Enzyme replacement therapy interruption in patients with Mucopolysaccharidoses: Recommendations for distinct scenarios in Latin America

Solano, Martha; Fainboim, Alejandro; Politei, Juan; Porras-Hurtado, Gloria Liliana; Martins, Ana María; Souza, Carolina Guerini de; Koch, Felipe Mendez; Amartino, Hernán; Satizábal, José María; Horovitz, Dafne Dain Gandelman; Medeiros, Paula Frassinetti Vasconcelos de; Honjo, Rachel Sayuri; Lourenço, Charles Marques

doi:10.1016/j.ymgmr.2020.100572

Cited by 13 publications

(10 citation statements)

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“…The impossibility of some physicians to assess patients' response to anesthetic procedures in most cases, as well as carpal tunnel syndrome and hepatosplenomegaly after ERT interruption may be regarded as a limitation of this current report. Earlier this year, Latin American specialists have established and published important recommendations for managing ERT interruptions, and proposed key parameters for patients' follow‐up to better comprehend the effects of treatment discontinuation, 10 which could improve future analyses and enable more detailed insights.…”

Section: Discussionmentioning

confidence: 99%

“…The effects of short and long‐term ERT interruptions on MPS IVA patients have not been thoroughly investigated, although temporary treatment interruption occur at high frequencies in many low and middle‐income countries due to drug supply/logistics, reimbursement issues and difficulty in obtaining high‐cost treatment from the health system 10 . Studies on other types of MPS have shown that ERT interruption may reverse its beneficial effects and, in some cases, even worsen clinical outcomes; most striking is the fact that resuming ERT after a period of interruption is not able to fully reverse the effects of treatment discontinuation 11,12 .…”

Section: Introductionmentioning

confidence: 99%

“…6 The effects of short and long-term ERT interruptions on MPS IVA patients have not been thoroughly investigated, although temporary treatment interruption occur at high frequencies in many low and middle-income countries due to drug supply/logistics, reimbursement issues and difficulty in obtaining highcost treatment from the health system. 10 Studies on other types of MPS have shown that ERT interruption may reverse its beneficial effects and, in some cases, even worsen clinical outcomes; most striking is the fact that resuming ERT after a period of interruption is not able to fully reverse the effects of treatment discontinuation. 11,12 The mechanisms by which ERT interruption causes worsening of some clinical outcomes are still unclear; however, it has been hypothesized that GAGs metabolism and inhibition of residual enzyme activity, genetically and epigenetically regulated, may play important roles in the disease rebound effect after ERT reintroduction.…”

Section: Introductionmentioning

confidence: 99%

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Enzyme replacement therapy interruption in mucopolysaccharidosis type IVA patients and its impact in different clinical outcomes

et al. 2021

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Mucopolysaccharidosis type IVA (MPS IVA) is an autosomal recessive lysosomal storage disorder caused by mutations in the GALNS gene, which leads to deficient activity of N‐acetylglucosamine‐6‐sulfate sulfatase. MPS IVA patients usually present skeletal dysplasia, coarse features, short stature, airway obstruction, cervical spinal cord compression, dental abnormalities, and cardiac valvular alterations. Enzyme replacement therapy (ERT) with elosulfase alfa is the only disease‐specific treatment available for MPS IVA patients and has been shown to improve important clinical and biochemical parameters; however, little is known about the effects of ERT interruption on these patients. In this article, we report the impact of different periods of treatment interruption on clinical outcomes of 18 MPS IVA patients. All MPS IVA patients included in this case series were treated and followed up in Latin American centers and had been receiving elosulfase alfa intravenously for at least 8 months before ERT was interrupted. Different clinical parameters and assessments were evaluated at variable timepoints following therapy interruption. Altogether, our report indicates that some beneficial ERT effects in MPS IVA patients may last after different periods of treatment interruption, as cardiac and respiratory function improvements. However, worsening of important disease parameters after ERT interruption, such as the increase in uGAGs, pain, joint and skeletal aspects, and surgery indications suggests that treatment discontinuation should be avoided in order to maintain the disease as stable as possible, aiming to optimize these patients' life expectancy and quality of life.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enzyme replacement therapy interruption in mucopolysaccharidosis type IVA patients and its impact in different clinical outcomes

