Healthcare utilization and direct medical costs of Huntington's disease among Medicaid beneficiaries in the United States.

AIMS: To provide more recent estimates of healthcare utilization and costs in Huntington's disease (HD) in the Medicaid population. MATERIALS AND METHODS: This retrospective analysis used administrative claims data for HD beneficiaries (≥1 HD claim; ICD-9-CM 333.4) from Medicaid Analytic eXtract data files from 1 January 2010-31 December 2014. The date of the first HD claim during the identification period (1 January 2011-31 December 2013) was assigned as the index date. If a beneficiary had multiple HD claims during the identification period, one was randomly chosen as the index date. Beneficiaries were required to be continuously enrolled in fee-for-service plans during the 1-year pre-index and post-index periods. Medicaid beneficiaries without HD were drawn from a 100% random sample and matched (3:1) to those with HD. Beneficiaries were classified by disease stage (early/middle/late). All-cause and HD-related (any utilization related to HD diagnosis or symptoms associated with HD) healthcare utilization and costs were reported. RESULTS: A total of 1,785 beneficiaries without HD were matched to 595 beneficiaries with HD (139 early-, 78 middle-, and 378 late-stage). The mean (SD) annual total costs were higher for beneficiaries with HD than beneficiaries without HD ($73,087 [$75,140] vs. $26,834 [$47,659], p <.001) and driven by inpatient costs ($45,190 [$48,185] vs. $13,808 [$39,596], p <.001). Total healthcare costs were highest among beneficiaries with late-stage HD (mean [SD] cost: $22,797 [$31,683] for early-stage HD vs. $55,294 [$129,290] for middle-stage HD vs. $95,251 [$60,197] for late-stage HD; p <.001). LIMITATIONS: Administrative claims are intended for billing purposes and subject to coding errors. This study did not address functional status, which may provide further insight to late-stage and end-of-life burden of HD, and indirect costs. CONCLUSIONS: Medicaid beneficiaries with HD have higher acute healthcare utilization and costs compared to beneficiaries without HD, which tend to increase with disease progression, indicating that HD beneficiaries at later disease stages have greater burden.

Huntington's disease (HD) is a degenerative genetic disorder marked by progressive decline in cognitive and motor functions, leading to severe disability and loss of independence. The median and mean survival time after a diagnosis of HD is 15 years. Little is known about the kinds of health services used or costs associated with HD in the United States (US) in the Medicaid population. The study objective was to estimate healthcare utilization and direct medical spending among Medicaid beneficiaries with HD. The mean annual total costs were higher for beneficiaries with HD than beneficiaries without HD ($73,087 vs. $26,834). Mean total healthcare costs were highest among beneficiaries with late-stage HD ($22,797 for early-stage HD vs. $55,294 for middle-stage HD vs. $95,251 for late-stage HD). Medicaid beneficiaries with HD have higher acute healthcare utilization and costs compared to beneficiaries without HD, with utilization and costs increasing with disease progression, indicating that HD beneficiaries at later disease stages have greater burden.

Healthcare resource utilization and cost among individuals with late-onset versus adult-onset Huntington's disease: a claims­based retrospective cohort study.

AIMS: Quantify healthcare resource utilization (HRU) and costs for individuals with late-onset Huntington's disease (LoHD) and compare these with adult-onset HD (AoHD) and non-HD controls. METHODS: This retrospective cohort study used US healthcare claims data from the IBM MarketScan Commercial and Medicare Supplemental Databases. Individuals newly diagnosed with HD between 1/1/2009 and 12/31/2017 were selected (index date was first HD claim). Individuals ≥60 years of age at the index date were categorized as having LoHD while individuals 21-59 years of age were categorized as having AoHD. Non­HD controls were exact matched 2:1 to LoHD and AoHD cohorts. Individuals were required to have continuous enrollment for ≥12 months pre- and post-index. Twelve-month all-cause HRU and healthcare costs were assessed for each cohort. RESULTS: In total, 763 individuals with LoHD and 1,073 individuals with AoHD were matched with 3,762 non-HD controls. Unadjusted all-cause HRU in the 12 months post-index was higher for individuals with LoHD and AoHD compared with non-HD controls across most service categories. Adjusted all-cause HRU for the LoHD cohort was significantly higher compared with non-HD controls across all service categories. In the 12 months post-index, mean total costs for the LoHD cohort ($29,055) were significantly higher than for non-HD controls (≥60 years old: $17,286; 21-59 years old: $12,688; p <.001) and similar to total costs in the AoHD cohort ($31,701; p =.47). LIMITATIONS: It was not possible to control for differences in HD stage but regression models were adjusted for baseline HRU. Evaluations of costs did not include indirect costs, which are known to be significant components of the wider HD burden. CONCLUSIONS: This study provides the first analysis of HRU and costs in LoHD, demonstrating that individuals with LoHD experience a significantly higher healthcare burden compared with non-HD controls and a similarly high burden compared with individuals with AoHD.

Huntington's disease (HD) usually develops between the ages of 30­50 but can develop earlier/later. This study looked at healthcare use in people who developed HD at age 60 or later in the United States. Researchers found that people who develop HD at age 60 or later have similar health needs to people with adult-onset HD. Furthermore, they have much greater health needs than people of a similar age who do not have HD.

Adherence and Persistence to Nusinersen for Spinal Muscular Atrophy: A US Claims-Based Analysis.

INTRODUCTION: Spinal muscular atrophy (SMA) is a genetic, neuromuscular disease caused by deletions and/or mutations in the survival of motor neuron 1 (SMN1) gene leading to reduced SMN protein levels. Nusinersen, an intrathecally administered antisense oligonucleotide therapy that increases SMN protein levels, is approved for use in adult and pediatric patients with SMA. Data to inform real-world patient adherence and persistence to nusinersen are limited, with disparities in the population with SMA, study design, and results. The objective of this study is to characterize real-world nusinersen adherence and persistence in patients with SMA. METHODS: This retrospective study examined nusinersen adherence and persistence over a 2-year period in patients with SMA in the USA from the IQVIA PharMetrics Plus claims database. Patients were followed from the date of first evidence of nusinersen treatment (occurring after 1 July 2017) until the end of the study period (31 December 2019) or end of continuous pharmacy and medical benefit enrollment, whichever came first. Subgroup analyses for nusinersen adherence and persistence were performed on the basis of age and presence or absence of spinal complications. RESULTS: The final cohort consisted of 179 patients with SMA treated with nusinersen. Adherence to nusinersen treatment was 41% at 56 weeks and 39% at 104 weeks. In the base-case persistence analysis, there was a decrease in persistence before 6 months (67%) and further decline at 1 (57%) and 2 years (55%). Patients with spinal complication versus without had numerically higher persistence with nusinersen. CONCLUSIONS: The findings suggest that adherence and persistence to nusinersen treatment appear low. Demographic (age ≥ 18 years) and clinical factors (no spinal complications) may contribute to nusinersen treatment discontinuation. Future research should explore possible reasons for low adherence and persistence to nusinersen treatment, such as clinical or logistical factors, patient preferences, and payer restrictions.

Spinal muscular atrophy (SMA) is a rare, genetic disease that causes patients to lose motor neurons over time. This makes tasks that involve movement control like walking and talking more difficult. SMA can be treated, but it is important that patients receive their scheduled doses of medicine as prescribed and stay on treatment. Nusinersen (SPINRAZA^®) is a treatment for SMA that is given as an intrathecal injection into the cerebrospinal fluid of the spine. Patients receive six doses of nusinersen in the first year. After the first year, patients receive three doses every year for life.This study looked at whether patients received their scheduled doses, also called adherence, and how many patients remained on treatment, or persistence, over two years. This study involved 179 nusinersen-treated patients with SMA and used data from US health insurance plans. After 56 weeks of treatment, 41% of patients were adherent. After 104 weeks, 39% were adherent. After 6 months, 67% of patients were still on treatment. After 1 year, 57% were still on treatment. After 2 years, 55% of patients were still on treatment. The study showed that a low number of patients with SMA, particularly those older than 18 years with no spinal problems, remained on nusinersen for the intended time and received the treatment as prescribed. Future studies will look at possible reasons for low adherence and persistence to nusinersen, which may include difficulties traveling to a clinic or scheduling a visit, patient preference, or insurance restrictions.

Health care resource utilization and costs among individuals with vs without Huntington disease in a US population.

