Dataset Information

Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study.

ABSTRACT: BACKGROUND:Two recombinant enzymes (agalsidase alfa 0.2?mg/kg/every other week and agalsidase beta 1.0?mg/kg/every other week) have been registered for the treatment of Fabry disease (FD), at equal high costs. An independent international initiative compared clinical and biochemical outcomes of the two enzymes. METHODS:In this multicentre retrospective cohort study, clinical event rate, left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), antibody formation and globotriaosylsphingosine (lysoGb3) levels were compared between patients with FD treated with agalsidase alfa and beta at their registered dose after correction for phenotype and sex. RESULTS:387 patients (192 women) were included, 248 patients received agalsidase alfa. Mean age at start of enzyme replacement therapy was 46 (±15) years. Propensity score matched analysis revealed a similar event rate for both enzymes (HR 0.96, P=0.87). The decrease in plasma lysoGb3 was more robust following treatment with agalsidase beta, specifically in men with classical FD (?: -18?nmol/L, P<0.001), persisting in the presence of antibodies. The risk to develop antibodies was higher for patients treated with agalsidase beta (OR 2.8, P=0.04). LVMI decreased in a higher proportion following the first year of agalsidase beta treatment (OR 2.27, P=0.03), while eGFR slopes were similar. CONCLUSIONS:Treatment with agalsidase beta at higher dose compared with agalsidase alfa does not result in a difference in clinical events, which occurred especially in those with more advanced disease. A greater biochemical response, also in the presence of antibodies, and better reduction in left ventricular mass was observed with agalsidase beta.

SUBMITTER: Arends M

PROVIDER: S-EPMC5931248 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study.

Arends Maarten M Biegstraaten Marieke M Wanner Christoph C Sirrs Sandra S Mehta Atul A Elliott Perry M PM Oder Daniel D Watkinson Oliver T OT Bichet Daniel G DG Khan Aneal A Iwanochko Mark M Vaz Frédéric M FM van Kuilenburg André B P ABP West Michael L ML Hughes Derralynn A DA Hollak Carla E M CEM

Journal of medical genetics 20180207 5

<h4>Background</h4>Two recombinant enzymes (agalsidase alfa 0.2 mg/kg/every other week and agalsidase beta 1.0 mg/kg/every other week) have been registered for the treatment of Fabry disease (FD), at equal high costs. An independent international initiative compared clinical and biochemical outcomes of the two enzymes.<h4>Methods</h4>In this multicentre retrospective cohort study, clinical event rate, left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), antibody forma ...[more]

PMID: 29437868

Similar Datasets

Project description:Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ~ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m(2) had a mean (standard error of the mean [SEM]) annualized change in eGFR of - 2.86 (0.53) mL/min/1.73 m(2)/y compared with - 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m(2.7)/y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ~ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ~ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take into account that they are based on retrospective comparisons with previously published data.

Dataset Information

Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study.

Publications

Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets