Sodium phenylbutyrate-taurursodiol access, adherence and adverse event in patients with amyotrophic lateral sclerosis: Experience at one center in the United States.

INTRODUCTION/AIMS: Sodium phenylbutyrate-taurursodiol (PB-TURSO) was recently approved for treating amyotrophic lateral sclerosis (ALS). Third-party payors' coverage policies are evolving, and adverse events are just being fully assessed. The goals of this study were to evaluate patients' experiences in obtaining and continuing PB-TURSO and assess adverse events and medication adherence. METHODS: Medical records of 109 ALS patients who were considered PB-TURSO candidates by the treating physician at a tertiary ALS clinic from October 2022 to May 2023 were reviewed. Data was recorded for demographics, clinical, and insurance information. A survey was e-mailed to patients asking about out-of-pocket expenses for PB-TURSO, financial assistance, medication start and (if applicable) stop dates, and reasons for discontinuation. RESULTS: Insurance information was available for 91 patients [57 males (62%); mean age 64.8 years (range 25.7-88)]. Of 79 who applied for insurance approval, 71 (90%) were approved; however, 19 required 1-3 appeals. Among 73 patients with available data about medication status, 54 started PB-TURSO and 19 did not, most commonly due to personal choice or out-of-pocket expenses. About 44% of patients (24/54) stopped taking PB-TURSO, primarily due to adverse events. Monthly out-of-pocket expenses varied from $0 to $3500 and 36 patients qualified for financial assistance. Administrative and nursing staff devoted 7.2 hours/week to the insurance authorization process. DISCUSSION: Most patients received insurance approval for PB-TURSO, but one-fourth required appeals. Some out-of-pocket costs were very high. Investment of staff time was substantial. These findings have implications for insurance coverage of, and adherence to, future ALS treatments.

A Model-Based Economic Evaluation of Hypothetical Treatments for Amyotrophic Lateral Sclerosis in the UK: Implications for Pricing of New and Emerging Health Technologies.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating disease which leads to loss of muscle function and paralysis. Historically, clinical drug development has been unsuccessful, but promising disease-modifying therapies (DMTs) may be on the horizon. OBJECTIVES: The aims of this study were to estimate survival, quality-adjusted life-years (QALYs) and costs under current care, and to explore the conditions under which new therapies might be considered cost effective. METHODS: We developed a health economic model to evaluate the cost effectiveness of future ALS treatments from a UK National Health Service and Personal Social Services perspective over a lifetime horizon using data from the ALS-CarE study. Costs were valued at 2021/22 prices. Two hypothetical interventions were evaluated: a DMT which delays progression and mortality, and a symptomatic therapy which improves utility only. Sensitivity analysis was conducted to identify key drivers of cost effectiveness. RESULTS: Starting from King's stage 2, patients receiving current care accrue an estimated 2.27 life-years, 0.75 QALYs and lifetime costs of £68,047. Assuming a 50% reduction in progression rates and a UK-converted estimate of the price of edaravone, the incremental cost-effectiveness ratio for a new DMT versus current care is likely to exceed £735,000 per QALY gained. Symptomatic therapies may be more likely to achieve acceptable levels of cost effectiveness. CONCLUSIONS: Regardless of efficacy, DMTs may struggle to demonstrate cost effectiveness, even at a low price. The cost effectiveness of DMTs is likely to be strongly influenced by drug price, the magnitude and durability of relative treatment effects, treatment starting/stopping rules and any additional utility benefits over current care.

Capitalizing on Hope: Questionable Marketing Approval and Pricing of a New ALS Drug.

