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Introduction: Spinal muscular atrophy (SMA) is a rare, genetic neuromuscular disorder caused by deletion/mutation of the survival motor neuron 1 gene, characterized by progressive loss of motor neurons, resulting in increasing muscular weakness, deteriorating motor function, and, in its most severe form, death before 2 years. Nusinersen, an antisense oligonucleotide that increases expression of the functional SMN protein, was approved for SMA by US and European regulatory agencies in 2016 and 2017, respectively. The indicated regimen requires intrathecal injections every 4 months, following the first four injections during the loading phase. Adherence is integral to treatment success. Adherence to nusinersen may pose particular challenges as most patients with SMA are young children who require complex multidisciplinary care (including ongoing intrathecal treatment administration and potential specialized anesthetic and surgical procedures) at specialized centers. However, real-world data on adherence to nusinersen are limited., Methods: We conducted a retrospective claims database analysis from December 23, 2016, to November 20, 2019, to study nusinersen adherence and discontinuation/persistence in US patients with SMA types 1-3 who completed the loading phase, and to determine the impact of non-adherence or treatment discontinuation on SMA-related comorbidities, health care resource utilization (HCRU), and costs., Results: We identified 23 patients with SMA type 1, 41 patients with SMA type 2, and 260 patients with SMA type 3 who had completed the loading phase. Deviations from the indicated nusinersen treatment schedule were frequent in real-world usage, with most patients receiving ≥1 dose outside the scheduled interval. Across SMA types, non-adherent patients were more likely to have had SMA-related comorbidities (e.g., feeding difficulties, dyspnea and respiratory anomalies, and muscle weakness) and greater HCRU. Persistence rates 12 months after treatment initiation for patients with SMA types 1, 2, and 3 were 55.2%, 42.4%, and 54.6%, respectively. Patients who discontinued nusinersen and those who did not had generally similar comorbidity profiles. Discontinuation was associated with greater health care costs across SMA types., Conclusion: Our analysis of claims data indicated that discontinuation and non-adherence to nusinersen treatment were prevalent, and associated with greater frequency of comorbidities, greater HCRU, and increased costs for patients., (© 2021. The Author(s).)

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia due to chronic kidney disease (CKD). In addition to drug acquisition costs, the administration of ESAs can include direct and indirect costs due to the needle-based route of administration (eg, time spent by health care staff administering therapy, and patients' and caregivers' time spent receiving or assisting with therapy). However, a comprehensive assessment of the costs associated with the administration of ESAs is lacking. OBJECTIVE: To estimate the excess costs associated with the needle-based administration of ESAs for the treatment of anemia due to non-dialysis-dependent (NDD) CKD in the United States in 2019 from a societal perspective. METHODS: Excess costs associated with ESA administration were estimated as the sum of annual costs that could be avoided with the introduction of an oral treatment with comparable safety and efficacy to ESAs. Cost components included direct health care costs, transportation costs, and work productivity loss costs from the perspective of both patients and caregivers (as applicable). Costs were estimated based on scientific publications, governmental agencies, and the results of a recent survey of US patients and caregivers of patients with anemia and CKD. The setting of the administration (ie, at home vs in clinic), frequency of administration, and insurance type were considered. RESULTS: At the societal level, annual excess costs associated with ESA administration were estimated at $2.5 billion in the United States in 2019, based on an estimated 462,005 patients with anemia and NDD-CKD treated with ESAs. Overall, 94.4% ($2.4 billion) of these costs were incurred from in-clinic ESA administration. When stratifying costs by insurance type, Medicare-insured patients accounted for 79.4% ($2.0 billion) of total annual excess costs. The largest contributor to total annual excess costs was direct health care costs ($1.4 billion, 54.9%), followed by patient work productivity loss costs ($846 million, 33.9%), caregiver work productivity loss costs ($197 million, 7.9%), and transportation costs ($81 million, 3.3%). Total annual excess costs of in-clinic administration ranged from $2,572 per patient receiving monthly administration to $20,948 per patient receiving thrice-weekly administration, while the total annual excess costs of at-home administration ranged from $1,123 per patient receiving monthly administration to $2,109 per patient receiving thrice-weekly administration. At the ESA administration level (ie, for each ESA administration), total excess costs were estimated at $128 per in-clinic ESA administration and $7 per at-home ESA administration, excluding monitoring costs. CONCLUSIONS: The needle-based administration of ESAs in patients with NDD-CKD is associated with a substantial economic burden. The introduction of an oral treatment has the potential to result in important cost savings from a societal perspective. DISCLOSURES : This study was funded by Otsuka Pharmaceutical Development & Commercialization, Inc., and Akebia Therapeutics, Inc. The study sponsors participated in the study design, data collection, analysis, interpretation of the data, writing of the report, and in the decision to submit the manuscript for publication. Gauthier-Loiselle, Cloutier, Serra, Bungay, and Guérin are employees of Analysis Group, Inc., a consulting firm that received funding from Otsuka Pharmaceutical Development & Commercialization, Inc., for the conduct of this study. Michalopoulos was an employee of Otsuka Pharmaceutical Development & Commercialization, Inc., at the time the study was conducted. Szabo is an employee of Akebia Therapeutics, Inc.

Nephrology nurses face health and wellness challenges due to significant work-related stressors. This survey, conducted online between July 24 and August 17, 2020, assessed the psychological well-being of nephrology nurses in the United States during the COVID-19 pandemic (n = 393). Respondents reported feeling burned out from work (62%), symptoms of anxiety (47% with Generalized Anxiety Disorder-7 [GAD-7] scores ≥ 5), and major depressive episodes (16% with Patient Health Questionnaire-2 [PHQ-2] scores ≥ 3). Fifty-six percent (56%) of survey respondents reported caring for COVID-19 patients, and 62% were somewhat or very worried about COVID-19. Factors, including high workload, age, race, and the COVID-19 pandemic, may partially explain the high proportion of nephrology nurses who reported symptoms of burnout, anxiety, and depression., (Copyright© by the American Nephrology Nurses Association.)

