects of proteinuria on kidney failure status/all-cause mortality and cardiovascular disease events/all-cause mortality, as well as the relationship between progression to kidney failure and occurrence of cardiovascular disease/mortality events among adult patients (≥18 years old) with FSGS. METHODS: This was an observational, retrospective cohort study utilizing Optum® de-identified Market Clarity Data and proprietary Natural Language Processing (NLP) data. The study period was from January 1, 2007 through March 31, 2021, with patients in the overall cohort being identified from July 1, 2007 through March 31, 2021. The index date was the first FSGS ICD-10 diagnosis code or FSGS-related NLP term within the identification period. RESULTS: Elevated proteinuria >1.5 g/g and ≥3.5 g/g increased risk for kidney failure/all-cause mortality (adjusted hazard ratio [95% CI]: 2.34 [1.99-2.74] and 2.44 [2.09-2.84], respectively) and cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 2.11 [1.38-3.22] and 2.27 [1.44-3.58], respectively). Progression to kidney failure was also associated with a higher risk of cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 3.04 [2.66-3.48]. CONCLUSIONS: A significant proportion of FSGS patients experience kidney failure and cardiovascular disease events. Elevated proteinuria and progression to kidney failure were associated with a higher risk of cardiovascular disease/all-cause mortality events, and, elevated pre-kidney failure proteinuria was associated with progression to kidney failure/all-cause mortality events. Treatments that meaningfully reduce proteinuria and slow the decline in glomerular filtration rate have the potential to reduce the risk of cardiovascular disease, kidney failure and early mortality in patients with FSGS.

Healthcare resource utilization and costs among patients with post-stroke spasticity before and after spasticity management including onabotulinumtoxina.

BACKGROUND: Real-world data regarding the impact of onabotulinumtoxinA on healthcare resource utilization and costs for post-stroke spasticity are scarce. OBJECTIVE: To compare differences in 12-month healthcare resource utilization and costs before and after post-stroke spasticity management including onabotulinumtoxinA. METHODS: This retrospective claims analysis of IBM MarketScan Commercial and Medicare Supplemental databases included adults with ≥ 1 onabotulinumtoxinA claim for post-stroke spasticity (1 January 2010 to 30 June 2018) and continuous enrolment for ≥ 12 months pre- and post-index (first onabotulinumtoxinA claim date). All-cause and spasticity-related healthcare resource utilization and costs were compared 12 months pre- and post-index (McNemar's χ2 test or paired t-test). A subgroup analysis assessed effect of stroke-to-index interval on costs. RESULTS: Among 735 patients, mean (standard deviation) stroke-date-to-index-date interval was 284.5 (198.8) days. Decreases were observed post-index for mean all-cause outpatient (62.9 vs 60.5; p ≤ 0.05) and emergency department visits (1.1 vs 0.8; p ≤ 0.0001), and hospital admissions (1.5 vs 0.4; p ≤ 0.0001). Increase in prescription fills (43.0 vs 53.7) was seen post-index. Post-index decreases in all-cause (-66%) and spasticity-related (-51%) costs were driven by reduced inpatient care costs. Findings were consistent regardless of stroke-date-to-index-date interval. CONCLUSION: Significant reductions in healthcare resource utilization and costs were observed after 1 year of post-stroke spasticity management including onabotulinumtoxinA. Long-term studies are needed to establish causality.

Impact of Proteinuria and Kidney Function Decline on Health Care Costs and Resource Utilization in Adults With IgA Nephropathy in the United States: A Retrospective Analysis.

