Evaluation of inpatient and emergency department healthcare resource utilization and costs pre- and post-nusinersen for the treatment of spinal muscular atrophy using United States claims.

Aim: Nusinersen, administered by intrathecal injection at a dose of 12 mg, is indicated across all ages for the treatment of spinal muscular atrophy (SMA). Evidence on real-world healthcare resource use (HRU) and costs among patients taking nusinersen remains limited. This study aimed to evaluate real-world HRU and costs associated with nusinersen use through US claims databases. Patients & methods: Using the Merative™ MarketScan® Research Databases, patients with SMA receiving nusinersen were identified from commercial (January 2017 to June 2020) and Medicaid claims (January 2017 to December 2019). Those likely to have complete information on the date of nusinersen initiation and continuous enrollment 12 months pre- and post-index (first record of nusinersen treatment) were retained. Number and costs (US$ 2020) of inpatient admissions and emergency department (ED) visits, unrelated to nusinersen administration, were evaluated for 12 months pre- and post-nusinersen initiation and stratified by age: pediatric (<18 years) and adult (≥18 years). Results: Overall, 103 individuals treated with nusinersen were retained: 59 were pediatric (mean age [range]: 9 [1-17] years), and 44 were adults (30 [18-63] years). Inpatient admissions decreased by 41% for pediatrics and 67% for adults in the 12 months post-treatment versus the 12 months pre-treatment. Average inpatient admission costs per patient for the pediatric cohort decreased by 63% ($22,903 vs $8466) and by 79% ($13,997 vs $2899) for the adult cohort when comparing the 12 months pre-index with the 12 months post-index period. Total ED visits and ED visit costs decreased by 8% and 35%, respectively, for the overall cohort over the 12-month period pre- and post-index. Conclusion: Using US claims databases, nusinersen treatment in pediatric and adult patients was associated with reductions in HRU and costs over a 12-month period post-treatment initiation relative to the pre-treatment period.

Confounder Adjustment Using the Disease Risk Score: A Proposal for Weighting Methods.

Propensity score analysis is a common approach to addressing confounding in nonrandomized studies. Its implementation, however, requires important assumptions (e.g., positivity). The disease risk score (DRS) is an alternative confounding score that can relax some of these assumptions. Like the propensity score, the DRS summarizes multiple confounders into a single score, on which conditioning by matching allows the estimation of causal effects. However, matching relies on arbitrary choices for pruning out data (e.g., matching ratio, algorithm, and caliper width) and may be computationally demanding. Alternatively, weighting methods, common in propensity score analysis, are easy to implement and may entail fewer choices, yet none have been developed for the DRS. Here we present 2 weighting approaches: One derives directly from inverse probability weighting; the other, named target distribution weighting, relates to importance sampling. We empirically show that inverse probability weighting and target distribution weighting display performance comparable to matching techniques in terms of bias but outperform them in terms of efficiency (mean squared error) and computational speed (up to >870 times faster in an illustrative study). We illustrate implementation of the methods in 2 case studies where we investigate placebo treatments for multiple sclerosis and administration of aspirin in stroke patients.

A Critical Appraisal of Matching-Adjusted Indirect Comparisons in Spinal Muscular Atrophy.

In the absence of head-to-head trials, indirect treatment comparisons (ITCs) are often used to compare the efficacy of different therapies to support decision-making. Matching-adjusted indirect comparison (MAIC), a type of ITC, is increasingly used to compare treatment efficacy when individual patient data are available from one trial and only aggregate data are available from the other trial. This paper examines the conduct and reporting of MAICs to compare treatments for spinal muscular atrophy (SMA), a rare neuromuscular disease. A literature search identified three studies comparing approved treatments for SMA including nusinersen, risdiplam, and onasemnogene abeparvovec. The quality of the MAICs was assessed on the basis of the following principles consolidated from published MAIC best practices: (1) justification for the use of MAIC is clearly stated, (2) the included trials with respect to study population and design are comparable, (3) all known confounders and effect modifiers are identified a priori and accounted for in the analysis, (4) outcomes should be similar in definition and assessment, (5) baseline characteristics are reported before and after adjustment, along with weights, and (6) key details of a MAIC are reported. In the three MAIC publications in SMA to date, the quality of analysis and reporting varied greatly. Various sources of bias in the MAICs were identified, including lack of control for key confounders and effect modifiers, inconsistency in outcome definitions across trials, imbalances in important baseline characteristics after weighting, and lack of reporting key elements. These findings highlight the importance of evaluating MAICs according to best practices when assessing the conduct and reporting of MAICs.