Objective: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease that often follows pulmonary embolism (PE). Screening for CTEPH is challenging, often delaying diagnosis and worsening prognosis. Predictive risk models for CTEPH could help identify at-risk patients, but existing models require multiple clinical inputs. We developed and validated a predictive risk model for CTEPH using health insurance claims that can be used by payers/quality-of-care organizations to screen patients post-PE., Methods: Adult patients newly diagnosed with acute PE (index date) were identified from the Optum De-identified Clinformatics Extended DataMart (January 2007-March 2018; development set) and IBM MarketScan (January 2008-June 2019; validation set) databases. Predictors were identified 12 months before or on the index PE. Risk of "likely CTEPH" was assessed post-PE based on CTEPH-related diagnoses and procedures since the CTEPH diagnosis code (ICD-10-CM: I27.24) was not available until 1 October 2017. Stepwise variable selection was used to build the model using the development set; model validation was subsequently conducted using the validation set., Results: The development set included 93,428 patients, of whom 11,878 (12.7%) developed likely CTEPH. Older age (odds ratios [OR] = 1.16-1.49), female (OR = 1.09), unprovoked PE (i.e. without thrombotic factors; OR = 1.14), hypertension (OR = 1.07), osteoarthritis (OR = 1.08), diabetes (OR = 1.07), chronic obstructive pulmonary disease (OR = 1.11), obesity (OR = 1.21) were associated with higher odds of likely CTEPH, and oral anticoagulants with lower odds (OR= 0.50, all p  < .01). C-statistic was 0.77 in the development and validation sets., Conclusion: A claims-based risk model reliably predicted the risk of CTEPH post-PE and could be used to identify high-risk patients who may benefit from focused monitoring.

Objectives: To evaluate geographic variation in the prevalence of autosomal dominant polycystic kidney disease (ADPKD) in the US, including ADPKD at risk of rapid progression., Methods: Claims data from the IBM MarketScan Commercial and Medicare Supplemental databases (01/16/2016-12/31/2017) were used to estimate the 2017 annual and 2016-2017 two-year prevalence of diagnosed ADPKD and ADPKD at risk of rapid progression in the US overall, and stratified by census regions and states. Risk of rapid progression was identified based on either: hypertension <35 years, hematuria <30 years, albuminuria, stage 2 chronic kidney disease (CKD) <30 years, stage 3 CKD <50 years, and stage 4/5 CKD or kidney transplant <55 years., Results: Annual prevalence was estimated at 2.34 and two-year prevalence at 3.61 per 10,000 in the US. Across census regions, two-year prevalence per 10,000 was highest in the Northeast (4.14) and lowest in the West (3.35). Prevalence was significantly correlated with the proportion of individuals in urban areas ( r  = .34, one-sided p  = .026). In 2017, 37.5% of patients were identified as being at risk for rapid progression, and this proportion was larger among patients in the South (42.1%, p  < .001)., Conclusion: This estimate for ADPKD prevalence is consistent with previously reported national estimates, with regional variation suggesting that ADPKD might be under-diagnosed in rural areas with more limited access to care. More than one-third of ADPKD patients presented risk factors associated with rapid progression, highlighting the need for timely identification, as disease-modifying therapy may delay progression to end-stage renal disease.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited kidney diseases characterized by progressive development of renal cysts and numerous extra-renal manifestations, eventually leading to kidney failure. Given its chronic and progressive nature, ADPKD is expected to carry a substantial economic burden over the course of the disease. However, there is a paucity of evidence on the impact of ADPKD from a societal perspective. This study aimed to estimate the direct and indirect costs associated with ADPKD in the United States (US)., Methods: A prevalence-based approach using data from scientific literature, and governmental and non-governmental organizations was employed to estimate direct healthcare costs (i.e., medical services, prescription drugs), direct non-healthcare costs (i.e., research and advocacy, donors/recipients matching for kidney transplants, transportation to/from dialysis centers), and indirect costs (i.e., patient productivity loss from unemployment, reduced work productivity, and premature mortality, caregivers' productivity loss and healthcare costs). The incremental costs associated with ADPKD were calculated as the difference between costs incurred over a one-year period by individuals with ADPKD and the US population. Sensitivity analyses using different sources and assumptions were performed to assess robustness of estimates and account for variability in published estimates., Results: The estimated total annual costs attributed to ADPKD in 2018 ranged from $7.3 to $9.6 billion in sensitivity analyses, equivalent to $51,970 to $68,091 per individual with ADPKD. In the base scenario, direct healthcare costs accounted for $5.7 billion (78.6%) of the total $7.3 billion costs, mostly driven by patients requiring renal replacement therapy ($3.2 billion; 43.3%). Indirect costs accounted for $1.4 billion (19.7%), mostly driven by productivity loss due to unemployment ($784 million; 10.7%) and reduced productivity at work ($390 million; 5.3%). Total excess direct non-healthcare costs were estimated at $125 million (1.7%)., Conclusions: ADPKD carries a considerable economic burden, predominantly attributed to direct healthcare costs, the majority of which are incurred by public and private healthcare payers. Effective and timely interventions to slow down the progression of ADPKD could substantially reduce the economic burden of ADPKD.