Rationale & Objective: Among patients with IgA nephropathy (IgAN), proteinuria and decline in kidney function may be associated with increased economic burden. This study aimed to provide current information on the epidemiology and economic burden of IgAN in the United States. Study Design: Retrospective cohort study. Setting & Study Population: Overall, 9,984 patients in the Optum's Market Clarity database identified by the presence of at least 2 natural language processing-derived IgAN signs and disease and symptoms terms; 813 with linked claims data included in a health care resource utilization/cost subcohort. Predictor: High-risk proteinuria (≥1 g/d), chronic kidney disease (CKD) stage. Outcomes: Standardized prevalence, health care resource utilization, costs. Analytical Approach: Descriptive statistics for categorical and continuous variables. Direct standardization for prevalence estimation. Generalized linear models for health care resource utilization/costs, reported as per-patient-per-month (PPPM) costs in 2020 US dollars. Results: The estimated standardized US prevalence of IgAN (2016-2020) was 329.0 per 1,000,000 persons. High-risk proteinuria (≥1 vs <1 g/d) was associated with a higher mean PPPM number of outpatient visits (3.49 vs 1.74; P = 0.01) and pharmacy claims (3.79 vs 2.41; P = 0.01), contributing to higher mean total costs PPPM ($3,732 vs $1,457; P = 0.01). Furthermore, higher CKD stage was also associated with higher health care resource utilization (number of outpatient visits PPPM, number of pharmacy claims PPPM, proportion of patients with inpatient visits and emergency department visits; P < 0.001) and mean total cost PPPM (from $2,111 CKD stage 1 to $10,703 CKD stage 5/kidney failure; P < 0.001). Limitations: Generalizability outside of the catchment group for the database, missing data/errors inherent in retrospective database studies, relatively small sample size, use of Optum Market Clarity standardized pricing algorithms, exclusion of out-of-pocket costs. Conclusions: Health care resource utilization and costs were higher for IgAN patients with high-risk proteinuria and worsening kidney function. Treatments that reduce proteinuria and slow CKD disease progression may reduce the economic burden associated with IgAN. Plain-Language Summary: Immunoglobulin A nephropathy (IgAN) is a rare kidney disease. Over time, the kidneys may leak protein into the urine (proteinuria). IgAN can lead to kidney failure. Because IgAN is rare, it is hard to know how many people have it. This study used electronic health records to estimate the number of patients with IgAN in the United States, describe the characteristics of patients, and understand their treatments and the costs. The number of patients with IgAN increased between 2016 and 2020. The researchers think this is because doctors learned more about IgAN. Patients with severe disease used more health care resources and had higher costs. The authors believe treatments that slow kidney damage may reduce the cost of treating IgAN.

Place of care and costs associated with acute episodes and remission in bipolar I disorder.

AIMS: To our knowledge, literature describing the place of care and associated costs during acute bipolar I disorder (BP-I) episodes is limited. We conducted a claims-based retrospective study to address this gap. MATERIALS AND METHODS: Adults with BP-I were identified via IBM MarketScan Commercial and Medicare Supplemental databases. The acute episode index date was defined by ≥1 inpatient BP-I claim(s) or ≥1 outpatient or ≥3 outpatient BP-I claims (depending on visit type) in a 2-week (manic/mixed) or 4-week (depressive) period. Likely acute episodes were defined as 3- and 6-week periods for manic/mixed and depressive episodes, respectively; total mental health-related medical costs (health plan + patient) were collected during these intervals and stratified by setting (inpatient versus outpatient). Initial and subsequent episodes were captured; data were reported in subgroups without and with clozapine use, a proxy for disease severity. The remission index date was the earliest outpatient claim with a bipolar remission diagnosis with no acute episode or treatment. Remission costs were collected over a 3-month period. All results were analyzed descriptively. RESULTS: A total of 41,516 patients with 130,221 acute manic/mixed episodes and 47,763 patients with 149,207 acute depressive episodes met the study criteria. Over 84% of acute episodes were treated in outpatient settings. Mental health-related medical costs for manic/mixed episodes were $15,444 for inpatient and $1,577 for outpatient settings; inpatient and outpatient costs for depressive episodes were $17,376 and $2,154, respectively. Health plans covered approximately 78% of medical costs for both episode types with and without prior clozapine use. A total of 8,143 patients met remission criteria; the total 3-month outpatient costs were $1,225. CONCLUSIONS: Most BP-I acute manic/mixed or depressive episodes were treated in the outpatient setting. Episodes with inpatient care were 8-10 times more costly than outpatient-only episodes. Health plans covered most medical costs, but additional patient-incurred out-of-pocket costs remained.

Persistence with daily growth hormone among children and adolescents with growth hormone deficiency in the UK.