Regulatory agencies must balance patient demands to access new treatments for fatal diseases with limited treatment options while ensuring drug safety and efficacy. However, questionable U.S. regulatory actions resulted in the early approval of AMX0035 to treat amyotrophic lateral sclerosis (ALS) by reconvening advisory commissions to obtain positive decisions and designating the drug as a new molecular entity. Data from one randomized clinical trial suggests minimal delays in disease progression and longer survivability, but debate remains about the lack of confirmatory evidence of effectiveness owing to study limitations. A patient's decision-making process details the experience of using the drug, including perspectives on access, cost, effectiveness, and adverse effects. In line with the "nichebuster" business model, the drugmaker, Amylyx Pharmaceuticals, is charging US$158,000/year/patient and thus forecast to turn a profit on a drug with debatable clinical effectiveness prior to completing a Phase 3 trial. Early marketing approval, despite community demands, is unnecessary and may have reduced access because of the end of a compassionate use program, and the high price tag results in restricted coverage and high out-of-pocket costs. Also, the drug's key ingredients are available as a generic and a supplement.

Medical cost and healthcare utilization of amyotrophic lateral sclerosis in China: A cohort study based on hospital data from 2015 to 2018.

Amyotrophic lateral sclerosis (ALS), a specific neurodegenerative disease, imposed increased economic and utilizations burden on the healthcare system, especially with the progress of the diseases severity. However, the economic burden on Chinese ALS patients remained unclear. This study therefore was aimed to investigate medical cost and healthcare utilization for Chinese ALS patients.Longitudinal health data of over 20 million individuals, including military personnel and civilians, was collected from all Chinese military hospitals. We identified 480 patients with a first major diagnosis for ALS from 2015 to 2018, while matched 400 controlled patients on age, gender, ethnic group, geographic region, length of stay, year of diagnosis and comorbidity. Their medical cost and healthcare utilizations were then measured 1 year before, and 1 year after ALS diagnosis.The median annual medical cost of ALS patients was about 2-fold higher, 17,087 CNY during the index year than 1 year before, 7859 CNY. The highest increase in utilizations may account for medical costs on ALS patients, which was represented by hospitalizations (Odd Ratio (OR) = 4.26, 95% confidence interval (CI) 3.52, 5.15), electromyography (OR = 4.14, 95% CI 2.37, 7.22), nerve conduction velocity (OR = 3.26, 95% CI 2.23, 4.77).This study is the first one reporting direct economic burden on Chinese ALS patients. Efforts should be made to develop cost-effective diagnostic tools in order that sources of medical cost were more effectively allocated, and this disease was detected earlier.

A Cost-Effectiveness Framework for Amyotrophic Lateral Sclerosis, Applied to Riluzole.

OBJECTIVES: Reexamine cost-effectiveness of riluzole in the treatment of amyotrophic lateral sclerosis (ALS) in light of recent advances in disease staging and understanding of stage-specific drug effect. METHODS: ALS was staged according to the "fine'til 9" (FT9) staging method. Stage-specific health utilities (EQ-5D, US valuation) were estimated from an institutional cohort, whereas literature informed costs and transition probabilities. Costs at 2018 prices were disaggregated into recurring costs (RCs) and "one-off" transition/"tollgate" costs (TCs). Five- and 10-year horizons starting in stage 1 disease were examined from healthcare sector and societal perspectives using Markov models to evaluate riluzole use, at a threshold of $100 000/quality-adjusted life year (QALY). Probabilistic and deterministic sensitivity analyses were conducted. RESULTS: Mean EQ-5D utilities for stages 0 to 4 were 0.79, 0.74, 0.63, 0.54, and 0.46, respectively. From the healthcare sector perspective at the 5-year horizon, riluzole use contributed to 0.182 QALY gained at the cost difference of $12 348 ($5403 riluzole cost, $8870 RC and -$1925 TC differences), translating to an incremental cost-effectiveness ratio (ICER) of $67 658/QALY. Transition probability variation contributed considerably to ICER uncertainty (-30.2% to +90.0%). ICER was sensitive to drug price and RCs, whereas higher TCs modestly reduced ICER due to delayed tollgates. CONCLUSION: This study provides a framework for health economic studies of ALS treatments using FT9 staging. Prospective stage-specific and disaggregated cost measurement is warranted for accurate future cost-effectiveness analyses. Appropriate separation of TCs from RCs substantially mitigates the high burden of background cost of care on the ICER.

Healthcare provision in amyotrophic lateral sclerosis: procedures, queries and pitfalls in Germany and Poland.

There are a number of physical restrictions that develop in the course of amyotrophic lateral sclerosis (ALS). While loss of speech and motor control may be partially compensated by the support of assistive devices, swallowing difficulty and respiratory insufficiency require medical interventions (percutaneous endoscopic gastrostomy, noninvasive, and invasive ventilation). Based on the data collected within the NEEDSinALS study, we found major differences in personal satisfaction with the financing, healthcare provision, medical infrastructure, and regulations of German and Polish ALS patients, despite minor differences in economic burden caused by the disease. In order to explain this phenomenon, we thoroughly reviewed the legal basis, structure and organization of the healthcare systems in Germany and Poland to determine the range of obstacles in the everyday lives of patients and their caregivers that are attempting to attain an assistive device or care after the start of medical interventions.

Dying of amyotrophic lateral sclerosis: Health care use and cost in the last year of life.

OBJECTIVE: To describe health care service utilization and cost for decedents with and without amyotrophic lateral sclerosis (ALS) in the last year of life. METHODS: Using linked health administrative data, we conducted a retrospective, population-based cohort study of Ontario, Canada, decedents from 2013 to 2015. We examined demographic data, rate of utilization, and cost of health care services in the last year of life. RESULTS: We identified 283,096 decedents in Ontario, of whom 1,212 (0.42%) had ALS. Decedents with ALS spent 3 times as many days in an intensive care unit (ICU) (mean 6.3 vs 2.1, p < 0.001), and twice as many days using complex continuing care (mean 12.7 vs 6.0, p < 0.001) and home care (mean 99.1 vs 41.3, p < 0.001). A greater percentage of decedents with ALS received palliative home care (44% vs 20%, p < 0.001) and palliative physician home visits (40% vs 18%, p < 0.001) than decedents without ALS. Among decedents with ALS, a palliative physician home visit in the last year of life was associated with reduced adjusted odds of dying in hospital (odds ratio 0.65, 95% confidence interval 0.48-0.89) and fewer days spent in the ICU. Mean cost of care in the last year of life was greater for those with ALS ($68,311.98 vs $55,773.48, p < 0.001). CONCLUSIONS: In this large population-based cohort of decedents, individuals with ALS spent more days in the ICU, received more community-based services, and incurred higher costs of care in the last year of life. A palliative care physician home visit was associated with improved end of life outcomes; however, the majority of patients with ALS did not access such services.

Health Utilities and Costs for Motor Neurone Disease.

BACKGROUND: Motor neurone disease (MND) places a significant burden on patients, their carers, and healthcare systems. OBJECTIVES: To estimate health utilities and costs of MND within the UK setting. METHODS: Patients with MND, recruited via 22 regional clinics, completed a postal questionnaire of a cost and quality-of-life survey. Health outcome assessment included the EuroQoL (EQ)-5D-5L, EQ-5D-visual analogue scale, Amyotrophic Lateral Sclerosis Utility Index, and the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised. Clinical staging was based on the Kings and Milano-Torino (MiToS) systems. The questionnaire asked about patients' use of primary, secondary, and community care services in the previous 3 months. Variability in total costs was examined using regression models. RESULTS: 595 patients were included in the health utility analysis, of whom 584 patients also completed a resource use questionnaire. Mean health utility decreased and costs increased between consecutive Kings stages, from 0.76 (95% CI 0.71-0.80) and £1096 (£757-£1240) in Kings stage 1, to 0.50 (0.45-0.54) and £3311 (£2666-£4151) in stage 4, respectively. The changes by MiToS stages were from 0.71 (0.69-0.73) and £1115 (£937-£1130) in MiToS stage 0, to 0.25 (0.07-0.42) and £2899 (£2190-£3840) in stage 2. Kings stages 3 and 4 and MiToS stages 1 and 2, respectively, were significant in explaining variability in total costs. CONCLUSIONS: The impact of MND on health utilities and costs differs by disease severity. The data provided here can be used in cost-effectiveness analyses and to inform decision-making regarding healthcare provision for people with MND.