Objective: To develop and validate models allowing the prediction of major adverse chronic renal outcomes (MACRO) in patients with type 2 diabetes mellitus (T2DM) using insurance claims data. Methods: The Optum Integrated Real World Evidence Electronic Health Records and Claims de-identified database (10/01/2006-09/30/2016) was used to identify T2DM patients ≥50 years old. Risk factors were assessed over a 12-month baseline period, and MACRO were subsequently assessed until the end of data availability, continuous enrollment, or death. Separate models were built for moderate-to-severe diabetic kidney disease (DKD), end-stage renal disease (ESRD), and renal death. A random split-sample approach was employed, where 70% of the sample served for model development (training set) and the remaining 30% served for validation (testing set). C-statistics were used to assess model performance. Results: A total of 160,031 patients were included. Risk factors associated with MACRO for all models included adapted diabetes complications severity index, heart failure, anemia, diabetic nephropathy, and CKD. C-statistics ranged between 0.70 (moderate-to-severe DKD) and 0.84 (renal death) in the testing set. A substantial proportion (e.g. 88.7% for moderate-to-severe DKD) of patients predicted to be at high-risk of MACRO did not have diabetic nephropathy, proteinuria, or CKD at baseline. Conclusions: The models developed using insurance claims data could reliably predict the risk of MACRO in patients with T2DM and enabled patients at higher-risk of DKD to be identified in the absence of baseline diabetic nephropathy, CKD, or proteinuria. These models could help establish strategies to reduce the risk of MACRO in T2DM patients.

Aims: To estimate healthcare resource utilization (HRU) and costs among patients with spinal muscular atrophy (SMA) type 1 (SMA1) in real-world practice, overall and among patients treated with nusinersen. As a secondary objective, HRU and costs were estimated among patients with other SMA types (i.e. 2, 3, or 4 combined), overall and among patients treated with nusinersen. Materials and methods: Patients with SMA were identified from the Symphony Health's Integrated Dataverse (IDV) open claims database (September 1, 2016-August 31, 2018) and were classified into four cohorts based on SMA type and nusinersen treatment (i.e. SMA1, SMA1 nusinersen, other SMA, and other SMA nusinersen cohorts). The index date was the date of the first SMA diagnosis after December 23, 2016 or, for nusinersen cohorts, the date of nusinersen initiation. The study period spanned from the index date to the earlier among the end of clinical activity or data availability. Results: Patients in the SMA1 ( n  = 349) and SMA1 nusinersen ( n  = 45) cohorts experienced an average of 59.4 and 56.6 days with medical visits per-patient-per-year (PPPY), respectively, including 14.1 and 4.6 inpatient days. Excluding nusinersen-related costs, total mean healthcare costs were $137,627 and $92,618 PPPY in the SMA1 and SMA1 nusinersen cohorts, respectively. Mean nusinersen-related costs were $191,909 per-patient-per-month (PPPM) for the first 3 months post-initiation (i.e. loading phase) and $36,882 PPPM thereafter (i.e. maintenance phase). HRU and costs were also substantial among patients in the other SMA ( n  = 5,728) and other SMA nusinersen ( n  = 404) cohorts, with an average of 44.5 and 63.7 days with medical visits PPPY and total mean healthcare costs (excluding nusinersen-related costs) of $49,175 and $76,371 PPPY, respectively. Limitations: The database may contain inaccuracies or omissions in diagnoses, procedures, or costs, and does not capture medical services outside of the IDV network. Conclusions: HRU and healthcare costs were substantial in patients with SMA, including in nusinersen-treated patients.

Background: Few studies have examined patient characteristics and treatment patterns among patients with dementia and agitation in the United States (US)., Objective: To examine real-world treatment patterns and characteristics of patients with agitation related to dementia who were treated with antipsychotics in US residential care and community-based settings., Methods: This retrospective chart review collected US physician-level data from patients 55 to 90 years old initiated on an antipsychotic medication for the treatment of agitation related to dementia from January 2018 to May 2018. Clinical characteristics and treatment patterns were assessed overall and stratified by residential care and community-based settings., Results: A total of 313 participating physicians, 59.5% of whom were primary care physicians, abstracted 801 patient charts (residential care: n = 312; community-based: n = 489). Of patients with agitation who were initiated on an antipsychotic, most patients (74.5%) were initiated within 3 months of the onset of their studied agitation episode, and 62.8% experienced multiple agitation episodes before initiation. While non-pharmacological therapies are recommended first-line approach for agitation in dementia, use of non-pharmacological therapy before initiation of antipsychotics was reported for only 37.8% of patients in residential care and 21.3% in community-based settings., Conclusion: Most patients were initiated on an antipsychotic treatment after multiple episodes of agitation and largely without initial non-pharmacological therapy, suggesting that current treatment guideline recommendations for first-line non-pharmacological intervention may not be adequately followed in clinical practice. Understanding the clinical burden and treatment patterns among dementia patients with agitation is imperative for effective disease management.

Background: Nocturia, characterized as waking during the main sleep period to urinate, is a common condition. Persistent nocturia results in sleep fragmentation with deleterious effects on health and well-being. Yet, there are limited data on the economic burden of nocturia in the United States., Objective: To assess the association of nocturia with health care resource utilization (HRU), work productivity, and self-rated health while estimating the societal costs of nocturia in the United States in 2017., Methods: A retrospective cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES; 2005-2006 to 2013-2014). Adults aged ≥ 18 years (excluding pregnant women) were stratified into individuals with nocturia (≥ 2 voids/night) and individuals without nocturia (< 2 voids/night), based on the threshold for clinically significant nocturia. Outcomes were self-reported and included HRU (hospitalizations, outpatient visits); work productivity (weekly hours worked, employment); and current health status. Multivariable regression analyses adjusting for age, race, sex, body mass index, insurance status, education level, alcohol use, smoking status, and self-reported comorbid conditions were used to compare the 2 cohorts, overall and stratified by age group (20-44 years, 45-64 years, and 65+ years) to distinguish the effects on different age groups including the Medicare-aged population. Excess direct health care costs and indirect productivity costs associated with nocturia in the United States were then calculated using a prevalence-based approach and available literature (i.e., nocturia prevalence estimates, aggregated unit costs by HRU type, and average hourly earnings in the United States)., Results: 22,300 individuals were identified, and 24% had nocturia (≥ 2 voids/night). Median age was 55.2 and 43.2 years among individuals with and without nocturia, respectively, and the proportion of males was 43.3% and 51.3%, respectively. Individuals with nocturia had significantly more HRU, including hospitalizations and outpatient visits, worked significantly fewer hours weekly, and were significantly less likely to be employed when compared with those without nocturia. They were also significantly less likely to report being in very good/excellent health. These comparisons remained statistically significant across age groups. Total excess direct health care costs were $62.9 billion (hospitalization: $47.6 billion; outpatient: $15.3 billion). Total excess indirect productivity costs were $151.7 billion. Altogether, costs were estimated at $214.5 billion, equivalent to $3,491 per individual with nocturia. Individuals aged 20-44 years incurred 23.5% of total excess costs, while those aged 45-64 and 65+ years incurred 48.2% and 28.3%, respectively. Sensitivity analyses based on lower prevalence estimates resulted in costs of $94.0 billion, while those based on higher prevalence estimates reached up to $231.1 billion., Conclusions: Nocturia is associated with a substantial economic burden in the United States even when evaluated based on lower prevalence estimates. This study underscores the importance of timely diagnosis and management of nocturia patients to alleviate health-related and economic consequences to patients and society., Disclosures: This work was supported by Ferring Pharmaceuticals, which contributed to and approved the study design and participated in the interpretation of data, review, and approval of the manuscript. Gauthier-Loiselle, Gagnon-Sanschagrin, and Wu are employees of Analysis Group, which received consultancy fees from Ferring Pharmaceuticals for work on this study. Jhaveri is a full-time employee of Ferring Pharmaceuticals. Parts of this work were presented as a poster presentation at AMCP Nexus 2018; October 22-25, 2018; Orlando, FL.

Introduction: Agitation in individuals with Alzheimer's disease (AD) may predict institutionalization. This study assessed the incremental risk and costs associated with agitation in individuals with AD., Methods: A retrospective analysis of the National Alzheimer's Coordinating Center Uniform Data Set (June 2005-February 2018) was conducted. Incremental risk of institutionalization associated with agitation was estimated and used with the number of institutionalized individuals with AD and agitation and costs of living by residential setting in the United States (literature-based), to estimate incremental institutionalization costs., Results: The analysis included 11,348 individuals with AD: 6603 (58.2%) with and 4745 (41.8%) without agitation. Compared with individuals without agitation, those with agitation were 20% more likely to be institutionalized (odds ratio = 1.20; 95% CI = 1.08-1.33). Total incremental cost of institutionalization associated with agitation was $4.3 billion ($50,588/individual)., Discussion: Agitation is associated with a higher risk of institutionalization among patients with AD, which translates into a substantial economic burden., (© 2019 The Authors.)

Objective: This retrospective observational study assessed if second-line chemotherapy vs. androgen receptor-targeted agents (ARTAs; abiraterone/enzalutamide) is associated with improved outcomes in metastatic castration-resistant prostate cancer (mCRCaP) patients who experience early progression on first-line ARTAs in a US community setting., Methods: Patients with mCRCaP (n = 345) who progressed ≤ 12 months after first-line ARTA and received second-line chemotherapy (docetaxel/cabazitaxel; n = 147) or ARTA (n = 198) between May 2011 and October 2014 were identified. Overall survival (OS), prostate-specific antigen (PSA) response and progression, and clinical response were compared for second-line chemotherapy vs. ARTA, using one-sided tests from second-line therapy initiation. Multivariate analyses were adjusted for: year, age, metastases, opioid use, Eastern Cooperative Oncology Group performance score, PSA, hemoglobin, alkaline phosphatase, lactate dehydrogenase (LDH), and albumin levels., Results: Patients receiving second-line chemotherapy vs. ARTA were younger (median: 74 vs. 79 years) and had a poorer prognosis in terms of PSA, LDH, alkaline phosphatase, albumin and hemoglobin levels, opioid use, and Halabi risk score (P < 0.05). Response rates were higher for chemotherapy vs. ARTA (PSA: adjusted odds ratio = 2.27, P = 0.005; clinical: adjusted odds ratio = 1.78; P = 0.020) and time to PSA progression was longer (adjusted hazard ratio [aHR] = 0.66; P = 0.010). A trend favored chemotherapy vs. ARTA for OS (aHR = 0.81, P = 0.148). Among patients with poor prognostic features, those receiving chemotherapy had significantly improved OS (Halabi intermediate-/high-risk score: aHR = 0.55, P = 0.009; hemoglobin < 11 g/dl: aHR = 0.41, P = 0.002; LDH > upper limit of normal: aHR = 0.18, P = 0.014; albumin < lower limit of normal: aHR = 0.42, P = 0.020)., Conclusion: Following early progression on first-line ARTA, second-line chemotherapy may be more beneficial in mCRCaP compared with second-line ARTA in patients with a poor prognosis., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the real-world risk of developing adverse medical conditions (AMCs) among patients with psoriasis treated with biologic therapies or conventional systemic/topical therapies (CST/topical). Methods: Adult patients with psoriasis were identified from the Truven MarketScan US claims database (2008 Q3–2015 Q3) and classified into cohorts based on treatment initiated on the index date (adalimumab [ADA], etanercept [ETN], ustekinumab [UST], infliximab [IFX], or CST/topical). Incident AMCs were identified while on treatment from diagnoses recorded in medical claims and included abnormal test results, infections, mental disorders, cardiovascular disease, malignancies (skin and non-skin), and respiratory disease. Cox proportional hazards models were used to compare AMC risk for (1) ADA, ETN, and UST (separately) vs CST/topical, and (2) ADA vs other biologic therapies (ETN, UST, and IFX combined). Regressions were adjusted for age, gender, region, insurance plan type, year, Charlson comorbidity index, and prior AMCs; and based on stepwise selection, comorbidities, specialist encounters, and frequently prescribed treatments. Results: A total of 42,981 patients were identified (ADA: 5,197; ETN: 3,311; UST: 1,370; IFX: 187; CST/topical: 32,916). Across cohorts, median age was 46–50 years, 46.2%–53.1% were female, and median follow-up duration was 3.3–7.9 months. For all cohorts, infection was the most frequent AMC (28.7%–41.8%). Compared with CST/topical, ADA, ETN, and UST were associated with a lower risk of infections (adjusted hazard ratio [aHR]: 0.93, 0.92, and 0.86, respectively, all P<0.05). ADA was associated with a lower risk of malignancies (aHR: 0.71, P<0.05), and ETN was associated with a lower risk of respiratory disease (aHR: 0.80, P<0.05). Compared with biologic therapies, ADA was not associated with higher risk of AMCs. Conclusions: Compared to CST/topical, biologic therapies were associated with similar or lower risk of AMCs. Comparison between ADA and other biologic therapies suggests a similar safety profile with respect to the studied AMCs.

