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

BackgroundTwo 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.MethodsIn 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.Results387 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 (β: −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.ConclusionsTreatment 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.

Download Full-text

Agalsidase alfa and agalsidase beta in the treatment of Fabry disease: does the dose really matter?

Genetics in Medicine ◽

10.1038/gim.2014.79 ◽

2014 ◽

Vol 17 (1) ◽

pp. 21-23 ◽

Cited By ~ 3

Author(s):

Antonio Pisani ◽

Eleonora Riccio ◽

Massimo Sabbatini

Keyword(s):

Fabry Disease ◽

Agalsidase Beta ◽

Agalsidase Alfa

Download Full-text

Successful Management of Enzyme Replacement Therapy in Related Fabry Disease Patients with Severe Adverse Events by Switching from Agalsidase Beta (Fabrazyme®) to Agalsidase Alfa (Replagal®)

10.1007/8904_2014_304 ◽

2014 ◽

Cited By ~ 1

Author(s):

Kazuya Tsuboi ◽

Hiroshi Yamamoto ◽

Fuji Somura ◽

Hiromi Goto

Keyword(s):

Adverse Events ◽

Enzyme Replacement Therapy ◽

Fabry Disease ◽

Replacement Therapy ◽

Agalsidase Beta ◽

Successful Management ◽

Enzyme Replacement ◽

Agalsidase Alfa ◽

Severe Adverse Events

Download Full-text

Treatment switch in Fabry disease- a matter of dose?

Journal of Medical Genetics ◽

10.1136/jmedgenet-2020-106874 ◽

2020 ◽

pp. jmedgenet-2020-106874

Author(s):

Malte Lenders ◽

Peter Nordbeck ◽

Sima Canaan-Kühl ◽

Lukas Kreul ◽

Thomas Duning ◽

...

Keyword(s):

Fabry Disease ◽

Dose Group ◽

Clinical Symptoms ◽

Organ Damage ◽

Agalsidase Beta ◽

Disease Epidemiology ◽

Reduced Dose ◽

Clinical Events ◽

Agalsidase Alfa ◽

Switch Group

BackgroundPatients with Fabry disease (FD) on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in chronic kidney disease epidemiology collaboration-based estimated glomerular filtration rate (eGFR) and a worsened plasma lyso-Gb3 decrease. Hence, the most effective dose is still a matter of debate.MethodsIn this prospective observational study, we assessed end-organ damage and clinical symptoms in 78 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, which were assigned to continue this treatment (agalsidase-beta, regular-dose group, n=17); received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n=22); or were re-switched to agalsidase-beta after receiving agalsidase-alfa for 12 months (re-switch group, n=39) with a follow-up of 88±25 months.ResultsNo differences for clinical events were observed for all groups. Patients within the re-switch group started with the worst eGFR values at baseline (p=0.0217). Overall, eGFR values remained stable in the regular-dose group (p=0.1052) and decreased significantly in the re-switch and switch groups (p<0.0001 and p=0.0052, respectively). However, in all groups males presented with an annual loss of eGFR by –2.9, –2.5 and −3.9 mL/min/1.73 m² (regular-dose, re-switch, switch groups, all p<0.05). In females, eGFR decreased significantly only in the re-switch group by −2.9 mL/min/1.73 m² per year (p<0.01). Lyso-Gb3 decreased in the re-switch group after a change back to agalsidase-beta (p<0.05).ConclusionsOur data suggest that a re-switch to high dosage of agalsidase results in a better biochemical response, but not in a significant renal amelioration especially in classical males.

Download Full-text