Current status and direct medical cost of amyotrophic lateral sclerosis in the region of Catalonia: A population-based analysis.

INTRODUCTION: Amyotrophic lateral sclerosis is a neurodegenerative disease that leads to motor weakness. There is no cure, and treatment focuses on slowing down progression, which is achieved by a multidisciplinary approach. Hence, it is vital to understand the population needs for an optimal management of the disease. OBJECTIVES: To evaluate the current status of amyotrophic lateral sclerosis in the region of Catalonia, how the disease is managed and its direct medical costs. METHODS: Records corresponding to 841 patients diagnosed between the year 2007 and 2017 were analysed in a retrospective population-based study, including data from primary care centres, hospitals (inpatient and outpatient care), extended care facilities and mental health centres. RESULTS: Mean diagnosis age was 66.11 years (SD = 12.61) and 52.79% of admitted patients were males. On average, 14.91 months elapsed between diagnosis and death, and the mean age of death was 72.64 years (SD = 12.00). Patients were admitted 10.70 times per year, mostly into primary care (86.50%), although most expenses were concentrated in hospital inpatient care. The mean cost per patient per year was €1,168. The 83.24% of patients had more than 4 systems affected by chronic conditions. CONCLUSIONS: Primary care is of utmost importance in ALS attention in Catalonia, which may have a direct impact in reducing hospitalisation costs. Nonetheless, the expenses linked to inpatient care represent the biggest portion of total costs. Patients' healthcare usage patterns and the high proportion of patients with multiple chronic conditions should be taken into account in order to adapt and improve guidelines and healthcare systems.

Adjusted cost analysis of video televisits for the care of people with amyotrophic lateral sclerosis.

INTRODUCTION: We previously reported our amyotrophic lateral sclerosis (ALS) video televisit experience. Here we report on video televisit versus in-clinic costs, adjusting for perceived medical usefulness (MU). METHODS: We take the patient-perspective and a focused institutional-perspective. Costs are adjusted for patient/caregiver and physician perceptions of visit MU. The base-case reflects our outpatient ALS practice. RESULTS: In the base-case, from the patient perspective, in-clinic visits cost $1,116 and video televisits cost $89 ($119 after MU-adjustment). From the institutional perspective, clinic visits cost $799, and video televisits cost $354 ($472 after MU-adjustment). Adjusted cost-savings per televisit are $997 (patient) and $327 (institution). Sensitivity analyses on 5 variables accounted for uncertainty in base-case assumptions. CONCLUSIONS: Video televisits provide marked adjusted cost-savings for patients and institutions. Adjusted costs are sensitive to perceived MU of video televisits. Future research should explore the ability of video televisits to reduce healthcare resource usage. Muscle Nerve 60: 147-154, 2019.

Charity financial support to motor neuron disease (MND) patients in Greater London: the impact of patients' socioeconomic status-a cross-sectional study.

OBJECTIVE: There is an immense socioeconomic burden for both the patients with motor neuron disease (MND) and their families. The aim of this study is to evaluate the extent to which the provision offered by the Motor Neurone Disease Association is distributed among patients with MND living in the ethnically and socially diverse area of Greater London, according to the patients' socioeconomic situation and needs. SETTING: Greater London, where age and sex-adjusted prevalence rates of MND in 2016 were calculated. PARTICIPANTS: Prevalent MND cases in Greater London, using anonymised data extracted from the Association's database. EXPOSURE: Demographic and socioeconomic characteristics PRIMARY AND SECONDARY OUTCOME MEASURES: Receiving a Motor Neurone Disease Association grant, and the amount of money received. RESULTS: 396 individuals with amyotrophic lateral sclerosis were detected, the age-specific and sex-specific prevalence of MND was 4.02 per 100 000 inhabitants, higher among men (5.13 per 100 000) than women (3.01 per 100 000). Men were statistically significantly 40% less likely to receive a grant compared with women; among grant recipients, the younger the age of the participant, the higher the size of the grant received. The Index of Multiple Deprivation was not associated with either receiving a grant nor the amount of money received, among recipients. CONCLUSION: Financial support by the Motor Neurone Disease Association is provided across individuals and across boroughs regardless of their socioeconomic circumstances. Differences that benefits women and younger patients were detected.

A retrospective analysis of health care utilization for patients with mitochondrial disease in the United States: 2008-2015.

BACKGROUND: Mitochondrial disease (MD) is a heterogeneous group of disorders characterized by impaired energy production caused by abnormal oxidative phosphorylation. Diagnosis of MD is challenging given the variability in how the disease can affect an individual's neurologic, cardiovascular, ophthalmologic, or gastroenterological systems. This study describes the health care utilization and cost in patients diagnosed with MD. METHODS: This study was a retrospective claims analysis based on data from the Truven Health Analytics MarketScan Database and Milliman's Consolidated Health Cost Guidelines Sources Database. For the purpose of this study the diagnosis of MD was defined by ICD-9-CM (prior to October 2015), and ICD-10-CM (October 2015 or later), and included patients identified between January 1, 2008 to December 31, 2015. ICD-9-CM code of 277.87 (disorders of mitochondrial metabolism) and the ICD-10-CM codes of E88.40, E88.41, E88.42 and E88.49 (mitochondrial metabolism disorders) were used as inclusive criteria. Patients were included if they had at least six months of exposure after the first MD-related claim occurrence, and either one MD claim in the inpatient setting OR two MD claims in an outpatient setting. Claims of MD patients are compared to those of a general insured total member population, as well as to those from multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) patients. RESULTS: During the study period, 3825 patients between the ages of 0 and 15 (pediatric) and 4358 patients 16 years of age and greater (adult) were identified. Total allowed per member per month (PMPM) cost for pediatric patients was $4829 and $3100 for adults, compared with an average of $202 and $486, respectively, for the total member population. The greatest drivers of costs based on allowed claims came from inpatient, surgery, and prescription medications. In the adult population, MD imposes a PMPM cost burden that was comparable to that observed for multiple sclerosis ($3518) and ALS ($3460) patients. CONCLUSIONS: This retrospective claim study highlights the significant differences in the cost of medical care for MD patients compared to those of a general population. Mitochondrial disorders are associated with multisystem disease manifestations and a greater care and cost burden similar to other devastating neuromuscular diseases.

ALS managed care considerations.

As a chronic neurological disorder characterized by the progressive deterioration of neuromuscular function, amyotrophic lateral sclerosis (ALS) renders significant physical, psychological, and emotional tolls on patients, their families, and caregivers. Coupled with and contributing to the severe impact on quality of life are the substantial economic costs, which can be direct and indirect, and personal as well as societal. Understanding the magnitude and specifics of the costs accompanying ALS will provide useful perspectives to pharmacists who treat patients with ALS.

Report by the Spanish Foundation for the Brain on the social impact of amyotrophic lateral sclerosis and other neuromuscular disorders. / Informe de la Fundación Del Cerebro sobre el impacto social de la esclerosis lateral amiotrófica y las enfermedades neuromusculares.

