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.

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No association between increased prolactin levels and progression of left ventricular mass in German cohort study

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0028-1096371 ◽

2008 ◽

Vol 116 (09) ◽

Author(s):

A Steveling ◽

R Haring ◽

SB Felix ◽

M Nauck ◽

M Dörr ◽

...

Keyword(s):

Cohort Study ◽

Left Ventricular Mass ◽

Left Ventricular ◽

Ventricular Mass

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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

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P0067PREDICTORS OF LONG-TERM OUTCOME IN A SPANISH COHORT OF PATIENTS WITH FABRY DISEASE ON ENZYME REPLACEMENT THERAPY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0067 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Marian Goicoechea ◽

Francisco Gomez-Preciado ◽

Silvia Benito ◽

Joan Torras ◽

Roser Torra ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Fabry Disease ◽

Replacement Therapy ◽

Left Ventricular ◽

Response To Therapy ◽

Clinical Event ◽

Enzyme Replacement ◽

Clinical Events ◽

The Impact

Abstract Background and Aims Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in Fabry disease patients on ERT. Method Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). Results In 69 patients (42 males, 27 females, mean age 44.6 ±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242 to 128 mg/g (p = 0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR ≤60 ml/min/1.73 m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043), being these differences more relevant in females (log Rank 18.514, p<0.001) than males (logRank: 3.442, p=0.064). Lower baseline eGFR was associated with a 3- to 7-fold increase in the risk of clinical events in different Cox models. Conclusion GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes. For the first time, we show that initiation of ERT in women before renal function deteriorates has a similar or even larger impact as in Fabry males to prevent clinical events.

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