Health and economic impact of the correct diagnosis of transthyretin cardiac amyloidosis in Spain.

Objective: To estimate the health and economic impact of the reduction in mortality and cardiovascular hospitalizations, associated with correct diagnosis of cardiac transthyretin amyloidosis (ATTR-CM), from the Spanish National Health System (NHS) perspective.Methods: A costs and effects analysis were performed (probabilistic Markov model) with time horizons between 1 and 15 years, comparing the correct diagnosis of ATTR-CM versus the non-diagnosis. Transition probabilities were obtained from the ATTR-ACT study (placebo arm) and from the literature. Costs and healthcare resources were obtained from Spanish sources (€ 2019) and from a panel of Spanish clinical experts.Results: After 1, 5, 10 and 15 years, the diagnosis of ATTR-CM would generate a gain of 0.031 (95%CI 0.025; 0.038); 0.387 (95%CI 0.329; 0.435); 0.754 (95%CI 0.678; 0.781) and 0.944 (95%CI 0.905; 0.983) life years per patient, respectively, with savings of € 212 (95%CI € -632; 633), € 2,289 (95%CI € 2,250; 2,517), € 2,859 (95%CI € 2,584; 3,149) and € 2,906 (95%CI € 2,669; 3,450) per patient, respectively, versus the non-diagnosis.Conclusions: Just by correctly diagnosing ATTR-CM, years of life would be gained, cardiovascular hospitalizations would be avoided, and savings would be generated for the NHS, compared to the non-diagnosis of the disease.

Estimating the annual economic burden for the management of patients with transthyretin amyloid polyneuropathy in Spain.

Background: Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal disease associated with substantial burden of illness. Three therapies are approved by the European Medicines Agency for the management of this rare disease. The aim of this study was to compare the total annual treatment specific cost per-patient associated with ATTR-PN in Spain.Methods: An Excel-based patient burden and cost estimator tool was developed to itemize direct and indirect costs related to treatment with inotersen, patisiran, and tafamidis in the context of ATTR-PN. The product labels and feedback from five Spanish ATTR-PN experts were used to inform resource use and cost inputs.Results: Marked differences in costs were observed between the three therapies. The need for patisiran- and inotersen-treated patients to visit hospitals for pre-treatment, administration, and monitoring was associated with increased patient burden and costs compared to those treated with tafamidis. Drug acquisition costs per-patient per-year were 291,076€ (inotersen), 427,250€ (patisiran) and 129,737€ (tafamidis) and accounted for the majority of total costs. Overall, the total annual per-patient costs were lowest for patients treated with tafamidis (137,954€), followed by inotersen (308,358€), and patisiran (458,771€).Conclusions: Treating patients with tafamidis leads to substantially lower costs and patient burden than with inotersen or patisiran.

Diagnostic and lifetime hospital costs of patients suffering from wild-type transthyretin amyloid cardiomyopathy in Denmark.

AIMS: Wild-type transthyretin amyloid cardiomyopathy (ATTRwt) is a fast progressing and fatal disease associated with substantial delays in diagnosis. Between the first symptoms and diagnosis, patients are frequently hospitalized, primarily with cardiac symptoms. After diagnosis, patients continue to experience frequent hospital admissions. The objective of this study was to estimate the Danish diagnostic and lifetime hospital costs associated with the treatment of patients with ATTRwt both before and after they are diagnosed. MATERIALS AND METHODS: We developed a cost model for Danish hospital costs associated with ATTRwt, including the costs of diagnosis, cardiac implants, and hospital admissions covering inpatient hospitalization and outpatient hospital care (ambulatory and emergency services). The number of diagnoses, cardiac implants, inpatient hospitalization and outpatient hospital care were estimated based on published data. Estimates of the unit costs were based on publicly available Danish reference costs. We calculated the total hospital costs covering the median lifespan of patients from onset of symptoms, which is 13 months prior to diagnosis, to 52 months after diagnosis which is the median survival time after diagnosis. RESULTS: The average cost of diagnosing ATTRwt was USD 3,424 per patient; the average costs of cardiac implants were USD 1,851 per patient. Hospital admissions costs totaled USD 3,345 pre-diagnosis and USD 59,449 post-diagnosis per patient, on average. The total diagnostic and lifetime (65 months) hospital costs associated with ATTRwt were USD 68,069. CONCLUSIONS: Caring for patients with ATTRwt places a significant economic burden on the healthcare system. The study emphasizes the cost saving potential for medical interventions in this patient population.