Background: There exist several predictive risk models for cardiovascular disease (CVD), including some developed specifically for patients with type 2 diabetes mellitus (T2DM). However, the models developed for a diabetic population are based on information derived from medical records or laboratory results, which are not typically available to entities like payers or quality of care organizations. The objective of this study is to develop and validate models predicting the risk of cardiovascular events in patients with T2DM based on medical insurance claims data., Methods: Patients with T2DM aged 50 years or older were identified from the Optum™ Integrated Real World Evidence Electronic Health Records and Claims de-identified database (10/01/2006-09/30/2016). Risk factors were assessed over a 12-month baseline period and cardiovascular events were monitored from the end of the baseline period until end of data availability, continuous enrollment, or death. Risk models were developed using logistic regressions separately for patients with and without prior CVD, and for each outcome: (1) major adverse cardiovascular events (MACE; i.e., non-fatal myocardial infarction, non-fatal stroke, CVD-related death); (2) any MACE, hospitalization for unstable angina, or hospitalization for congestive heart failure; (3) CVD-related death. Models were developed and validated on 70% and 30% of the sample, respectively. Model performance was assessed using C-statistics., Results: A total of 181,619 patients were identified, including 136,544 (75.2%) without prior CVD and 45,075 (24.8%) with a history of CVD. Age, diabetes-related hospitalizations, prior CVD diagnoses and chronic pulmonary disease were the most important predictors across all models. C-statistics ranged from 0.70 to 0.81, indicating that the models performed well. The additional inclusion of risk factors derived from pharmacy claims (e.g., use of antihypertensive, and use of antihyperglycemic) or from medical records and laboratory measures (e.g., hemoglobin A1c, urine albumin to creatinine ratio) only marginally improved the performance of the models., Conclusion: The claims-based models developed could reliably predict the risk of cardiovascular events in T2DM patients, without requiring pharmacy claims or laboratory measures. These models could be relevant for providers and payers and help implement approaches to prevent cardiovascular events in high-risk diabetic patients.

Background: Psoriasis is a risk factor for cardiovascular events., Objective: To assess the risk of major cardiovascular events and the effect of cumulative treatment exposure on cardiovascular event risk in patients with psoriasis treated with tumor necrosis factor-α inhibitors (TNFis) versus phototherapy., Methods: Adult patients with psoriasis were selected from a large US administrative claims database (from the first quarter of 2000 through the third quarter of 2014) and classified in 2 mutually exclusive cohorts based on whether they were treated with TNFis or phototherapy. Cardiovascular event risk was compared between cohorts using multivariate Cox proportional hazards models. Cumulative exposure was defined based on treatment persistence., Results: A total of 11,410 TNFi and 12,433 phototherapy patients (psoralen plus ultraviolet A light phototherapy, n = 1117; ultraviolet B light phototherapy, n = 11,316) were included in this study. TNFi patients had a lower risk of cardiovascular events compared to phototherapy patients (adjusted hazard ratio 0.77, P < .05). The risk reduction associated with 6 months of cumulative exposure was 11.2% larger for patients treated with TNFis compared to phototherapy (P < .05)., Limitations: Information on psoriasis severity and mortality was limited/not available., Conclusions: Patients with psoriasis who were treated with TNFis exhibited a lower cardiovascular event risk than patients treated with phototherapy. Cumulative exposure to TNFis was associated with an incremental cardiovascular risk reduction compared to phototherapy., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

This study describes short-term and long-term healthcare resource utilization (HRU) and costs following an allogeneic hematopoietic stem cell transplant (HSCT) in adult patients with diffuse large B-cell lymphoma (DLBCL) in a real-world setting. Among 101 patients with DLBCL receiving an allogeneic HSCT, HRU and direct healthcare costs for up to three years after the allogeneic HSCT are described. HRU and costs were substantial, with the most intensive HRU and highest healthcare costs observed during the first year after HSCT (38 inpatient days; 68 days with office visits and average healthcare costs of $455,741). Although HRU and costs decreased over time, they remained high even in the third year after HSCT (four inpatient days; 27 days with office visits and average healthcare costs of $72,957). Overall, this study showed that the economic burden following an allogeneic HSCT in DLBCL patients is significant.