BACKGROUND: Quantifying the extent of health care resource utilization (HCRU) and costs associated with Huntington disease (HD) is vital for providers, decisionmakers, and payers to understand unmet treatment needs and to ensure limited resources can be used to benefit the maximum number of people with HD. OBJECTIVE: To quantify HCRU and costs for people with HD, overall and by disease stage, and compare these with non-HD controls. METHODS: This was a retrospective cohort study using administrative claims data from the IBM MarketScan Commercial, Multi-State Medicaid, and Medicare Supplemental Databases from January 1, 2009, to December 31, 2018. People with an HD claim between January 1, 2010, and December 31, 2017, were selected for this analysis and matched with non-HD controls for comparison. The HD cohort and the non-HD controls were exact matched on their follow-up duration and propensity score matched 1:4 to create the final analytical cohort. Index date was the first HD diagnosis for the HD cohort (proxy index date assigned to controls), and all individuals were required to have continuous enrollment for 12 or more months pre-index (baseline) and 3 or more months post-index. Proportions of all-cause HCRU (ie, outpatient visits, inpatient visits, emergency department visits, pharmacy fills, radiology visits, and physical/occupational therapy visits) in the 6-months post-index and HCRU counts and costs per patient per month (PPPM) over the entire follow-up were calculated for each cohort. RESULTS: A total of 2,473 individuals with HD and 9,522 matched non-HD controls were identified. HCRU in 6 months post-index was significantly greater in people with HD compared with non-HD controls for all health care service categories; P < 0.0001. The mean number of HCRU PPPM for all measured healthcare services was significantly higher in people with HD compared with non-HD controls (P < 0.001). Mean total costs (2018 USD PPPM) for the HD cohort ($2,260 [SD = $4,682]) were twice the total costs in the non-HD cohort ($1,056 [SD = $3,078]) (P < 0.0001) and were highest across all disease stages. CONCLUSIONS: This study provides current comprehensive HCRU and cost estimates in individuals with HD relative to those without the disease, thus demonstrating the high economic burden imposed by HD. DISCLOSURES: Dr Ta: Employment with Genentech (at time of study) and stock options with Roche; Dr To: Employment and stock options/dividends with Genentech; Dr Patel: Employment and stock options with Roche/Genentech; Dr Fuller: Employment with CHDI Management/CHDI Foundation; Mr Surinach: Employment with Genesis Research (which receives consulting fees from Genentech/Roche); Dr Abbass: Employment and stock options with Genentech; Dr Exuzides: Employment and stock options with Roche/Genentech; and Ms Luo: Employment with CHDI Management/CHDI Foundation. This study was funded by Genentech Inc. The authors thank Greg Rowe of Chrysalis Medical Communications for providing medical writing support, which was funded by F. Hoffmann-La Roche Ltd, in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Healthcare resource utilization and costs in individuals with Huntington's disease by disease stage in a US population.

AIMS: To quantify healthcare resource utilization (HRU) and costs by disease stage in individuals with Huntington's disease (HD) in a US population. MATERIALS AND METHODS: This retrospective cohort study used administrative claims data from the IBM MarketScan Commercial, Multi-State Medicaid, and Medicare Supplemental Databases between 1 January 2009 and 31 December 2018. Individuals with an HD claim between 1 January 2010 and 31 December 2017 were selected. Index date was the date of first HD diagnosis. Individuals were required to have continuous enrollment for ≥ 12 months pre-index, 3 months post-index, and have no pre-index HD claims. All-cause HRU and costs per patient per month (PPPM) (overall and stratified by disease stage) were assessed for individuals with HD. RESULTS: A total of 2,669 individuals with HD were identified. Of these, 1,432 (53.7%), 689 (25.8%), and 548 (20.5%) had early-, middle-, and late-stage HD at baseline, respectively. Mean HRU PPPM by post-index HD stage increased with disease stage for outpatient visits, pharmacy claims, and HD-related pharmacy claims (p < 0.05 for all). Mean inpatient visits and emergency room visits PPPM were highest in individuals with middle-stage HD (p <0.05 for all). Mean total all-cause healthcare cost PPPM for individuals with HD was $2,889, and it was significantly higher in middle-stage individuals, at $7,988, compared with early- and late-stage individuals, at $3,726 and $5,125, respectively; p <0.0001. LIMITATIONS: In the absence of disease staging information in administrative claims data, staging was based on the presence of clinical markers in claims. Our evaluations didn't include the indirect costs of HD, which may be substantial as HD typically affects people at their peak earning potential. CONCLUSIONS: HRU and costs of care are high among individuals with HD, particularly among those with middle- and late-stage disease. This indicates that the disease burden in HD increases with disease stage, highlighting the need for interventions that can slow or prevent disease progression.

Epidemiology of Huntington's Disease in the United States Medicare and Medicaid Populations.

INTRODUCTION: Huntington's disease (HD) is a rare, genetic, and ultimately fatal neurodegenerative disease, with a devastating impact on individuals and families across generations. Few estimates of HD epidemiology in the United States (US) exist. METHODS: This study employed a retrospective cross-sectional design to examine the epidemiology of HD in the US Medicare and Medicaid beneficiary populations using 2016-2017 claims data from the Medicare 100% Research Identifiable Files (RIFs) and 2014 claims data from the Medicaid Analytic eXtract (MAX) files for 17 states. Medicare beneficiaries ≥65 years with a diagnosis of HD (≥1 claim with ICD-10-CM code G10) in 2017 and Medicaid beneficiaries <65 years with a diagnosis of HD (≥1 claim with ICD-9-CM code 333.4) in 2014 were identified. The study outcomes included the 2017 prevalence proportion and incidence rate of HD in the Medicare population and the 2014 prevalence proportion of HD in the Medicaid population. RESULTS: In the Medicare population, 1,941 prevalent and 819 incident cases of HD were identified in 2017, corresponding to a prevalence proportion of 13.1 per 100,000 persons and incidence rate of 6.1 per 100,000 person-years. In the Medicaid population, 353 prevalent cases of HD were identified in 2014, corresponding to a prevalence proportion of 15.2 per 100,000 persons. CONCLUSION: This study suggests that prevalence and incidence of HD in the US may be higher than previously estimated. This has important implications in raising awareness of HD among providers and payers and ensuring availability of and access to services for HD patients and care partners in the Medicare and Medicaid populations.