INTRODUCTION: A thorough knowledge of the socioeconomic scope of neuromuscular disease is essential for managing resources and raising social awareness. DEVELOPMENT: Our group reviewed current data on the epidemiology, mortality and dependence rates, and socioeconomic impact of amyotrophic lateral sclerosis and neuromuscular diseases in Spain. We also recorded how neurological care for these patients is organised. CONCLUSIONS: Neuromuscular disorders are a very heterogeneous group of diseases, and some are very rare. These disorders account for between 2.8% and 18% of the total motives for a neurological consultation. In Spain, prevalence and incidence figures for amyotrophic lateral sclerosis are similar to those in other countries; however, figures for patients with other neuromuscular diseases are not known. Since the diseases are chronic, progressive, and debilitating, they cause considerable disability and dependence, which in turn directly affects healthcare and social costs associated with the disease. The costs generated by one patient with amyotrophic lateral sclerosis or Duchenne disease have been calculated at about 50 000 euros per year. Neuromuscular disease shows aetiological, diagnostic, and prognostic complexity, and it requires multidisciplinary management. Follow-up for these patients should be entrusted to specialised units.

Profile of medical care costs in patients with amyotrophic lateral sclerosis in the Medicare programme and under commercial insurance.

OBJECTIVE: To determine amyotrophic lateral sclerosis (ALS)-associated costs incurred by patients covered by Medicare and/or commercial insurance before, during and after diagnosis and provide cost details. METHODS: Costs were calculated from the Medicare Standard Analytical File 5% sample claims data from Parts A and B from 2009, 2010 and 2011 for ALS Medicare patients aged ≥70 years (monthly costs) and ≥65 years (costs associated with disability milestones). Commercial insurance patients aged 18-63 years were selected based on the data provided in the Coordination of Benefits field from Truven MarketScan® in 2008-2010. RESULTS: Monthly costs increased nine months before diagnosis, peaked during the index month (Medicare: $10,398; commercial: $9354) and decreased but remained high post-index. Costs generally shifted from outpatient to inpatient and private nursing after diagnosis; prescriptions and durable medical equipment costs were much higher for commercial patients post-diagnosis. Patients appeared to progress to disability milestones more rapidly as their disease progressed in severity (14.4 months to non-invasive ventilation [NIV] vs. 16.6 months to hospice), and their costs increased accordingly (NIV: $58,973 vs. hospice: $76,179). CONCLUSIONS: For newly diagnosed ALS patients in the U.S., medical costs are substantial and increase rapidly and substantially with each disability milestone.

The path to specialist multidisciplinary care in amyotrophic lateral sclerosis: A population- based study of consultations, interventions and costs.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurological condition that requires coordinated, multidisciplinary clinical management. ALS is prone to misdiagnosis as its signs and symptoms may be non-specific, which may prolong patients' journey to multidisciplinary ALS care. METHODS: Using chart review and national register data, we have detailed the journey of a national cohort of ALS patients (n = 155) from the time of first symptom to presentation at a multidisciplinary clinic (MDC). Key milestones were analysed, including frequency of consultations, clinical interventions, and associated economic cost. RESULTS: A majority of patients was male (60%), 65 years of age and over (54%), and had spinal onset ALS (72%). Time from onset of first symptoms to ALS diagnosis was a mean of 15.1 months (median, 11). There was a mean interval of 17.4 months (median 12.5) from first symptoms to arrival at the MDC, and a mean of 4.09 (median, 4) consultations with health care professionals. Electromyography and nerve conduction studies were among the most common interventions. Direct referral by a general practitioner (GP) to a neurologist was associated with reduced cost, but not reduced diagnostic delay. Bulbar ALS was associated with shorter time from symptom onset to diagnosis. Neurologist consultation in the first three consultations was associated with lower costs prior to the ALS clinic attendance but not a shorter time from first symptom to final diagnosis. Mean cost prior to attending the MDC was €3,486 per patient. CONCLUSIONS: Expedited referral to the multidisciplinary ALS clinic would have reduced costs by an estimated €2,072 per patient. Development of a standardised pathway with early referral to neurology of patients with suspected symptoms of ALS could limit unnecessary interventions and reduce cost of care.