Adverse event (AE)-related costs represent an important component of economic models for cancer care. However, since previous studies mostly focused on specific AEs, treatments, or cancer types, limited information is currently available. Therefore, this study assessed the incremental healthcare costs associated with a large number of AEs among patients diagnosed with some of the most prevalent types of cancer. Data were obtained from a large US claims database. Adult patients were included if diagnosed with and treated for one of the following cancer types: breast, digestive organs and peritoneum, genitourinary organs (including bladder and ovary and other uterine adnexa), lung, lymphatic and hematopoietic tissue, and skin. Treatment episodes were defined as the period from initiation of the first antineoplastic pharmacologic therapy to discontinuation (i.e., gap of ≥ 45 days), or change in treatment regimen, or end of data availability. A total of 36 AEs were selected from the product inserts of 104 treatments recommended by practice guidelines. A retrospective matched cohort design was used, matching a treatment episode with a certain AE with a treatment episode without that AE. A total of 412,005 patients were selected, for a total of 794,243 treatment episodes, resulting in 1,617,368 matched treatment episodes across all 36 AEs. Incremental healthcare costs associated with AEs of any severity ranged from $546 for cough/upper respiratory infections to $24,633 for gastrointestinal perforation. The three most costly AEs when considering any severity were gastrointestinal perforation ($24,633), central nervous system hemorrhage ($24,322), and sepsis/septicemia ($23,510). Incremental healthcare costs associated with severe AEs ranged from $15,709 for dermatitis and rash to $48,538 for gastrointestinal fistula. The three most costly severe AEs were gastrointestinal fistula ($48,538), gastrointestinal perforation ($41,281), and central nervous system hemorrhage ($38,428). In conclusion, AEs during treatment episodes for cancer were frequent and associated with a substantial economic burden.

Background: Psoriasis (Ps) is a chronic inflammatory immune-mediated skin disease that has been identified as a risk factor for various conditions including neoplasms., Objective: To compare prevalence of cancer between Ps and Ps-free patients., Methods: Adult patients continuously enrolled for ≥12 months (≥1 month in 2014) were selected from a large United States (US) claims database (Q1:2010-Q4:2014) and classified as Ps patients (≥2 Ps diagnoses; International Classification of Diseases 9th Revision, [ICD-9] code: 696.1x) and Ps-free patients (no Ps diagnosis). Patients were exactly matched (1:1) based on age, gender, state of residence, and insurance plan type. Prevalence of cancer was compared between cohorts over patients' last 12 months of continuous healthcare plan enrollment using logistic-regression models., Results: A total of 179,066 pairs of Ps and Ps-free patients were selected. Median age was 54.0 years, 51.7% were females. Prevalence of cancer was higher among Ps patients for any type of neoplasms (OR [95% confidence interval (CI)]=1.86 [1.83; 1.89]), malignant neoplasms (OR [95% CI]=1.53 [1.49;1.57]), as well as malignant skin neoplasms (OR [95% CI]=1.87 [1.79; 1.95]), lymphatic and hematopoietic tissues (OR [95% CI]=1.70 [1.57;1.84]), genital (OR [95% CI]=1.33 [1.26;1.41]), breast (OR [95% CI]=1.32 [1.24;1.40]), digestive organs and peritoneum (OR [95% CI]=1.24 [1.13;1.35]), urinary organs (OR [95% CI]=1.49 [1.36;1.64]), respiratory and intrathoracic organs (OR [95% CI]=1.30 [1.17;1.44]), and metastatic cancer (OR [95% CI]=1.14 [1.06;1.24]), all P less than 0.01., Limitations: Impact of Ps severity could not be assessed., Conclusion: Ps patients had a higher prevalence of cancer than Ps-free patients. J Drugs Dermatol. 2018;17(2):180-186.

Objectives: To develop and validate a predictive model for first severe chronic obstructive pulmonary disease (COPD) exacerbation using health insurance claims data and to validate the risk measure of controller medication to total COPD treatment (controller and rescue) ratio (CTR)., Study Design: A predictive model was developed and validated in 2 managed care databases: Truven Health MarketScan database and Reliant Medical Group database. This secondary analysis assessed risk factors, including CTR, during the baseline period (Year 1) to predict risk of severe exacerbation in the at-risk period (Year 2)., Methods: Patients with COPD who were 40 years or older and who had at least 1 COPD medication dispensed during the year following COPD diagnosis were included. Subjects with severe exacerbations in the baseline year were excluded. Risk factors in the baseline period were included as potential predictors in multivariate analysis. Performance was evaluated using C-statistics., Results: The analysis included 223,824 patients. The greatest risk factors for first severe exacerbation were advanced age, chronic oxygen therapy usage, COPD diagnosis type, dispensing of 4 or more canisters of rescue medication, and having 2 or more moderate exacerbations. A CTR of 0.3 or greater was associated with a 14% lower risk of severe exacerbation. The model performed well with C-statistics, ranging from 0.711 to 0.714., Conclusions: This claims-based risk model can predict the likelihood of first severe COPD exacerbation. The CTR could also potentially be used to target populations at greatest risk for severe exacerbations. This could be relevant for providers and payers in approaches to prevent severe exacerbations and reduce costs.

Importance: While psoriasis (Ps) is mainly characterized as an adult disease, it can also develop during childhood. However, prevalence estimates of pediatric psoriasis in the United States (US) are lacking., Objective: To assess the 2015 annual prevalence of Ps and moderate-to-severe Ps in pediatric individuals in the US., Design: This is a retrospective study based on a large administrative insurance claims database in the US., Setting: Data were extracted from the Truven Health Analytics MarketScan® Commercial Claims and Encounters database, which covers over 60 million individuals with employer-provided health insurance across the US., Participants: Over 4.3 million of individuals continuously enrolled in their healthcare plan in 2015 and under 18 years of age were included in the study. Intervention(s) for Clinical Trials or Exposure(s) for Observational Studies: Not applicable. Main Outcome(s) and Measure(s): Ps was defined based on medical claims with a diagnosis of Ps (ICD-9-CM: 696.1); moderate-to-severe Ps was defined based on medical or pharmacy claims for a systemic treatment (biologic, conventional systemic, or phototherapy) for Ps. Overall and age- and gender-stratified prevalence was estimated for both Ps and moderate-to-severe Ps., Results: The prevalence of Ps was estimated at 128 cases per 100,000 individuals (95% CI: 124-131), that of moderate-to-severe Ps at 16 cases per 100,000 individuals (95% CI: 15-17) in 2015. For both Ps and moderate-to-severe Ps, prevalence estimates were numerically higher in females than in males (146 per 100,000 vs. 110 per 100,000 and 17 per 100,000 vs. 15 per 100,000) and increased with age, ranging from 30 per 100,000 in the 0-3 year old group to 205 per 100,000 in the 12-17 year old group., Conclusion and Relevance: This study provides robust estimates of the prevalence of pediatric Ps that can inform decisions pertaining to the management of pediatric patients with Ps. J Drugs Dermatol. 2018;17(2):187-194.

It is unclear how treatment sequencing for metastatic castration-resistant prostate cancer (mCRPC) affects real-world patient outcomes. We assessed treatment sequences, patient characteristics and overall survival (OS) in post-docetaxel mCRPC patients. mCRPC patients receiving second-line cabazitaxel or androgen receptor-targeted therapy (ART; abiraterone/enzalutamide) post-docetaxel were identified using electronic medical records. OS was assessed from second-line therapy initiation using Cox regressions adjusting for: metastases; prostate-specific antigen (PSA); hemoglobin; alkaline phosphatase (ALP); albumin; second-line therapy initiation year. Following docetaxel (n = 629), 123 (19.6%) and 506 (80.4%) patients received cabazitaxel and ART, respectively. One hundred and ninety-five patients received additional treatments thereafter (54 following cabazitaxel; 141 following ART). Although patients receiving second-line cabazitaxel versus ART had similar disease characteristics at first-line therapy initiation, at second-line therapy initiation they had higher mean PSA (386.6 vs. 233.9 ng/mL) and ALP (182.0 vs. 167.3 u/L), lower mean hemoglobin (10.8 vs. 11.5 g/dL), and more frequently had intermediate/high-risk Halabi scores (61.8 vs. 48.4%); all p < 0.05. Overall, crude survival was not significantly different. Among Halabi high-risk patients, adjusted median OS was significantly longer in patients receiving cabazitaxel versus ART (HR 0.48; 95% CI 0.24-0.93; p = 0.030). Low albumin and hemoglobin led to similar findings (HR 0.43; 95% CI 0.23-0.80; p = 0.0077; HR 0.60; 95% CI 0.40-0.90; p = 0.014). Most post-docetaxel patients received second-line ART. Patients receiving second-line cabazitaxel had more high-risk features; however, second-line cabazitaxel administered after docetaxel may improve OS in patients with Halabi high-risk scores or low albumin/hemoglobin.

Background: In metastatic castration-resistant prostate cancer (mCRPC), optimal treatment sequences are unknown. We assessed second-line taxane (TT) versus androgen receptor-targeted therapy (ART), after initial ART failure, in United States oncology community practices., Patients and Methods: Using electronic medical records, patients with mCRPC receiving first-line ART and second-line therapy (TT, ART) were identified. Response and overall survival (OS) were evaluated from second-line therapy initiation. Multivariate analyses were adjusted for year, age, metastases, opioid use, prostate-specific antigen (PSA), hemoglobin, alkaline phosphatase, and albumin levels., Results: Of 546 patients receiving first-line ART, 206 and 340 received second-line TT and ART. Compared with patients receiving second-line ART, patients receiving TT were younger (median, 74 vs. 79 years), more had intermediate-high Halabi risk scores (59% vs. 35%), had higher opioid use (42% vs. 22%), median PSA (116 vs. 48 ng/mL), alkaline phosphatase (112 vs. 87 U/L), and lactate dehydrogenase (254 vs. 201 U/L), and had lower hemoglobin (11.2 vs. 12.3 g/dL) and albumin levels (3.8 vs. 4.0 g/dL); all P < .001. Response rates were higher with second-line TT versus ART (clinical response, 44.2% vs. 24.7%; P = .006; PSA response, 44.5% vs. 28.7%; P = .004). OS did not differ between cohorts (hazard ratio [HR], 0.90; P = .511). Among patients with a poor prognosis (hemoglobin < 11 g/d; albumin < lower limit of normal), those receiving second-line TT versus ART showed improved OS (HR, 0.52; P = .004 and HR, 0.36; P = .003, respectively)., Conclusions: Despite more severe disease profiles, patients with mCRPC receiving second-line TT versus ART achieved higher response rates after initial ART. Poor prognosis patients had improved OS with second-line TT versus ART., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rationale: Current chronic obstructive pulmonary disease (COPD) exacerbation risk prediction models are based on clinical data not easily accessible to national quality-of-care organizations and payers. Models developed from data sources available to these organizations are needed., Objectives: This study aimed to validate a risk measure constructed using pharmacy claims in patients with COPD. Administrative claims data were used to construct a risk model to test and validate the ratio of controller (maintenance) medications to total COPD medications (CTR) as an independent risk measure for COPD exacerbations. The ability of the CTR to predict the risk of COPD exacerbations was also assessed., Methods: This was a retrospective study using health insurance claims data from the Truven MarketScan database (2006-2011), whereby exacerbation risk factors of patients with COPD were observed over a 12-month period and exacerbations monitored in the following year. Exacerbations were defined as moderate (emergency department or outpatient treatment with oral corticosteroid dispensings within 7 d) or severe (hospital admission) on the basis of diagnosis codes. Models were developed and validated using split-sample data from the MarketScan database and further validated using the Reliant Medical Group database. The performance of prediction models was evaluated using C-statistics., Measurements and Main Results: A total of 258,668 patients with COPD from the MarketScan database were included. A CTR of greater than or equal to 0.3 was significantly associated with a reduced risk for any (adjusted odds ratio [OR], 0.91; 95% confidence interval [CI], 0.85-0.97); moderate (OR, 0.93; 95% CI, 0.87-1.00), or severe (OR, 0.87; 95% CI, 0.80-0.95) exacerbation. The CTR, at a ratio of greater than or equal to 0.3, was predictive in various subpopulations, including those without a history of asthma and those with or without a history of moderate/severe exacerbations. The C-statistics ranged from 0.750 to 0.761 for the development set and 0.714 to 0.761 in the validation sets, indicating the CTR performed well in predicting exacerbation risk., Conclusions: The ratio of controller to total medications dispensed for COPD is a measure that can easily be calculated using only pharmacy claims data. A CTR of greater than or equal to 0.3 can potentially be used as a quality-of-care measurement for prevention of exacerbations.