Understanding the Burdens Associated with Huntington's Disease in Manifest Patients and Care Partners-Comparing to Parkinson's Disease and the General Population.

BACKGROUND: The study provides real-world data on the impact of Huntington's disease (HD) from the perspective of individuals with HD (IHD) and care partners (HD-CP) and contextualizes these results relative to Parkinson's disease (PD) and the general population (GP). METHODS: Cross-sectional survey of IHD and HD-CP in the US (July 2019-August 2019) conducted using the Rare Patient Voice panel. Data for individuals with Parkinson's Disease (IPD), the general population (GP), and respective care partners (PD-CP; GP-CP) came from the 2018 US National Health and Wellness Survey. Outcomes included demographics, mental health, clinical characteristics, and health-related quality of life (HRQoL). RESULTS: IHD had greater comorbid anxiety (IHD = 51.2%, IPD = 28.8%, GP = 2.0%), and HD-CP had greater comorbid anxiety (HD-CP = 52.5%, PD-CP = 28.6%, GP-CP = 19.6%) and depression (HD-CP = 65.0%, PD-CP = 29.9%, GP-CP = 19.6%), relative to other cohorts (p < 0.05). Respective of their GP cohorts, IHD exhibited lower HRQoL (EQ-5D: 0.66 ± 0.21 vs. 0.81 ± 0.17) and greater depression (PHQ-9: 11.59 ± 7.20 vs. 5.85 ± 6.71), whereas HD-CP exhibited greater depression only (PHQ-9: 6.84 ± 6.38 vs. 4.15 ± 5.58) (p < 0.001). No differences were observed between HD/HD-CP and PD/PD-CP cohorts on PHQ-9 or HRQoL. CONCLUSIONS: HD has a significant burden on patients and care partners, which is higher than GP. Notably, anxiety and depression were greater among HD vs. PD, despite similar HRQoL.

Healthcare utilization and cost burden of Huntington's disease among Medicare beneficiaries in the United States.

AIMS: To examine healthcare utilization and costs in a US Medicare population diagnosed with Huntington's disease (HD). METHODS: This was a retrospective matched cohort study using Medicare fee-for-service (FFS) claims data using 2013-2017 Research Identifiable Files. Medicare beneficiaries diagnosed with HD based on the presence of at least one medical claim with an International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification (ICD-9/10-CM) diagnosis code for HD (ICD-9-CM: 333.4; ICD-10-CM: G10) during the identification period (2014-2016). Beneficiaries without HD were drawn from a 5% random sample of Medicare beneficiaries and 1:1 matched to those with HD for comparison. All-cause and HD-related (any utilization related to HD diagnosis or symptoms associated with HD) healthcare utilization and costs were reported. RESULTS: We identified 3,688 matched pairs of beneficiaries with and without HD. Of those with HD, 1,922 (52.1%) were late-stage, 916 (24.8%) were middle-stage, and 850 (23.1%) were early-stage. Mean [SD] annual total healthcare costs were higher for HD beneficiaries than beneficiaries without HD ($41,631 [57,393] vs. $17,222 [31,218], p < .001) and were primarily driven by outpatient pharmacy costs ($19,182 [45,469] vs. $4,318 [11,553], p < .001). In the stratified analysis, total healthcare costs were highest among beneficiaries with late-stage HD (mean [SD] cost: $20,475 [$41,122] for early-stage vs. $29,733 [$44,977] for middle-stage vs. $56,657 [$64,185] for late-stage; p < .001). LIMITATIONS: Results are not generalizable to beneficiaries enrolled in other non-FFS Medicare plans. Administrative claims are intended for billing purposes, not research, and may not capture all symptoms, comorbidities, and other adverse events. CONCLUSIONS: This original, comprehensive analysis of healthcare utilization and economic burden among Medicare beneficiaries with HD found that healthcare needs and associated costs are substantially higher among Medicare beneficiaries who are diagnosed with HD compared to beneficiaries without HD.

Estimating the risk of thrombotic events in people with congenital hemophilia A using US claims data.

Aim: Compare thrombotic risk in people with congenital hemophilia A (PwcHA) to the general non-hemophilia A (HA) population. Patients & methods: US claims databases were analyzed to identify PwcHA. Incidence rates of myocardial infarction, pulmonary embolism, ischemic stroke, deep vein thrombosis and device-related thrombosis were compared with a matched cohort without HA. Results: Over 3490 PwcHA were identified and 16,380 individuals matched. PwcHA had a similar incidence of myocardial infarction and pulmonary embolism compared with the non-HA population, but a slightly higher incidence of ischemic stroke and deep vein thrombosis. The incidence of device-related thrombosis was significantly higher in PwcHA. Conclusion: This analysis suggests that PwcHA are not protected against thrombosis, and provides context to evaluate thrombotic risk of HA treatments.

