Clinical relevance of endpoints in clinical trials for acid sphingomyelinase deficiency enzyme replacement therapy.
Mol Genet Metab
; 131(1-2): 116-123, 2020.
Article
em En
| MEDLINE
| ID: mdl-32616389
ABSTRACT
BACKGROUND:
Acid sphingomyelinase deficiency (ASMD) also known as Niemann-Pick disease, is a rare lysosomal storage disorder with a diverse disease spectrum that includes slowly progressive, chronic visceral (type B) and neurovisceral forms (intermediate type A/B), in addition to infantile, rapidly progressive fatal neurovisceral disease (type A). PURPOSE ANDMETHODS:
We review the published evidence on the relevance of splenomegaly and reduced lung diffusion capacity to the clinical burden of chronic forms of ASMD. Targeted literature searches were conducted to identify relevant ASMD and non-ASMD studies for associations between diffusing capacity of the lungs for carbon monoxide (DLCO) and splenomegaly, with clinical parameters and outcome measures.RESULTS:
Respiratory disease and organomegaly are primary and independent contributors to mortality, disease burden, and morbidity for patients with chronic ASMD. The degree of splenomegaly correlates with short stature, atherogenic lipid profile, and degree of abnormality of hematologic parameters, and thus may be considered a surrogate marker for bleeding risk, abnormal lipid profiles and possibly, liver fibrosis. Progressive lung disease is a prevalent clinical feature of chronic ASMD, contributing to a decreased quality of life (QoL) and an increased disease burden. In addition, respiratory-related complications are a major cause of mortality in ASMD.CONCLUSIONS:
The reviewed evidence from ASMD natural history and observational studies supports the use of lung function and spleen volume as clinically meaningful endpoints in ASMD trials that translate into important measures of disease burden for patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
6_ODS3_enfermedades_notrasmisibles
/
7_ODS3_muertes_prevenibles_nacidos_ninos
Base de dados:
MEDLINE
Assunto principal:
Esfingomielina Fosfodiesterase
/
Esplenomegalia
/
Doenças de Niemann-Pick
/
Doenças por Armazenamento dos Lisossomos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Aspecto:
Patient_preference
Limite:
Humans
Idioma:
En
Revista:
Mol Genet Metab
Ano de publicação:
2020
Tipo de documento:
Article