Background: Children with growth hormone deficiency (GHD) are treated with daily somatropin injections; however, poor treatment persistence and adherence have been recognized previously and have been shown to negatively impact growth outcomes. A recent real-world study of a US pediatric GHD population found that a substantial proportion of children discontinued somatropin therapy, but similar data for a real-world UK population are lacking. Objectives: To describe the discontinuation of, and persistence with, daily somatropin treatment among children with GHD in the UK. Methods: This was a retrospective cohort study of children (≥3 and <16 years old) with ≥1 medication prescription for daily injectable somatropin from 1 July 2000 to 31 December 2020 in the IQVIA Medical Research DATA (IMRD) database. Early persistence was defined as the proportion of children prescribed ≥1 somatropin refill (≥2 prescriptions). Discontinuation was defined as the first date at which a medication gap for somatropin (of >60 or >90 days between prescriptions) occurred. Kaplan-Meier methods were used to evaluate persistence (non-discontinuation) over time to assess time to first discontinuation event. Cox proportional hazards models were used to evaluate the relationship between patient characteristics and time to medication discontinuation. Results: Among the cohort identified in this study (n = 117), the majority (n = 84, 71.8%) had 48 months of available follow-up; 56.4% were boys and the mean (median) age was 8.6 (8.0) years. About 98% exhibited early persistence, but persistence over the follow-up period decreased with follow-up duration. Using the conservative 90-day gap definition of persistence, an estimated 72.4%, 52.8%, and 43.3% were persistent at 12, 36, and 48 months. Lower persistence rates were observed using the 60-day definition. No significant patient predictors of time to discontinuation were identified. Conclusions: Despite high early persistence with somatropin, a high percentage of children with GHD were increasingly non-persistent over time. More than 1 in 4 were non-persistent at 12 months and more than 1 in 2 were non-persistent at 48 months of follow-up. These results suggest that strategies to support improved medication-taking behavior among children with GHD in the UK are warranted.

Neuropsychiatric comorbidities in Huntington's and Parkinson's Disease: A United States claims database analysis.

OBJECTIVE: Huntington's disease is a rare, genetic, neurodegenerative disease characterized by a triad of cognitive, behavioral, and motor symptoms. The condition gradually results in increasing disability, loss of independence, and ultimately death. Our objective was to use United States claims data (which offer valuable insight into the natural history of disease) to compare the prevalent comorbidities of people with Huntington's disease against matched controls with Parkinson's disease or with no major neurodegenerative diseases (general population controls). We also assess medication use in people with Huntington's disease. METHODS: This was a retrospective, observational study using data from the IBM MarketScan® Databases. Cases and controls were matched 1:1, and comorbidities were analyzed in each group during 2017. Medications were also assessed in the Huntington's disease cohort. Eligible cases had ≥ 2 diagnostic codes for Huntington's disease; controls had ≥ 2 codes for Parkinson's disease (with no record of Huntington's disease), or, for general population controls, no record of Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, or dementia. RESULTS: A total of 587 matched individuals were assessed in each cohort. Depression and anxiety were more common in Huntington's disease versus Parkinson's disease (odds ratios: 1.51 and 1.16, respectively). Other conditions more common in Huntington's disease included dementia, communication/speech problems, dysphagia, and falls. The use of antidepressant (59.9%) and antipsychotic (39.5%) medications was frequent among Huntington's disease cases. INTERPRETATION: These data highlight the prevalence of psychiatric, cognitive, communication, swallowing, and mobility problems in people with Huntington's disease, underscoring the need for holistic expert care of these individuals.

Health care resource utilization and costs associated with nonadherence and nonpersistence to antidepressants in major depressive disorder.