Variation in access to hemophilia A treatments in the United States.

BACKGROUND: US commercial health plans have been found to vary in how they cover specialty drugs indicated for a range of diseases. In this study, we examined patients' access to hemophilia A (HemA) treatments across a set of large commercial health plans. OBJECTIVE: To examine variation in health plans' coverage policies for HemA treatments. METHODS: We reviewed HemA treatment coverage policies (current as of August 2019) issued by 17 commercial health plans primarily using the Tufts Medical Center Specialty Drug Evidence and Coverage Database. We categorized policies as: covered without conditions (coverage consistent with the FDA label); covered with conditions (conditions on coverage beyond the FDA label); broader coverage (coverage for a broader patient population than the FDA label); and mixed (conditions on coverage beyond the FDA label in one way, but coverage was broader than the FDA label in another). RESULTS: We identified 296 coverage policies for 26 HemA treatments, including 15 short half-life factor VIII (FVIII) products, five extended half-life FVIII products, three bypassing agents, two desmopressin products, and emicizumab. We classified 36% of policies as coverage without conditions, 50% as covered with conditions, 7% as broader coverage, and 7% as mixed. Plans applied conditions on coverage with different frequencies: two did not apply conditions in any policies; ten applied conditions in ≥50%; four applied conditions in <40%. One plan did not publish coverage policies for any HemA products. Conditions on coverage most often related to bleeding frequency (36%), although specific requirements varied. Plans applied step therapy protocols in 17% of policies. CONCLUSIONS: How health plans covered HemA treatments varied. Plans added conditions on coverage beyond the FDA label roughly half the time. Conditions most often related to bleeding frequency. Variable coverage affects patients' access to treatment, and potentially has clinical implications on disease management and disease progression.

Real-world treatment, clinical outcomes and healthcare resource utilization among persons with hemophilia A by age.

Aim: Examine real-world characteristics, treatment patterns, and outcomes among treated persons with hemophilia A (PwHA) stratified by age. Patients & methods: This study utilized US claims data from 1 January 2007-31 July 2018 from the Humana Research Database. Unadjusted comparisons were conducted across PwHA (<18, 18-55, 56-89 years) enrolled in commercial or Medicare Advantage Prescription Drug plans. Results: A total of 294 PwHA were identified; 21.1% experienced ≥1 bleeding event, and 41.2 and 53.1% had evidence of arthropathy or related disorders, and pain, respectively. Along with all-cause and hemophilia-related healthcare resource utilization (HCRU), these were highest among PwHA aged 56-89 years. Conclusion: Insights into treatment, outcomes and HCRU may identify opportunities for enhanced disease management, particularly in older PwHA.

Economic burden of pediatric prescription opioid poisonings in the United States.

BACKGROUND: Among the different drugs involved in pediatric exposures and poisonings, opioids are the most important, given their rise in nonmedical use. Opioid poisonings in children can result in serious symptoms or complications, including respiratory disorders such as apnea, respiratory failure, and respiratory depression; psychiatric or nervous system disorders such as agitation, seizures, and coma; and cardiac disorders such as tachycardia, bradycardia, and cardiac arrest. Opioid poisonings in children can have delayed onset of symptoms as well as severe and prolonged toxic effects. Many studies have examined the economic burden of opioid poisoning in the general population, but very little is known about the pediatric population. OBJECTIVE: To estimate the economic burden associated with pediatric prescription opioid poisonings. METHODS: This study examined opioid poisonings in pediatric patients, defined as patients aged less than 18 years, for the 2012 base year. Costs were estimated using the 2012 Nationwide Emergency Department Sample (NEDS), Kids' Inpatient Database (KID), Multiple Cause-of-Death (MCOD) file, and other published sources, while applying a societal perspective. The Bottom Up approach was used to estimate the total cost of pediatric prescription opioid poisonings. Direct costs included costs associated with emergency department (ED) visits, hospitalizations, and ambulance transports. Indirect costs were estimated using the human capital method and included productivity costs due to caregivers' absenteeism and premature mortality among children. Descriptive statistics were employed in calculating costs. RESULTS: The total costs of pediatric prescription opioid poisonings and exposure in the United States were $230.8 million in 2012. Total direct costs were estimated to be over $21.1 million, the majority resulting from prescription opioid poisoning-related inpatient stays. Total indirect (productivity) costs were calculated at $209.7 million, and 98.6% of these costs were attributed to opioid poisoning-related mortality. Pediatric prescription opioid poisoning-related ED visits, inpatient stays, and deaths were most common in patients aged 13-17 years and those in mid to large urban areas. Most were unintentional. CONCLUSIONS: Pediatric prescription opioid poisonings resulted in direct and indirect costs of $230.8 million in 2012. While these costs are low in comparison with the costs of prescription opioid poisoning in the general population, the number of pediatric poisonings represents only a small fraction of total poisonings. Quantified costs associated with pediatric prescription opioid poisonings can help decision makers to understand the economic trade-offs in planning interventions. DISCLOSURES: This research had no external funding but was funded by an unrestricted research grant made to the Department of Pharmacotherapy & Outcomes Science by kaléo Pharma, maker of a naloxone product. The authors declare no conflicts of interest or financial interests. Portions of this study were presented as an abstract at the 22nd Annual ISPOR Meeting; May 22, 2017; Boston, MA.

