Long-term outcomes with agalsidase alfa enzyme replacement therapy: Analysis using deconstructed composite events

Abstract

A B S T R A C TThis is a retrospective analysis of Fabry Outcome Survey data from children/adults (n = 677) receiving agalsidase alfa enzyme replacement therapy for a median of 3 years, examining cerebrovascular, cardiac, and renal morbidity endpoints separately. Cardiac events occurred at younger ages than cerebrovascular or renal events, cerebrovascular events were more frequent in females than males, and males were more likely to experience cardiac and renal events at a younger age than females.

Clinical and economic impact of screening for Fabry disease in children from high risk groups

“…Вероятность наступления комбинированной конечной точки, включающей гемодиализ, трансплантацию почки либо увеличение уровня креатинина более чем на 33% от базового значения, рассчитывали на основании кривой Каплана-Майера, построенной согласно методике, описанной в работе M. Beck и соавт. [41] и адаптированной для популяции российских пациентов. Расчетное количество осложнений у пациентов с БФ, которым в детстве было установлено любое "маскирующее" заболевание, для мужчин составило 55 событий в год, для женщин -12 событий.…”

Lysosomal Leukodystrophies Lysosomal Storage Diseases Associated With White Matter Abnormalities

“…66 However, enzyme replacement therapy is unable to alter the risk of stroke and/or improve the "white matter lesions" or hyperintensities observed in brain MRI. [67][68][69] More recently, in a large cohort of patients with Fabry disease, no association between enzyme replacement therapy and white matter hyperintensity (WMH) progression was noted, whereas higher total cholesterol at baseline was associated with slower WMH progression, suggesting a complex and still unclear relationship between cholesterol, lowering cholesterol drugs (statins), and cerebral small vessel disease in Fabry disease. 70 In terms of peripheral neuropathy, enzyme replacement therapy may improve proximal skin innervation in patients with good renal function, but does not protect small fiber function in men with impaired renal function.…”

Fabry Disease

“…La presencia de mayor cantidad de residuos de manosa 6 -fosfato produce un mejor reconocimiento por los receptores de manosa 6 -fosfato de la membrana celular y consecuentemente mayor internalización celular de la enzima 9,66 . De acuerdo con los estudios publicados, pareciera que el beneficio tisular y clínico tiene relación directa con la dosis de TRE utilizada 9,[67][68][69][70][71][72] . Distintos protocolos han demostrado que el uso de agalsidasa beta a dosis de 1mg/kg cada 14 días produce remoción total de Gb3 de los podocitos renales en comparación con la agalsidasa alfa a dosis de 0,2mg/kg9,70-72.…”