Long-term multisystemic efficacy of migalastat on Fabry-associated clinical events, including renal, cardiac and cerebrovascular outcomes
Por:
Hughes, DA, Bichet, DG, Giugliani, R, Hopkin, RJ, Krusinska, E, Nicholls, K, Olivotto, I, Feldt-Rasmussen, U, Sakai, N, Skuban, N, Sunder-Plassmann, G, Torra, R, Wilcox, WR
Publicada:
1 jul 2023
Ahead of Print:
1 dic 2022
Resumen:
Background Fabry disease is a rare, multisystemic disorder caused by GLA gene variants that lead to alpha galactosidase A deficiency, resulting in accumulation of glycosphingolipids and cellular dysfunction. Fabry-associated clinical events (FACEs) cause significant morbidity and mortality, yet the long-term effect of Fabry therapies on FACE incidence remains unclear.
Methods This posthoc analysis evaluated incidence of FACEs (as a composite outcome and separately for renal, cardiac and cerebrovascular events) in 97 enzyme replacement therapy (ERT)-naive and ERT-experienced adults with Fabry disease and amenable GLA variants who were treated with migalastat for up to 8.6 years (median: 5 years) in Phase III clinical trials of migalastat. Associations between baseline characteristics and incidence of FACEs were also evaluated.
Results During long-term migalastat treatment, 17 patients (17.5%) experienced 22 FACEs and there were no deaths. The incidence rate of FACEs was 48.3 events per 1000 patient-years overall. Numerically higher incidence rates were observed in men versus women, patients aged >40 years versus younger patients, ERT-naive versus ERT-experienced patients and men with the classic phenotype versus men and women with all other phenotypes. There was no statistically significant difference in time to first FACE when analysed by patient sex, phenotype, prior treatment status or age. Lower baseline estimated glomerular filtration rate (eGFR) was associated with an increased risk of FACEs across patient populations.
Conclusions The overall incidence of FACEs for patients during long-term treatment with migalastat compared favourably with historic reports involving ERT. Lower baseline eGFR was a significant predictor of FACEs.
Filiaciones:
Hughes, DA:
Royal Free London NHS Fdn Trust, Lysosomal Storage Disorders Unit, London NW3 2QG, England
UCL, London NW3 2QG, England
Bichet, DG:
Univ Montreal, Hop Sacre Coeur, Montreal, PQ, Canada
Giugliani, R:
Univ Fed Rio Grande do Sul, Dept Genet, Med Genet Serv, HCPA,DASA, Porto Alegre, Brazil
INAGEMP, Porto Alegre, Brazil
Hopkin, RJ:
Cincinnati Childrens Hosp, Div Human Genet, Coll Med, Dept Pediat, Cincinnati, OH USA
Univ Cincinnati, Cincinnati, OH USA
Krusinska, E:
Amicus Therapeut Inc, Clin Dev, Philadelphia, PA USA
Nicholls, K:
Univ Melbourne, Royal Melbourne Hosp, Dept Nephrol, Parkville, Vic, Australia
Olivotto, I:
Med Univ Vienna, Dept Med 3, Div Nephrol & Dialysis, Florence, Austria
Feldt-Rasmussen, U:
Univ Autonoma Barcelona, Natl Univ Hosp, Dept Med Endocrinol & Metab, Rigshosp, Barcelona, Spain
Sakai, N:
Emory Univ, Dept Human Genet, Grad Sch Med, Atlanta, GA USA
Skuban, N:
Amicus Therapeut Inc, Clin Dev, Philadelphia, PA USA
Green Published, hybrid, All Open Access, Hybrid Gold, Green
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