Model of Short- and Long-Term Outcomes of Emicizumab Prophylaxis Treatment for Persons with Hemophilia A.

BACKGROUND: Hemophilia A (HA) can result in bleeding events because of low or absent clotting factor VIII (FVIII). Prophylactic treatment for severe HA includes replacement FVIII infusions and emicizumab, a bispecific factor IXa- and factor X-directed antibody. OBJECTIVE: To develop an economic model to predict the short- and long-term clinical and economic outcomes of prophylaxis with emicizumab versus short-acting recombinant FVIII among persons with HA in the United States. METHODS: A Markov model was developed to compare clinical outcomes and costs of emicizumab versus FVIII prophylaxis among persons with severe HA from U.S. payer and societal perspectives. Patients started prophylaxis at age 1 year in the base case. Mutually exclusive health states considered were "no arthropathy," "arthropathy," "surgery," and "death." Serious adverse events, breakthrough bleeds, and inhibitor development were simulated throughout the modeled time horizon. In addition to the prophylaxis drug costs, patients could incur other direct costs related to breakthrough bleeds treatment, serious adverse events, development of inhibitors, arthropathy, and orthopedic surgery. Indirect costs associated with productivity loss (i.e., missed work or disabilities) were applied for adults. Model inputs were obtained from the HAVEN 3 trial, published literature, and expert opinion. The model used a lifetime horizon, and results for 1 year and 5 years were also reported. Deterministic sensitivity analyses and scenario analyses were conducted to assess robustness of the model. RESULTS: Over a lifetime horizon, the cumulative number of all treated bleeds and joint bleeds avoided on emicizumab versus FVIII prophylaxis were 278.2 and 151.7, respectively. Correspondingly, arthropathy (mean age at onset: 12.9 vs. 5.4 years) and FVIII inhibitor development (mean age at development: 13.9 vs. 1.1 years) were delayed. Total direct and indirect costs were lower for emicizumab versus FVIII prophylaxis for all modeled time horizons ($97,159 vs. $331,610 at 1 year; $603,146 vs. $1,459,496 at 5 years; and $15,238,072 vs. $22,820,281 over a lifetime horizon). The sensitivity analyses indicated that clinical outcomes were sensitive to efficacy inputs, while economic outcomes were driven by the discount rate, dosing schedules, and treatments after inhibitor development. Results for moderate to severe patients were consistent with findings in the severe HA population. CONCLUSIONS: The model suggests that emicizumab prophylaxis confers additional clinical benefits, resulting in a lower number of bleeding events and delayed onset of arthropathy and inhibitor development across all time assessment horizons. Compared with short-acting recombinant FVIII, emicizumab prophylaxis leads to superior patient outcomes and cost savings from U.S. payer and societal perspectives. DISCLOSURES: Funding for this study was provided by Genentech. Raimundo and Patel are employees of Genentech and own stock or stock options. Zhou, Han, Ji, Fang, Zhong, and Betts are employees of Analysis Group, which received consultancy fees from Genentech for conducting this study. Mahajerin received consultancy fees from Genentech for work on this study. Portions of this research were presented as a poster at the 2018 American Society of Hematology Conference; December 1-4, 2018; San Diego, CA.

Economic impact model of delayed inhibitor development in patients with hemophilia a receiving emicizumab for the prevention of bleeding events.