Examining Real-World Adherence to Nusinersen for the Treatment of Spinal Muscular Atrophy Using Two Large US Data Sources.

INTRODUCTION: Spinal muscular atrophy (SMA) is a rare neuromuscular disease characterized by progressive muscular atrophy and weakness. Nusinersen was the first treatment approved for SMA. Per the US label, the nusinersen administration schedule consists of three loading doses at 14-day intervals, a fourth loading dose 30 days later, and maintenance doses every 4 months thereafter. Using two large US databases, we evaluated real-world adherence to nusinersen with its unique dosing schedule among generalizable populations of patients with SMA. METHODS: Patients with SMA treated with nusinersen, likely to have complete information on date of treatment initiation, were identified in the Optum® de-identified electronic health records (EHR) database (7/2017-9/2019), and in the Merative™ MarketScan® Research Databases from commercial (1/2017-6/2020) and Medicaid claims (1/2017-12/2019). Baseline demographics, number of nusinersen administrations on time, and distribution of inter-dose intervals were summarized. RESULTS: Totals of 67 and 291 patients were identified in the EHR and claims databases, respectively. Most nusinersen doses were received on time (93.9% EHR, 80.5% claims). Adherence was higher during the maintenance phase (90.6%) than the loading phase (71.1%) in the claims analysis, in contrast with the EHR analysis (95.5% and 92.6%, respectively), suggesting that not all loading doses of nusinersen may be accurately captured in claims. Inter-dose intervals captured in both databases aligned with the expected dosing schedule. CONCLUSION: Most nusinersen doses were received on time, consistent with the recommended schedule. Our findings also highlight the importance of careful methodological approaches when using real-world administrative databases for evaluation of nusinersen treatment patterns.

Adherence to medicines in the real world is important for patients with chronic disease to see long-term benefits of treatment. This study shows the importance and challenges of measuring adherence using real-world administrative data sources. This is especially important for drugs given through lumbar puncture with unique dosing schedules, such as nusinersen for the treatment of spinal muscular atrophy. In this study, most patients with spinal muscular atrophy received their nusinersen doses on time.

Real-world Adherence to Nusinersen in Adults with Spinal Muscular Atrophy in the US: A Multi-site Chart Review Study.

Limited evidence exists on real-world adherence to nusinersen for the treatment of spinal muscular atrophy (SMA). Data are presented from a multi-site retrospective chart review of 86 adults with SMA initiating nusinersen at nine US centers between January 2017 and February 2019. Seventy-nine (92%) adults remained on nusinersen during the study; 454 (92%) of 493 total nusinersen doses were received on time. Fifty-eight (67%) adults received all nusinersen doses on time. The majority of patients with at least one nonadherent dose resumed nusinersen on time. Most patients followed the dosing schedule across the loading and maintenance dose periods.

Use of Antiretroviral Therapy for a US Medicaid Enrolled Pediatric Cohort with HIV.

