Long-term multisystemic efficacy of migalastat on Fabry-associated clinical events, including renal, cardiac and cerebrovascular outcomes
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Long-term multisystemic efficacy of migalastat on Fabry-associated clinical events, including renal, cardiac and cerebrovascular outcomes. / Hughes, Derralynn A; Bichet, Daniel G; Giugliani, Roberto; Hopkin, Robert J; Krusinska, Eva; Nicholls, Kathleen; Olivotto, Iacopo; Feldt-Rasmussen, Ulla; Sakai, Norio; Skuban, Nina; Sunder-Plassmann, Gere; Torra, Roser; Wilcox, William R.
I: Journal of Medical Genetics, Bind 60, Nr. 7, 2023, s. 722-731.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Long-term multisystemic efficacy of migalastat on Fabry-associated clinical events, including renal, cardiac and cerebrovascular outcomes
AU - Hughes, Derralynn A
AU - Bichet, Daniel G
AU - Giugliani, Roberto
AU - Hopkin, Robert J
AU - Krusinska, Eva
AU - Nicholls, Kathleen
AU - Olivotto, Iacopo
AU - Feldt-Rasmussen, Ulla
AU - Sakai, Norio
AU - Skuban, Nina
AU - Sunder-Plassmann, Gere
AU - Torra, Roser
AU - Wilcox, William R
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Cardiovascular Diseases
KW - Cerebrovascular Disorders
KW - Mutation
KW - Genetics
KW - Medical
KW - ENZYME REPLACEMENT THERAPY
KW - AGALSIDASE-BETA
KW - DISEASE
KW - DEATH
KW - LIFE
U2 - 10.1136/jmg-2022-108669
DO - 10.1136/jmg-2022-108669
M3 - Journal article
C2 - 36543533
VL - 60
SP - 722
EP - 731
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
SN - 0022-2593
IS - 7
ER -
ID: 345315592