Two decades of experience of the Fabry Outcome Survey provides further confirmation of the long-term effectiveness of agalsidase alfa enzyme replacement therapy

Abstract

Agalsidase alfa; Fabry disease; Registry data

Agalsidasa alfa; Enfermedad de Fabry; Datos de registro

Agalsidasa alfa; Malaltia de Fabry; Dades de registre

Background Analyses of up to 20 years of data from the Fabry Outcome Survey (FOS) assessed the long-term effectiveness of agalsidase alfa enzyme replacement therapy. Methods The impact of agalsidase alfa treatment on renal, cardiac, morbidity, and mortality outcomes in FOS was compared with untreated external Fabry disease (FD) cohorts. Results A total of 2171 FOS patients (1014 men, 919 women, 163 boys, 75 girls) received agalsidase alfa (median [range] duration of treatment: 5.38 [0.0–20.8] years). Annual rates of decline in estimated glomerular filtration rate improved in treated patients versus untreated external cohorts regardless of sex or baseline urinary protein levels. Annual left ventricular mass index rates were stable in treated patients regardless of sex or baseline left ventricular hypertrophy status, and better than in untreated external cohorts. The mean age at which 50 % of patients had their first composite morbidity event was later in the agalsidase-alfa-treated population than in the untreated external cohort (51.7 vs 41 years [males]; 60.8 vs 53 years [females]). After 24 months of treatment, the probability of a composite morbidity event was ∼34 % in treated patients and ∼ 45 % in untreated patients. Treated patients were older at death than untreated patients (mean [range]: 61.7 [26.2–87.6] vs 50.3 [34.5–70.1] years). The mean age at which 50 % of male patients were still alive was higher in treated patients than in untreated external cohorts (75.5 vs 60.0 years). Conclusions Long-term treatment with agalsidase alfa may provide renal, cardiac, and overall survival protection in FD.

FOS and this analysis were funded by Takeda Pharmaceuticals International AG, which also assisted in analyzing the data and preparing the manuscript. Under the direction of the authors, medical writing support was provided by Ester Baixauli PhD of Oxford PharmaGenesis and funded by Takeda Development Center Americas, Inc. The final decision to submit the manuscript for publication was made by the authors.