Appropriate antiretroviral therapy use in children with Human Immunodeficiency Virus (HIV) is essential for optimizing clinical outcomes and preventing HIV transmission. To describe and determine correlates of HIV antiretroviral therapy (ART) persistence and implementation for children and adolescents in the United States. We studied Medicaid enrollees (ages 2-19 years) with HIV in 14 states in 2011 and 2012. We defined non-persistence as a discontinuation of an ART regimen for at least 90 days, and calculated implementation as the proportion of days on ART while persistent. We used Cox proportional regression and logistic regression to determine characteristics associated with ART non-persistence and poor (< 90%) implementation, respectively. Among those with ≥ 1 year of observation (n = 8679), 55.7% never received ART. For ART recipients (n = 3849), 34.9% discontinued ART. Correlates of ART non-persistence included older age (e.g., 15-19 vs. 2-5 years [adjusted hazard ratio (aHR) 2.9, 95% CI 2.1-4.0]; females vs. males (aHR 1.2; 1.1-1.3); mental health conditions (aHR 1.3; 1.1-1.5), drug/alcohol abuse (aHR 1.2; 1.0-1.5) and HIV-related conditions (aHR 1.2; 1.0-1.4). Those with an outpatient visit were less likely to discontinue an ART (aHR 0.32; 0.28-0.36). During persistent episodes, 42.3% had poor ART implementation. Correlates of poor implementation included females vs. males (aOR 1.2; 95% CI 1.0-1.3), Black vs. White race (aOR 1.3; 95% CI 1.1-1.7) and Hispanic/Latino vs. White (aOR 1.3; 1.0-1.8). Among Medicaid youth with HIV, there were low rates of ART exposure, and ART discontinuation was common. Correlates of persistence and implementation differed, suggesting a need for varying clinical interventions to improve connection to care and ensuring ongoing engagement with ART use.

Population-level changes in outcomes and Medicare cost following the introduction of new cancer therapies.

OBJECTIVE: To examine the population-level impacts of the introduction of novel cancer therapies with high cost in the United States, using immunotherapies in advanced nonsmall cell lung cancer (NSCLC) as an example. DATA SOURCES: Surveillance, Epidemiology, and End Results data in 2012-2015 linked to Medicare fee-for-service claims until 2016. STUDY DESIGN: We examined population-level trends in treatment patterns, survival, and Medicare spending in patients diagnosed with advanced NSCLC, the leading cause of cancer death in the United States, between 2012 and 2015. We estimated the percentage of patients who received any antineoplastic therapy within two years of diagnosis, including novel immunotherapies. We compared the trends in overall survival and mean two-year Medicare spending per each patient before and after the introduction of immunotherapies in 2015. DATA COLLECTION/EXTRACTION METHODS: Not Applicable. PRINCIPAL FINDINGS: The percentage of patients treated with any antineoplastic therapy remained the same at 46.7% in 2012 and 2015, whereas the use of immunotherapies increased from 0% to 15.2%. The two-year survival rate and median survival increased by 3.3 percentage points (95% CI: 2.0, 4.5) and 0.4 months (CI: 0.0, 0.9), respectively, during the same period. The mean two-year total Medicare spending and outpatient spending per patient increased by $5735 (CI: 3479, 8040) and $7661 (CI: 5902, 9311), respectively, which were largely attributable to the increases in immunotherapy spending by $5806 (CI: 5165, 6459). CONCLUSIONS: The introduction of lung cancer immunotherapies was accompanied by improvements in survival and increases in spending between 2012 and 2015 in the Medicare population. As novel immunotherapies and other target therapies continue to change the clinical management of various cancers, further efforts are needed to ensure their effective and efficient use, and to understand their population-level impacts in the United States.

Real-world use and survival outcomes of immune checkpoint inhibitors in older adults with non-small cell lung cancer.

