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. 2021 Aug 16:15:3561-3572.
doi: 10.2147/DDDT.S313789. eCollection 2021.

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

Derralynn Hughes  1 , Aleš Linhart  2 , Andrey Gurevich  3 , Vasiliki Kalampoki  3 , Dalia Jazukeviciene  3 , Sandro Feriozzi  4 ; FOS Study Group
Affiliations

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

Derralynn Hughes et al. Drug Des Devel Ther. .

Abstract

Background: The timing of enzyme replacement therapy initiation in patients with Fabry disease is hypothesized to be critical. In this study, we used Fabry Outcome Survey data to assess the impact of prompt versus delayed initiation of treatment with agalsidase alfa on cardiovascular and renal events in patients with Fabry disease.

Methods: Available genetic data at baseline were used to define patients with mutations associated with classical versus late-onset Fabry disease. Time to cardiovascular or renal events, from treatment initiation until 120 months, was compared for patients in prompt versus delayed groups. "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). Kaplan-Meier curves and Log rank tests compared event-free probabilities and time to first event. Multivariate Cox regression estimated hazard ratios (HRs).

Results: Analysis by time from symptom onset included 1374 patients (172 prompt, 1202 delayed). In a multivariate Cox regression analysis, prompt versus delayed treatment initiation significantly reduced the probability of cardiovascular (HR=0.62; P<0.001) and renal (HR=0.57; P=0.001) events. History of cardiovascular or renal events was associated with increased risk of respective events. Analysis by time from diagnosis included 2051 patients (1006 prompt, 1045 delayed). In a multivariate Cox regression analysis, prompt treatment initiation significantly reduced the probability of cardiovascular events (HR=0.83; P=0.003) after adjusting for history of cardiovascular events, sex, and age at treatment initiation. Univariate analysis showed that the probability of renal events was significantly lower in the prompt group (P=0.018); this finding was attenuated in the multivariate Cox regression analysis.

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

Keywords: cardiomyopathies; early diagnosis; mutation; nephrology; therapeutics.

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Conflict of interest statement

DH reports personal fees from Takeda, Sanofi Genzyme, Amicus Therapeutics, Idorsia, Protalix Biotherapeutics, and Freeline Therapeutics, outside the submitted work. AL reports personal fees from Amicus Therapeutics, Avrobio, Sanofi Genzyme, and Takeda, outside the submitted work. AG and VK were employees of Takeda at the time of the study. DJ is an employee of Takeda and is a stockholder of Takeda Pharmaceuticals Company Limited. SF reports personal fees from Takeda, Sanofi Genzyme, and Amicus Therapeutics, outside the submitted work. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Kaplan-Meier curves with Log rank test showing (A) time to first cardiovascular event and (B) time to first renal event for prompt versus delayed agalsidase alfa initiation cohorts, based on time from symptom onset (analysis A).
Figure 2
Figure 2
Kaplan-Meier curves with Log rank test showing (A) time to first cardiovascular event and (B) time to first renal event for prompt versus delayed agalsidase alfa initiation cohorts, based on time from diagnosis (analysis B).
See this image and copyright information in PMC

References

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