Trastuzumab reduces the risk of relapse in women with HER2-positive non-metastatic breast cancer, but little information exists on the timing of trastuzumab initiation. The study investigated the impact of delaying the initiation of adjuvant trastuzumab therapy for >6 months after the breast cancer diagnosis on time to relapse, overall survival (OS), and relapse-free survival (RFS) among patients with non-metastatic breast cancer. Adult women with non-metastatic breast cancer who initiated trastuzumab adjuvant therapy without receiving any neoadjuvant therapy were selected from the US Department of Defense health claims database from 01/2003 to 12/2012. Two study cohorts were defined based on the time from breast cancer diagnosis to trastuzumab initiation: >6 months and ≤6 months. The impact of delaying trastuzumab initiation on time to relapse, OS, and RFS was estimated using Cox regression models adjusted for potential confounders. Of 2749 women in the study sample, 79.9 % initiated adjuvant trastuzumab within ≤6 months of diagnosis and 20.1 % initiated adjuvant trastuzumab >6 months after diagnosis. After adjusting for confounders, patients who initiated trastuzumab >6 months after the breast cancer diagnosis had a higher risk of relapse, death, or relapse/death than those who initiated trastuzumab within ≤6 months of diagnosis (hazard ratios [95 % CIs]: 1.51 [1.22-1.87], 1.54 [1.12-2.12], and 1.43 [1.16-1.75]; respectively). The results of this population-based study suggest that delays of >6 months in the initiation of trastuzumab among HER2-positive non-metastatic breast cancer patients are associated with a higher risk of relapse and shorter OS and RFS.

Purpose: The NSABP Trial B-31 and NCCTG Trial N9831 (B-31/N9831 trials, Romond et al. in N Engl J Med 353:1673-84, 2005. doi:10.1056/NEJMoa052122; Perez et al. in J Clin Oncol 32:3744-52, 2014. doi:10.1200/JCO.2014.55.5730) established the efficacy of adjuvant trastuzumab for patients with HER2-positive early stage breast cancer. We aimed to estimate the overall survival (OS) and relapse-free survival (RFS) of HER2-positive non-metastatic breast cancer patients treated with adjuvant trastuzumab in a clinical practice setting in the United States., Methods: Adult women initiating adjuvant trastuzumab within 1 year of breast cancer surgery were identified in the health claims database of the US Department of Defense (01/2003-12/2012). OS and RFS unadjusted rates at 4 and 6 years after the first trastuzumab treatment following the breast cancer diagnosis were estimated from Kaplan-Meier analyses., Results: The study sample included 3188 women followed for a median of 3.3 years after trastuzumab initiation and treated continuously with trastuzumab for a median of 12 months. The OS rates (95 % confidence intervals) at 4 and 6 years were 90.0 % (88.6-91.2) and 87.1 (85.3-88.6), respectively. The corresponding RFS rates were 75.8 % (74.0-77.5) and 72.7 (70.7-74.7), respectively. The OS and RFS rates at 6 years reported in the B-31/N9831 trials were 89.8 and 81.4 %, respectively., Conclusions: OS rates estimated in this study were in range with those estimated in the B-31/N9831 trials, while RFS rates were lower. However, patients in the B-31/N9831 trials were younger and possibly had fewer comorbidities than patients in the current study; these differences were not adjusted for in the crude OS and RFS analyses.

This study evaluated the incremental healthcare costs associated with Fragile X syndrome (FXS) for patients and their caregivers. Using administrative healthcare claims data (1999-2012), subjects with ≥ 1 FXS diagnosis (ICD-9-CM: 759.83) were matched 1:5 with non-FXS controls using high-dimensional propensity scores. Costs and resource utilization were examined. Among employees, payment for disability leave and absenteeism were also examined. We identified 590 FXS and 2,950 non-FXS individuals along with 647 and 2,611 caregivers, respectively. FXS patients and their caregivers experienced higher all-cause direct costs compared to control cohorts (total[SD]: $14,677[46,752] vs. $6,103[26,081]; $5,259[19,360] vs. $2,120[6,425], respectively, p < 0.05). Employed FXS patients and caregivers had higher indirect costs compared to their controls (total[SD]: $4,477[5,161] vs. $1,751[2,556]; $2,641[4,238] vs. $1,211[1,936], respectively, p < 0.05).