Aims: Cumulative exogenous factor VIII (FVIII) exposure is an important predictor of developing neutralizing antibodies (inhibitors) to FVIII in patients with persons with hemophilia A (PwHA). The aim of this study was to model the costs of emicizumab versus FVIII prophylaxis and total treatment costs for patients with severe HA.Materials and Methods: An Excel-based decision model was developed to calculate cumulative costs in PwHA over a 20-year time horizon from the US payer perspective. The model considered persons with severe HA beginning at age 12 months with no prior FVIII exposure and initiating prophylaxis with emicizumab or FVIII. PwHA could develop inhibitors on accumulation of 20 FVIII exposure days. PwHA with inhibitors replaced FVIII with bypassing agents until inhibitors resolved spontaneously, following immune tolerance induction (ITI), or at the end of the time horizon. The primary model outcome was the difference in emicizumab versus FVIII treatment costs in 2019 USD. Sensitivity analyses were performed to test the robustness of results.Results: Total incremental cost over 20 years was -$1,945,480 (emicizumab arm, $4,919,058; FVIII arm, $6,864,538). Prophylaxis costs (emicizumab arm, $4,096,105; FVIII arm, $6,290,919) comprised the majority of costs in both groups, followed by breakthrough bleed treatment for the FVIII arm ($342,652) and ITI costs for the emicizumab arm ($733,671). Higher costs in the FVIII group reflected earlier inhibitor development (FVIII, 4 months; emicizumab, 162 months) and switch to bypassing agents.Limitations: The model design reflects a simplified treatment pathway for patients with severe HA who initiate FVIII or emicizumab prophylaxis. In the absence of clinical data, a key conservative assumption of the model is that patients receiving emicizumab and FVIII prophylaxis have the same risk of developing inhibitors.Conclusions: This study suggests that prophylaxis with emicizumab results in cost savings compared to FVIII prophylaxis in HA.

Prevalence and Characteristics of Pediatric Opioid Exposures and Poisonings in the United States.

OBJECTIVE: To examine the prevalence and characteristics of pediatric opioid exposures and poisonings in the US. STUDY DESIGN: This was a retrospective, cross-sectional analysis using the National Poison Data System from January 1, 2010 to December 31, 2014. Records of children aged <18 years with exposure to opioid-containing medications were identified. Standardized prevalence rates were calculated, and the annual trend was examined. Pediatric opioid exposures were characterized descriptively, and logistic regression was performed to estimate the association between various clinical and sociodemographic characteristics and exposures with serious (ie, moderate, major, or death) outcomes. The association of pediatric opioid exposures and area-level socioeconomic status factors at 5-digit ZIP code level was examined descriptively. RESULTS: The prevalence of opioid exposures was 22.6 per 100 000 children and was particularly high among ≤5-year-olds. Prevalence declined from 25.5 to 20 per 100 000 children from 2010 to 2014. There were 83 418 pediatric opioid exposures over the 5-year period and nearly one-half resulted in poisoning. Over 60% of exposures were among children ≤5 years of age, 73.4% were unintentional, and over 90% occurred at home. One in every 2 pediatric opioid exposures was evaluated in a healthcare facility. Annually 4912 children aged ≤5 years were treated in the emergency department or admitted for care. Older age, nonaccidental intent, and single-substance opioid, especially buprenorphine and methadone, were associated with serious outcomes (P < .05). Positive correlations were observed for area-level socioeconomic status factors including proportion of adults and pediatric opioid exposures. CONCLUSIONS: Pediatric opioid exposures and poisonings decreased from 2010 to 2014 but morbidity remains high. The epidemiology of opioid exposures differed considerably by age.

A Comparison of Pharmacy Dispensing Channel Use and Adherence to Specialty Drugs Among Medicare Part D Beneficiaries.

BACKGROUND: Nonadherence to specialty drugs has been associated with poor clinical and economic outcomes. Studies conducted using commercial health plans suggest that patients who use specialty pharmacies have higher adherence compared with patients using retail pharmacies. However, little is known about the frequency of dispensing channel use or the association of dispensing channel use with adherence to specialty drugs among Medicare Part D beneficiaries. OBJECTIVES: To (a) describe the use of pharmacy dispensing channels by patients using self-administered specialty drugs in Medicare Part D and (b) study the association between dispensing channel use and adherence to specialty drugs in this population. METHODS: This study analyzed 2010 Medicare Part D data. Specialty drugs were defined as drugs with a mean cost ≥ $600 per month. We identified the top 13 specialty medications by cost and classified patients into the following classes: anticancer, disease-modifying therapy (DMT), and tumor necrosis factor inhibitor (TNFi). Dispensing channels included retail, specialty, mail order, long-term care, and other. We included patients continuously enrolled in Medicare Part D who had ≥ 1 prescription for a specialty medication before the end of June 2010. These patients were followed until the end of 2010. Patients with proportion of days covered (PDC) ≥ 0.8 were considered adherent. Adherence rates were calculated by weighting for therapeutic class after weighting for drug mix. Multivariable logistic regression analysis examined the association between dispensing channel and adherence. RESULTS: Of 5,430 patients, 1,248 were dispensed anticancer medications, 1,723 were dispensed DMTs, and 2,459 were dispensed TNFi drugs. About 16% used specialty, 74% used retail, 4% used mail order, 4% used long-term care, and 3% used other channels. The distribution pattern was similar when stratified by therapeutic class. In the descriptive analysis, patients using the specialty channel for the anticancer and TNFi classes had 7% and 10% higher adherence rates, respectively, compared with retail. For the DMT class, the adherence rate was higher for mail order but similar for retail and specialty channels. Adjusted analysis found that overall, specialty users had 23% higher odds for being adherent compared with retail users (P = 0.0104). For the anticancer and TNFi classes, specialty users had 39% (P = 0.0311) and 55% (P = 0.0005) higher odds, respectively, for being adherent than retail users. For the DMT class, no significant association was observed between dispensing channel and adherence (P = 0.9691). CONCLUSIONS: Nearly three quarters of Medicare patients on specialty therapies included in this study used the retail channel compared with one sixth who used the specialty channel. Overall, specialty channel use was associated with higher adherence compared with retail channel use. However, this relationship varied by therapeutic class. The specialty channel was associated with higher adherence among patients from the anticancer and TNFi classes but not among the DMT class. DISCLOSURES: No funding supported this study. The authors reported no potential conflicts of interest. Kale, Patel, and Carroll were responsible for study concept and design. Data analysis was conducted by Kale, assisted by Patel. The manuscript was written primarily by Kale, with assistance from Carroll. Some findings from this study were presented during the poster presentation at the Academy of Managed Care Pharmacy Nexus held in National Harbor, Maryland, on October 4, 2016.