BACKGROUND: Nonadherence and nonpersistence to antidepressants in major depressive disorder (MDD) are common and associated with poor clinical and functional outcomes and increased health care resource utilization (HCRU) and costs. However, contemporary real-world evidence on the economic effect of antidepressant nonadherence and nonpersistence is limited. OBJECTIVE: To assess the effect of nonadherence and nonpersistence to antidepressants on HCRU and costs in adult patients with MDD enrolled in U.S. commercial and Medicare supplemental insurance plans. METHODS: This was a retrospective new-user cohort study using administrative claims data from the IBM MarketScan Commercial and Medicare Supplemental databases from January 1, 2010, to December 31, 2018. We identified adult patients with MDD aged ≥ 18 years who initiated antidepressant therapy for a new MDD episode between January 1, 2011, and December 31, 2017. Twelve-month total all-cause HCRU and costs (2019 U.S. dollars) were characterized for patients who were adherent/nonadherent and persistent/nonpersistent to antidepressants at 6 months. Adherence was defined as having proportion of days covered (PDC) ≥ 80%, and persistence was defined as having continuous antidepressant therapy without a ≥ 30-day gap. Multivariable negative binomial regression and 2-part models adjusted for baseline characteristics were used to estimate incidence rate ratios (IRRs) for HCRU and incremental costs of nonadherence and nonpersistence, respectively. RESULTS: A total of 224,645 patients with MDD (commercial: n = 209,422; Medicare supplemental: n = 15,223) met all study inclusion criteria. Approximately half of patients were nonadherent (commercial: 48%; Medicare supplemental: 50%) or nonpersistent (commercial: 49%; Medicare supplemental: 52%) to antidepressants at 6 months. After controlling for baseline characteristics, nonadherent patients experienced significantly more inpatient hospitalizations (commercial, adjusted IRR [95% CI]: 1.34 [1.29 to 1.39]; Medicare supplemental: 1.19 [1.12 to 1.28]) and emergency room (ER) visits (commercial, adjusted IRR [95% CI]: 1.43 [1.40 to 1.45]; Medicare supplemental: 1.28 [1.21 to 1.36]) compared with adherent patients. Similar results were observed in nonpersistent patients. Adjusted mean differences revealed that nonadherent and nonpersistent patients accumulated significantly higher medical costs (commercial: $568 [95% CI: $354 to $764] and $491 [$284 to $703]; Medicare supplemental: $1,621 [$314 to $2,774] and $1,764 [$451 to $2,925]), inpatient costs (commercial: $650 [$490 to $801] and $564 [$417 to $716]; Medicare supplemental: $1,546 [$705 to $2,308] and $1,567 [$778 to $2,331]), and ER costs (commercial: $130 [$115 to $143] and $129 [$115 to $142]; Medicare supplemental: $82 [$23 to $150] and $80 [$18 to $150]), and incurred significantly lower pharmacy costs (commercial: -$561 [-$601 to -$521] and -$576 [-$616 to -$540]; Medicare supplemental: -$510 [-$747 to -$227] and -$596 [-$830 to -$325]) compared with adherent and persistent patients, respectively. CONCLUSIONS: This study found more hospitalizations and ER use and higher total medical costs among patients who were nonadherent and nonpersistent to antidepressants at 6 months. Strategies that promote better adherence and persistence may lower HCRU and medical costs in patients with MDD. DISCLOSURES: This study was sponsored by Allergan, which was involved in the study design; data collection, analysis, and interpretation of data; and decision to present these results. Ta was supported by a training grant provided to the University of Washington by Allergan at the time this study was conducted. Tung and Gillard are employees of Allergan. Oliveri is an employee of Genesis Research. Sullivan and Devine have no financial disclosures. This study was presented as a poster at AMCP 2020 (Virtual Meeting), April 21-24, 2020.

The association of timing of disease-modifying drug initiation and relapse in patients with multiple sclerosis using electronic health records.

OBJECTIVE: A large, US de-identified electronic health record (EHR) database (Optum-Humedica de-identified Electronic Health Record dataset) was used to evaluate whether earlier disease-modifying drug (DMD) treatment initiation was associated with improved outcomes in multiple sclerosis (MS). METHODS: Newly diagnosed patients from 1 January 2008 to 30 August 2014 (International Classification of Diseases, Ninth Revision, Clinical Modification code: 340.xx; first MS diagnosis = index date) with healthcare activity 1 year pre- and 2 years post-index, and who initiated DMD treatment during the 2 year follow-up period, were included. Patients were categorized as Early or Late Initiators (initiated DMD treatment ≤90 or >90 days following index, respectively). Relapse was determined by the presence of an MS-related hospitalization or an outpatient encounter with MS diagnosis and corticosteroid prescription within 7 days. RESULTS: A total of 4732 patients met the inclusion criteria: 2042 (43.2%) were Early Initiators and 2690 (56.8%) were Late Initiators. Similar baseline mean age (46.9 years for both cohorts) and Charlson Comorbidity Index scores (Early Initiators: 0.3, Late Initiators: 0.32) were observed. Average time to treatment was 20.9 ± 27.6 days for Early Initiators and 346.3 ± 181.1 days for Late Initiators. A significantly higher proportion of Late Initiators (n = 609; 22.6%) had a relapse during the 2 years following MS diagnosis compared with Early Initiators (n = 403; 19.7%; p = .0158). After controlling for covariates using multivariable logistic regression, late initiation of DMD treatment was associated with greater likelihood of relapse compared with early initiation (odds ratio 1.189; 95% CI: 1.031-1.371; p = .0172). CONCLUSIONS: Later initiation of DMD treatment (i.e. >90 days after MS diagnosis) in patients with MS was associated with a greater likelihood of relapse compared with earlier initiation. Early initiation of DMD treatment following a diagnosis of MS may have an effect on long-term outcomes.