Prompt Agalsidase Alfa Therapy Initiation is Associated with Improved Renal and Cardiovascular Outcomes in a Fabry Outcome Survey Analysis

Drug Des Devel Ther 2021 Aug 16;15:3561-3572. doi: 10.2147/DDDT.S313789.

PMID: 34429585

Derralynn Hughes, Aleš Linhart, Andrey Gurevich

Highlights: This analysis suggests that prompt treatment initiation with agalsidase alfa provided better renal and cardiovascular outcomes than delayed treatment in patients with Fabry disease.

Abstract

Background: In patients with Fabry disease, the timing of enzyme replacement therapy initiation is thought to be crucial. The Fabry Outcome Survey data were used to analyze the impact of early versus late beginning of agalsidase alfa medication on cardiovascular and renal outcomes in patients with Fabry disease.

Methods: Patients having mutations linked with classical versus late-onset Fabry disease were defined using available genetic data at baseline. Patients in the prompt and delayed groups were compared in terms of time to cardiovascular or renal events from the start of treatment to 120 months. "Prompt" was defined as treatment initiation <24 months from symptom onset (analysis A) or diagnosis (analysis B), and "delayed" was defined as ≥24 months from symptom onset (analysis A) or diagnosis (analysis B). Event-free probability and time to first event were compared using Kaplan-Meier curves and Log rank testing. The hazard ratios were calculated using multivariate Cox regression (HRs).

Results: Thirteen hundred and seventy-four patients were studied based on the length of time since the onset of symptoms (172 prompt, 1202 delayed). In a multivariate Cox regression analysis, prompt treatment initiation versus delayed treatment initiation significantly reduced the risk of cardiovascular (HR=0.62; P<0.001) and renal (HR=0.57; P=0.001) events. A history of cardiovascular or renal events was linked to a higher risk of those events in the future. A total of 2051 patients were included in the analysis based on the length of time since their diagnosis (1006 prompt, 1045 delayed). After adjusting for history of cardiovascular events, sex, and age at treatment commencement, prompt treatment initiation significantly reduced the risk of cardiovascular events (HR=0.83; P=0.003) in a multivariate Cox regression analysis. The likelihood of renal events was significantly reduced in the prompt group (P=0.018) in univariate analysis, however this conclusion was weakened in multivariate Cox regression analysis.

Conclusion: This study found that patients with Fabry disease who started treatment with agalsidase alfa immediately had better renal and cardiovascular outcomes than those who started treatment later.

Keywords: cardiomyopathies, early diagnosis, mutation, nephrology, therapeutics