BACKGROUND: Limited data exist regarding the characteristics and survival outcomes of older adults with non-small cell lung cancer (NSCLC) who receive immune checkpoint inhibitors in routine oncology practice. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified 1256 patients aged ≥65 years who were diagnosed with pathologically confirmed stage I to stage IV NSCLC between 2002 and 2015 and initiated nivolumab or pembrolizumab in 2016. We examined patient characteristics and overall survival from the time of immune checkpoint inhibitor initiation through December 31, 2017. RESULTS: The median patient age at the time of immune checkpoint inhibitor initiatiton was 75.3 years (interquartile range, 8.5). A substantial percentage of patients were initially diagnosed with stage IV disease (42.6%) and had ≥2 comorbid conditions (48.7%). Using a claims-based proxy, 11.5% of patients had poor performance status and 12.6% had a history of autoimmune conditions. The median overall survival after initiation of immune checkpoint inhibitor was 9.3 months (95% CI, 8.5-10.5 months). The 1-year survival rate was 43.0% (95% CI, 40.2-45.7%). In multivariable analyses, multiple comorbid conditions, squamous histology, a history of nonplatinum doublet systemic therapy, recent radiotherapy, and a shorter time from initial diagnosis to treatment initiation were found to be statistically significantly associated with an increased hazard of death. Demographics, poor performance status, and prior autoimmune conditions were not significantly associated with the hazard of death. CONCLUSIONS: Many older adults with NSCLC who initiated immune checkpoint inhibitors had multiple comorbidities, a history of autoimmune disease, or poor performance status. Factors associated with poor prognosis among patients with advanced NSCLC were also associated with worse survival in older adults treated with immune checkpoint inhibitors.

Trends in medication adherence in HIV patients in the US, 2001 to 2012: an observational cohort study.

INTRODUCTION: Adherence to antiretroviral therapy (ART) is essential to reduce HIV-related morbidity and mortality as well as the risk of virological failure and HIV transmission. We determined the trends in ART adherence during the periods of therapeutic advances, wider use of ART and greater attention to ART adherence. To understand the general trends in medication adherence, we compared ART adherence with medications for other common chronic conditions. METHODS: A retrospective cohort study using Medicaid claims between 2001 and 2012 from 14 US states with the highest HIV prevalence. Medicaid is the largest source of care for HIV patients in the US. We identified Medicaid beneficiaries with HIV who initiated ART between 2001 and 2010 (n=23,343). Comparison groups included (1) HIV- persons who initiated a statin, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB), or metformin and (2) HIV+ persons who initiated these control medications while on and not on ART. We estimated adjusted odds of >90% medication implementation during the two years following initiation. RESULTS: The proportion of HIV+ persons with >90% ART implementation increased from 33.5% in those who initiated in 2001 to 46.4% in 2005 and 52.4% in 2010. ART initiators in 2007 to 2010 had 53% increased odds of >90% implementation compared to those in 2001 to 2003 (adjusted OR 1.53, 99% CI: 1.34 to 1.75). Older age, male, White race, newer ART regimens and absence of substance use indicators were also associated with increased odds of >90% ART implementation. No or minimal improvements were found in the implementation of control medications in HIV- persons. For HIV- persons, the adjusted ORs comparing 2007-2010 to 2001-2003 were 1.06, 1.01 and 1.19 for statins, ACEI/ARB, metformin respectively. HIV+ persons who were on ART had, on average, 15.0 (SD: 4.2) and 16.1 (SD: 3.4) percentage points higher >90% implementation rates of concurrent statins, ACEI/ARB or metformin compared to HIV- persons and HIV+ persons who were not on ART respectively. CONCLUSIONS: Adherence to ART substantially improved between 2001 and 2012. Nevertheless, the absolute rates of >90% implementation were low for all groups examined. Substantial disparities by age, sex and race were present, drawing attention to the need to continue to enhance medication adherence. Further studies are required to examine whether these trends and disparities persist in the most recent period.

Ten-year trends in antiretroviral therapy persistence among US Medicaid beneficiaries.

