Treatment of fabry disease with migalastat-outcome from a prospective 24 months observational multicenter study (FAMOUS)
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Treatment of fabry disease with migalastat-outcome from a prospective 24 months observational multicenter study (FAMOUS). / Lenders, Malte; Nordbeck, Peter; Kurschat, Christine; Eveslage, Maria; Karabul, Nesrin; Kaufeld, Jessica; Hennermann, Julia B; Patten, Monica; Cybulla, Markus; Müntze, Jonas; Üçeyler, Nurcan; Liu, Dan; Das, Anibh M; Sommer, Claudia; Pogoda, Christian; Reiermann, Stefanie; Duning, Thomas; Gaedeke, Jens; von Cossel, Katharina; Blaschke, Daniela; Brand, Stefan-Martin; Alexander Mann, W; Kampmann, Christoph; Muschol, Nicole; Canaan-Kühl, Sima; Brand, Eva.
In: EUR HEART J-CARD PHA, Vol. 8, No. 3, 05.2022, p. 272–281.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Treatment of fabry disease with migalastat-outcome from a prospective 24 months observational multicenter study (FAMOUS)
AU - Lenders, Malte
AU - Nordbeck, Peter
AU - Kurschat, Christine
AU - Eveslage, Maria
AU - Karabul, Nesrin
AU - Kaufeld, Jessica
AU - Hennermann, Julia B
AU - Patten, Monica
AU - Cybulla, Markus
AU - Müntze, Jonas
AU - Üçeyler, Nurcan
AU - Liu, Dan
AU - Das, Anibh M
AU - Sommer, Claudia
AU - Pogoda, Christian
AU - Reiermann, Stefanie
AU - Duning, Thomas
AU - Gaedeke, Jens
AU - von Cossel, Katharina
AU - Blaschke, Daniela
AU - Brand, Stefan-Martin
AU - Alexander Mann, W
AU - Kampmann, Christoph
AU - Muschol, Nicole
AU - Canaan-Kühl, Sima
AU - Brand, Eva
N1 - © Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2021. For permissions, please email: journals.permissions@oup.com.
PY - 2022/5
Y1 - 2022/5
N2 - AIMS: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (GLA/AGAL) resulting in lysosomal accumulation of globotriaosylceramide (Gb3). Patients with amenable GLA mutations can be treated with migalastat, an oral pharmacologic chaperone increasing endogenous AGAL activity. In this prospective observational multicenter study safety as well as cardiovascular, renal, and patient-reported outcomes and disease biomarkers were assessed after 12 and 24 months of migalastat treatment under "real world" conditions.METHODS AND RESULTS: 54 patients (26 females) (33 of these [61.1%] pre-treated with enzyme replacement therapy) with amenable mutations were analyzed. Treatment was generally safe and well tolerated. 153 events per 1,000 patient-years were detected. Overall left ventricular mass index decreased after 24 months (all: -7.5 ± 17.4 g/m2, p = 0.0118; females: -4.6 ± 9.1 g/m2, p = 0.0554; males: -9.9 ± 22.2 g/m2, p = 0.0699). After 24 months, females and males presented with a moderate yearly loss of eGFR (-2.6 and -4.4 ml/min/1.73 m2 per year; p = 0.0317 and p = 0.0028, respectively). FD-specific manifestations/symptoms remained stable (all p > 0.05). 76.9% of females and 50% of males suffered from pain, which has not improved under treatment. FD-specific disease scores (DS3 and MSSI) remained stable during treatment. AGAL activities and plasma lyso-Gb3 values remained stable, although some male patients presented with increasing lyso-Gb3 levels over time.CONCLUSIONS: Treatment with migalastat was generally safe and resulted in most patients in an amelioration of left ventricular mass. However, due to the heterogeneity of FD phenotypes, it is advisable that the treating physician monitors the clinical response regularly.
AB - AIMS: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (GLA/AGAL) resulting in lysosomal accumulation of globotriaosylceramide (Gb3). Patients with amenable GLA mutations can be treated with migalastat, an oral pharmacologic chaperone increasing endogenous AGAL activity. In this prospective observational multicenter study safety as well as cardiovascular, renal, and patient-reported outcomes and disease biomarkers were assessed after 12 and 24 months of migalastat treatment under "real world" conditions.METHODS AND RESULTS: 54 patients (26 females) (33 of these [61.1%] pre-treated with enzyme replacement therapy) with amenable mutations were analyzed. Treatment was generally safe and well tolerated. 153 events per 1,000 patient-years were detected. Overall left ventricular mass index decreased after 24 months (all: -7.5 ± 17.4 g/m2, p = 0.0118; females: -4.6 ± 9.1 g/m2, p = 0.0554; males: -9.9 ± 22.2 g/m2, p = 0.0699). After 24 months, females and males presented with a moderate yearly loss of eGFR (-2.6 and -4.4 ml/min/1.73 m2 per year; p = 0.0317 and p = 0.0028, respectively). FD-specific manifestations/symptoms remained stable (all p > 0.05). 76.9% of females and 50% of males suffered from pain, which has not improved under treatment. FD-specific disease scores (DS3 and MSSI) remained stable during treatment. AGAL activities and plasma lyso-Gb3 values remained stable, although some male patients presented with increasing lyso-Gb3 levels over time.CONCLUSIONS: Treatment with migalastat was generally safe and resulted in most patients in an amelioration of left ventricular mass. However, due to the heterogeneity of FD phenotypes, it is advisable that the treating physician monitors the clinical response regularly.
U2 - 10.1093/ehjcvp/pvab025
DO - 10.1093/ehjcvp/pvab025
M3 - SCORING: Journal article
C2 - 33725118
VL - 8
SP - 272
EP - 281
JO - EUR HEART J-CARD PHA
JF - EUR HEART J-CARD PHA
SN - 2055-6837
IS - 3
ER -
