Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F19%3A10399836" target="_blank" >RIV/00064165:_____/19:10399836 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/19:10399836

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=jqgRudc1a6" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=jqgRudc1a6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ymgme.2019.03.010" target="_blank" >10.1016/j.ymgme.2019.03.010</a>

Result language

angličtina

Original language name

Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial

Original language description

Background: Fabry disease is a rare, X-linked, lifelong progressive lysosomal storage disorder. Severely deficient a-galactosidase A activity in males is associated with the classic phenotype with early-onset, multisystem manifestations evolving to vital organ complications during adulthood. We assessed the ability of 2 low-dose agalsidase beta regimens to lower skin, plasma, and urine globotriaosylceramide (GL-3) levels, and influence clinical manifestations in male pediatric Fabry patients. Methods: In this multicenter, open-label, parallel-group, phase 3b study, male patients aged 5-18 years were randomized to receive agalsidase beta at 0.5 mg/kg 2-weekly (n = 16) or 1.0 mg/kg 4-weekly (n = 15) for 5 years. All had plasma/urine GL-3 accumulation but no clinically evident organ involvement. The primary outcome was GL-3 accumulation in superficial skin capillary endothelium (SSCE). Results: The mean age was 11.6 (range: 5-18) years and all but one of the 31 patients had classic GLA mutations. In the overall cohort, shifts from non-0 to 0-scores for SSCE GL-3 were significant at years 1, 3, and 5, but results were variable. Plasma GL-3 normalized and urine GL-3 reduced substantially. Higher anti-agalsidase beta antibody titers were associated with less robust SSCE GL-3 clearance and higher urine GL-3 levels. Renal function remained stable and normal. Most Fabry signs and symptoms tended to stabilize; abdominal pain was significantly reduced (-26.3%; P = .0215). No new clinical major organ complications were observed. GL-3 accumulation and cellular and vascular injury were present in baseline kidney biopsies (n = 7). Treatment effects on podocyte GL-3 content and foot process width were highly variable. Fabry arteriopathy overall increased in severity. Two patients withdrew and 2 had their agalsidase beta dose increased. Conclusions: Our findings increase the limited amount of available data on long-term effects of enzyme replacement therapy in pediatric, classic Fabry patients. The low-dose regimens studied here over a period of 5 years did not demonstrate a consistent benefit among the patients in terms of controlling symptomatology, urine GL-3 levels, and pathological histology. The current available evidence supports treatment of pediatric, classic male Fabry patients at the approved agalsidase beta dose of 1.0 mg/kg 2-weekly if these patients are considered for enzyme replacement therapy with agalsidase beta.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30201 - Cardiac and Cardiovascular systems

Project

—

Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecular Genetics and Metabolism

ISSN

1096-7192

e-ISSN

—

Volume of the periodical

127

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

9

Pages from-to

86-94

UT code for WoS article

000471735400011

EID of the result in the Scopus database

2-s2.0-85064183980