OBJECTIVE: Whether the rate of HIV antiretroviral therapy (ART) persistence has improved over time in the United States is unknown. We examined ART persistence trends between 2001 and 2010, using non-HIV medications as a comparator. METHODS: We conducted a retrospective cohort study using Medicaid claims. We defined persistence as the duration of treatment from the first to the last fill date before a 90-day permissible gap and used Kaplan-Meier curves and Cox proportional hazard models to assess crude and adjusted nonpersistence. The secular trends of ART persistence in 43 598 HIV patients were compared with the secular trends of persistence with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACEI/ARB), statins, and metformin in non-HIV-infected patients and subgroups of HIV patients who started these control medications while using ART. RESULTS: Median time to ART nonpersistence increased from 23.9 months in 2001-2003 to 35.4 months in 2004-2006 and was not reached for those starting ART in 2007-2010. In adjusted models, ART initiators in 2007-2010 had 11% decreased hazard of nonpersistence compared with those who initiated in 2001-2003 (P < 0.001). For non-HIV patients initiating angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB), statins, and metformin, the hazard ratios for nonpersistence comparing 2007-2010 to 2001-2003 were 1.07, 0.94, and 1.02, respectively (all P < 0.001). For HIV patients initiating the three control medications, the hazard ratios of nonpersistence comparing 2007-2010 to 2001-2003 were 0.71, 0.65, and 0.63, respectively (all P < 0.001). CONCLUSION: Persistence with ART improved between 2001 and 2010. Persistence with control medications improved at a higher rate among HIV patients using ART than HIV-negative controls.

Region and Insurance Plan Type Influence Discharge Disposition After Hip and Knee Arthroplasty: Evidence From the Privately Insured US Population.

BACKGROUND: Little is known about regional variation in the use of postacute care services after elective procedures, such as total hip or knee arthroplasty (THA/TKA), and how insurance type may influence it. The goal of this study is to assess the influence of region and insurance arrangements on discharge disposition. METHODS: A representative sample of the privately insured US population with THA or TKA in 2009 or 2010 was obtained from the MarketScan database applying individual-level weights from the Medical Expenditure Panel Survey. Multivariate logistic regression was used to predict the odds of being discharged to an extended care facility (ECF) compared with being discharged home. The model adjusted for region, insurance plan type, sociodemographic characteristics, comorbidities, and length of stay. RESULTS: Large variability was observed in ECF use across the US. Patients in the Northeast were 2.5 times more likely to receive care at an ECF compared with patients in the South (odds ratio [OR] = 2.51, 95% confidence interval [CI]: 1.97-3.19). Enrollees in noncapitated plans such as fee-for-service plans or exclusive provider organizations were less likely to be discharged to an ECF compared with health maintenance organizations/preferred provider organizations with capitation enrollees (OR = 0.74, 95% CI: 0.57-0.94; OR = 0.49, 95% CI: 0.34-0.74, respectively). CONCLUSION: Region and private insurance plan arrangements are related to extended care use among THA and TKA patients. Understanding regional variation in discharge disposition provides policy makers with important information as to where to focus new tests of hip and knee procedures such as same day arthroplasty.

Patient cost-sharing and insurance arrangements are associated with hospital readmissions after abdominal surgery: Implications for access and quality health care.

BACKGROUND: Readmission rates after operative procedures are used increasingly as a measure of hospital care quality. Patient access to care may influence readmission rates. The objective of this study was to determine the relationship between patient cost-sharing, insurance arrangements, and the risk of postoperative readmissions. METHODS: Using the MarketScan Research Database (n = 121,002), we examined privately insured, nonelderly patients who underwent abdominal surgery in 2010. The main outcome measures were risk-adjusted unplanned readmissions within 7 days and 30 days of discharge. Odds of readmissions were compared with multivariable logistic regression models. RESULTS: In adjusted models, $1,284 increase in patient out-of-pocket payments during index admission (a difference of one standard deviation) was associated with 19% decrease in the odds of 7-day readmission (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.78-0.85) and 17% decrease in the odds of 30-day readmission (OR 0.83, 95% CI 0.81-0.86). Patients in the noncapitated point-of-service plans (OR 1.19, 95% CI 1.07-1.33), preferred provider organization plans (OR 1.11, 95% CI 1.03-1.19), and high-deductible plans (OR 1.12, 95% CI 1.00-1.26) were more likely to be readmitted within 30 days compared with patients in the capitated health maintenance organization and point-of-service plans. CONCLUSION: Among privately insured, nonelderly patients, increased patient cost-sharing was associated with lower odds of 7-day and 30-day readmission after abdominal surgery. Insurance arrangements also were significantly associated with postoperative readmissions. Patient cost sharing and insurance arrangements need consideration in the provision of equitable access for quality care.