Cost-effectiveness of Enzyme Replacement Therapy for Fabry Disease

Rombach, Saskia M.; Dijkgraaf, Marcel G. W.; Linthorst, Gabor E.; Hollak, Carla E. M.

doi:10.1016/j.ymgme.2011.11.141

Cited by 17 publications

(30 citation statements)

References 29 publications

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“…As Fabry disease is now being added to newborn screening panels in several locations, the number of identified patients is expected to increase greatly. Although α-Gal A replacement therapy has been available since the early 2000s (50,51), it is limited by its extreme cost and serious risk of deleterious immune reactions (52)(53)(54). Furthermore, enzyme replacement therapy is not effective in some patients, such as those with advanced end-stage organ disease and multiple comorbidities (55), and does not completely alleviate the neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Neuropathic pain in a Fabry disease rat model

et al. 2018

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Fabry disease, the most common lysosomal storage disease, affects multiple organs and results in a shortened life span. This disease is caused by a deficiency of the lysosomal enzyme α-galactosidase A, which leads to glycosphingolipid accumulation in many cell types. Neuropathic pain is an early and severely debilitating symptom in patients with Fabry disease, but the cellular and molecular mechanisms that cause the pain are unknown. We generated a rat model of Fabry disease, the first nonmouse model to our knowledge. Fabry rats had substantial serum and tissue accumulation of α-galactosyl glycosphingolipids and had pronounced mechanical pain behavior. Additionally, Fabry rat dorsal root ganglia displayed global N-glycan alterations, sensory neurons were laden with inclusions, and sensory neuron somata exhibited prominent sensitization to mechanical force. We found that the cation channel transient receptor potential ankyrin 1 (TRPA1) is sensitized in Fabry rat sensory neurons and that TRPA1 antagonism reversed the behavioral mechanical sensitization. This study points toward TRPA1 as a potentially novel target to treat the pain experienced by patients with Fabry disease.

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Section: Discussionmentioning

confidence: 99%

Neuropathic pain in a Fabry disease rat model

et al. 2018

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“…In addition, some patients developed immune responses to the infused recombinant enzymes (Lidove et al, ). The typically short half‐life of enzymes and the need for repeated administration of large amounts of enzyme make ERT extremely expensive (an estimated US$200,000 per patient per year in 2012) (Rombach, Hollak, Linthorst, & Dijkgraaf, ). Therefore, other treatments are still needed for better management of Fabry disease.…”

Section: Biologicsmentioning

confidence: 99%

Drug discovery and development for rare genetic disorders

Sun

Zheng

Simeonov

2017

American J of Med Genetics Pt A

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Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed. Rare diseases are usually genetic diseases; hence, employing pharmacogenetics to develop treatments and using whole genome sequencing to identify the etiologies for such diseases are appropriate strategies to exploit. Beginning with high throughput screening of small molecules, the benefits and challenges of target-based and phenotypic screens are discussed. Explanations and examples of drug repurposing are given; drug repurposing as an approach to quickly move programs to clinical trials is evaluated. Consideration is given to the category of biologics which include gene therapy, recombinant proteins, and autologous transplants. Disease models, including animal models and induced pluripotent stem cells (iPSCs) derived from patients, are surveyed. Finally, the role of biomarkers in drug discovery and development, as well as clinical trials, is elucidated.

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“…Fabry erbrachten akzeptable Zusatzkosten pro qualitätsadjustiertes Lebensjahr (QALY) [23,28], für M. Pompe gilt dies wohl nur für bestimmte Subpopulationen [19].…”

Section: öKonomische Und Rechtliche Aspekte Der Ertunclassified

Lysosomale Speichererkrankungen: Herausforderungen bei der sektorübergreifenden, multiprofessionellen Patientenversorgung mit Enzymersatztherapie

Lagler¹,

Beck

Scarpa

et al. 2017

Klin Padiatr

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Due to their rarity studies in (ultra-) rare diseases are difficult. Only for a minority of these diseases causal therapies are available. Development and production of enzyme replacement therapies (ERT) for example are challenging and expensive. The number of patients is low, costs per patient are high. We will focus on the challenges of providing long-term ERT to patients with lysosomal storage diseases (LSD) in an out- and inpatient setting based on a literature search in Pubmed and own experience. Many ERTs for LSDs have a positive cost-benefit ratio. Possible side-effects are severe allergic reactions. ERT is covered by the insurance companies when prescribed by a physician, however they are liable to recourse by the insurance company as the expenses for drugs of the prescribing physician will be above average. In most cases the recourse can be averted if diagnoses of individual patients are disclosed. Intravenous infusion of ERT is not well-regulated in Germany/Austria. Infusion on a ward is safe however often not covered by the insurance companies as patients do not stay overnight. Another option is infusion in a day-care setting, however the lump sum paid for infusion does not cover costs for ERT. On an individual basis, reimbursement for medication (ERT) has to be negotiated with the insurance companies before infusion takes place. Home infusions are feasible, however careful evaluations of the infusion-team and the risk for side-effects have to be performed on an individual basis, legal issues have to be considered. In- and outpatient ERT of patients with LSDs is challenging but feasible after individual evaluation of patient and infusion team.

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Cost-effectiveness of Enzyme Replacement Therapy for Fabry Disease

Abstract: Background: The cost-effectiveness of enzyme replacement therapy (ERT) compared to standard medical care was evaluated in the Dutch cohort of patients with Fabry disease.

Cited by 17 publications

References 29 publications

Neuropathic pain in a Fabry disease rat model

Neuropathic pain in a Fabry disease rat model

Drug discovery and development for rare genetic disorders

Lysosomale Speichererkrankungen: Herausforderungen bei der sektorübergreifenden, multiprofessionellen Patientenversorgung mit Enzymersatztherapie

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