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“…The economical problems related to high cost of enzyme replacement therapy (several hundred thousand dollars/euros per year; the exact price depends on patient’s body weight as the enzyme dose is given per kg), including problems with reimbursement of the costs, have been recognized earlier (Schlander and Beck 2009 ). In fact, interruption of this kind of therapy because of refusal of covering costs by insurance companies or governmental health agencies became a real problem in many countries (Solano et al 2020 ). Precise economic analyses were performed for enzyme replacement therapy in a couple of diseases.…”

Section: Introductionmentioning

confidence: 99%

One drug to treat many diseases: unlocking the economic trap of rare diseases

2020

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There are two major problems with the development of therapies for rare diseases. First, among over 7000 such diseases, the vast majority are caused by genetic defects and/or include neurodegeneration, making them very difficult to treat. Second, drugs for rare diseases, so-called orphan drugs, are extremely expensive, as only a small number of patients are interested in purchasing them. This results in the appearance of a specific economic trap of rare diseases; namely, despite high biomedical, pharmaceutical and technological potential, the development of new orphan drugs is blocked by the economic reality. The purpose of this work was to find a potential solution that might resolve this economic trap of rare diseases. A literature review was conducted, and a hypothesis was formulated assuming that the use of one drug for the treatment of many rare diseases might overcome the economic trap. We provide examples showing that finding such drugs is possible. Thus, a possible solution for the problem of developing orphan drugs is presented. Further preclinical and clinical studies, although neither easy nor inexpensive, should verify whether the hypothesis regarding the possibility of unlocking the economic trap of rare diseases is valid.

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“…They concluded that skeletal manifestations did not resolve after treatment reinstatement. In MPS, ERT interruption can lead to the loss of the beneficial effects and, in some circumstances, the abrupt withdrawal of ERT significantly worsened the clinical evolution of the patient, especially if the interruptions were for more than two months [28][29][30][31].…”

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confidence: 99%

Fabry disease during the COVID-19 pandemic. Why and how treatment should be continued

Politei¹

2020

Molecular Genetics and Metabolism

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Fabry disease is an X-linked disease due to a deficiency of the lysosomal enzyme alpha-galactosidase A. Clinical symptoms in classically affected males include acroparesthesia, anhydrosis and angiokeratoma, which may present during childhood followed by cardiac, cerebral and renal complications. Even though pulmonary involvement is not widely appreciated by clinicians, an obstructive lung disease is another recognized component of Fabry disease. Coronavirus Disease-19 (COVID-19), caused by the SARS-CoV-2 virus was labeled as a global pandemic and patients with Fabry disease can be considered at high risk of developing severe complications. The impact of COVID-19 on patients with Fabry disease receiving enzyme replacement therapy is still unknown. Many patients who receive treatment in the hospital experienced infusion disruptions due to fear of infection. Effects of temporary treatment interruption was described in more detail in other lysosomal storage diseases, but the recommencement of therapy does not fully reverse clinical decline due to the temporary discontinuation. When possible, home-therapy seems to be the most efficient way to maintain enzyme replacement therapy access during pandemic. Sentence take-home message: Home-therapy, when possible, seems to be the most efficient way to maintain enzyme replacement therapy access during pandemic in patients with Fabry disease.

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Enzyme replacement therapy interruption in patients with Mucopolysaccharidoses: Recommendations for distinct scenarios in Latin America

Cited by 13 publications

References 50 publications

Enzyme replacement therapy interruption in mucopolysaccharidosis type IVA patients and its impact in different clinical outcomes

Enzyme replacement therapy interruption in mucopolysaccharidosis type IVA patients and its impact in different clinical outcomes

One drug to treat many diseases: unlocking the economic trap of rare diseases

Fabry disease during the COVID-19 pandemic. Why and how treatment should be continued

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