Prescription opioid abuse: a literature review of the clinical and economic burden in the United States.

Between 2002 and 2007, the nonmedical use of prescription pain relievers grew from 11.0 million to 12.5 million people in the United States. Societal costs attributable to prescription opioid abuse were estimated at $55.7 billion in 2007. The purpose of this study was to comprehensively review the recent clinical and economic evaluations of prescription opioid abuse. A comprehensive literature search was conducted for studies published from 2002 to 2012. Articles were included if they were original research studies in English that reported the clinical and economic burden associated with prescription opioid abuse. A total of 23 studies (183 unique citations identified, 54 articles subjected to full text review) were included in this review and analysis. Findings from the review demonstrated that rates of opioid overdose-related deaths ranged from 5528 deaths in 2002 to 14,800 in 2008. Furthermore, overdose reportedly results in 830,652 years of potential life lost before age 65. Opioid abusers were generally more likely to utilize medical services, such as emergency department, physician outpatient visits, and inpatient hospital stays, relative to non-abusers. When compared to a matched control group (non-abusers), mean annual excess health care costs for opioid abusers with private insurance ranged from $14,054 to $20,546. Similarly, the mean annual excess health care costs for opioid abusers with Medicaid ranged from $5874 to $15,183. The issue of opioid abuse has significant clinical and economic consequences for patients, health care providers, commercial and government payers, and society as a whole.

Modeling the Frequency and Costs Associated with Postsurgical Gastrointestinal Adverse Events for Tapentadol IR versus Oxycodone IR.

BACKGROUND: Few studies have estimated the economic effect of using an opioid that is associated with lower rates of gastrointestinal (GI) adverse events (AEs) than another opioid for postsurgical pain. OBJECTIVE: To estimate the number of postsurgical GI events and incremental hospital costs, including potential savings, associated with lower GI AE rates, for tapentadol immediate release (IR) versus oxycodone IR, using a literature-based calculator. METHODS: An electronic spreadsheet-based cost calculator was developed to estimate the total number of GI AEs (ie, nausea, vomiting, or constipation) and incremental costs to a hospital when using tapentadol IR 100 mg versus oxycodone IR 15 mg, in a hypothetical cohort of 1500 hospitalized patients requiring short-acting opioids for postsurgical pain. Data inputs were chosen from recently published, well-designed studies, including GI AE rates from a previously published phase 3 clinical trial of postsurgical patients who received these 2 opioids; GI event-related incremental length of stay from a large US hospital database; drug costs using wholesale acquisition costs in 2011 US dollars; and average hospitalization cost from the 2009 Healthcare Cost and Utilization Project database. The base case assumed that 5% (chosen as a conservative estimate) of patients admitted to the hospital would shift from oxycodone IR to tapentadol IR. RESULTS: In this hypothetical cohort of 1500 hospitalized patients, replacing 5% of oxycodone IR 15-mg use with tapentadol IR 100-mg use predicted reductions in the total number of GI events from 1095 to 1085, and in the total cost of GI AEs from $2,978,400 to $2,949,840. This cost reduction translates to a net savings of $22,922 after factoring in drug cost. For individual GI events, the net savings were $26,491 for nausea; $12,212 for vomiting; and $7187 for constipation. CONCLUSION: Using tapentadol IR in place of a traditional µ-opioid shows the potential for reduced GI events and subsequent cost-savings in the postsurgical hospital setting. In the absence of sufficient real-world data, this literature-based cost calculator may assist hospital Pharmacy & Therapeutics committees in their evaluation of the costs of opioid-related GI events.