Societal costs and burden of hereditary transthyretin amyloidosis polyneuropathy.

Background: Hereditary transthyretin amyloidosis polyneuropathy (ATTRv-PN) is a rare life-threatening disease that imposes considerable mortality and morbidity associated with increased costs, high social support and productivity losses. This study aims to estimate the societal costs and burden of ATTRv-PN.Methods: A cost-of-illness (COI) and burden of disease model were specified from a societal perspective, using a prevalence-based approach. Direct and indirect costs were included. Healthcare resource use was retrieved from public databases, previous Portuguese studies and the literature. The burden of disease was expressed in terms of disability-adjusted life years (DALYs), as defined by the World Health Organisation.Results: In 2016, the total annual COI of ATTRv-PN in Portugal was 52,502,796€ and the mean cost per patient was 28,152€ (79% direct; 21% indirect costs). Treatments accounted for 52% of total costs, while 0.18% were devoted to disease prevention. A total of 2056 DALYs were lost, 26% due to disability and 74% due to death.Conclusions: Annual costs and burden of ATTRv-PN were considerable but within the range of other rare diseases. Policies and public interventions to prevent and reduce the burden of disease should be prioritised, since patients experience excess morbidity, mortality and total costs will likely increase in the future.

Estimating the fiscal impact of rare diseases using a public economic framework: a case study applied to hereditary transthyretin-mediated (hATTR) amyloidosis.

BACKGROUND: A wide range of rare diseases can have fiscal impacts on government finances that extend beyond expected healthcare costs. Conditions preventing people from achieving national lifetime work averages will influence lifetime taxes paid and increase the likelihood of dependence on public income support. Consequently, interventions that influence projected lifetime work activity, morbidity and mortality can have positive and negative fiscal consequences for government. The aim of this study was to apply a public economic framework to a rare disease that takes into consideration a broad range of costs that are relevant to government in relation to transfers received and taxes paid. As a case study we constructed a simulation model to calculate the fiscal life course of an individual with hereditary transthyretin-mediated (hATTR) amyloidosis in The Netherlands. In this lethal disease different progressive disease scenarios occur, including polyneuropathy and/or cardiomyopathy. RESULTS: Due to progressive disability, health care resource use, and early death, hATTR amyloidosis with polyneuropathy receives more transfers from government compared to the general population. In a scenario where a patient is diagnoses with hATTR at age 45, an individual pays €180,812 less in lifetime taxes and receives incrementally €111,695 in transfers from the government, compared to a person without hATTR. Patients suffering from cardiomyopathy die after median 4 years. The health costs of this scenario are therefore lower than that of the other polyneuropathy-based scenarios. CONCLUSIONS: The fiscal analysis illustrates how health conditions influence not only health costs, but also the cross-sectorial public economic burden attributed to lost tax revenues and public disability allowances. Due to the progressive nature of hATTR amyloidosis used in this study, public costs including disability increase as the disease progresses with reduced lifetime taxes paid. The results indicate that halting disease progression early in the disease course would generate fiscal benefits beyond health benefits for patients. This analysis highlights the fiscal consequences of diseases and the need for broader perspectives applied to evaluate health conditions. Conventional cost-effectiveness framework used by many health technology assessment agencies have well-documented limitations in the field of rare diseases and fiscal modeling should be a complementary approach to consider.