Clinical outcomes after switching to migalastat from agalsidase alfa or agalsidase beta in patients with Fabry disease: Post hoc analysis from ATTRACT

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.

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Enzyme replacement therapy in Fabry disease: Comparison of agalsidase alfa and agalsidase beta

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2008.07.002 ◽

2008 ◽

Vol 95 (1-2) ◽

pp. 114-115 ◽

Cited By ~ 15

Author(s):

Atul Mehta ◽

Michael Beck ◽

Christoph Kampmann ◽

Andrea Frustaci ◽

Dominique P. Germain ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Fabry Disease ◽

Replacement Therapy ◽

Agalsidase Beta ◽

Enzyme Replacement ◽

Agalsidase Alfa

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Clinical outcomes of TAVI or SAVR in men and women with aortic stenosis at intermediate operative risk: a post hoc analysis of the randomised SURTAVI trial

EuroIntervention ◽

10.4244/eij-d-20-00303 ◽

2020 ◽

Vol 16 (10) ◽

pp. 833-841

Author(s):

Nicolas M. Van Mieghem ◽

Michael J. Reardon ◽

Steven J. Yakubov ◽

John Heiser ◽

William Merhi ◽

...

Keyword(s):

Aortic Stenosis ◽

Clinical Outcomes ◽

Operative Risk ◽

Men And Women ◽

Post Hoc Analysis ◽

Post Hoc

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Predictors of clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate or placebo: An exploratory post-hoc analysis of COU-AA-302 trial data.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e16529 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e16529-e16529

Author(s):

Dominic Pilon ◽

Ajay S. Behl ◽

Rhiannon Kamstra, ◽

Yongling Xiao ◽

Marie-Helene Lafeuille ◽

...

Keyword(s):

Clinical Outcomes ◽

Gleason Score ◽

Group Performance ◽

Trial Data ◽

Cox Models ◽

Post Hoc Analysis ◽

Opiate Use ◽

Psa Progression ◽

Ecog Ps ◽

Post Hoc

e16529 Background: A post-hoc analysis of COU-AA-302 trial data showed that brief pain inventory (BPI), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and bone metastases were predictors for overall survival in men with mCRPC treated with AA+P. This study aimed to identify baseline predictors of other clinical outcomes. Methods: COU-AA-302 trial data were used to develop predictive models for prostate-specific antigen (PSA) progression, Eastern Cooperative Oncology Group performance status (ECOG PS) deterioration, and opiate use. Associations between baseline factors and outcomes were first assessed using multivariable Cox models among AA+P patients (Step 1). In Step 2, interaction testing was conducted between treatment (AA+P vs. placebo) and each potential predictor (P < 0.2) identified in Step 1. Final Cox models included predictors and any significant interactions (p < 0.05). Results: A total of 1,034 men (525 AA+P; 509 placebo) were included in the analysis. Baseline BPI, PSA, LDH, and ALP were predictors of PSA progression and opiate use regardless of AA+P or placebo with higher values indicating higher risks (all P < 0.05). Younger age, shorter time from luteinizing hormone-releasing hormone to randomization, higher Gleason score, and lower PSA at diagnosis were also associated with higher risks of opiate use: (all P < 0.05). For ECOG PS deterioration, higher baseline BPI, PSA, LDH, and Gleason score, older age, and lower baseline ECOG were associated with higher risks regardless of AA+P or placebo (all P < 0.05). Baseline ALP and site of metastasis also predicted ECOG PS deterioration but the effect varied by treatment (lower risk in AA+P versus placebo; both interactions’ P < 0.05). Conclusions: Predictors of PSA progression, ECOG PS deterioration, and opiate use were identified in AA+P and placebo-treated men with mCRPC. No predictors were associated with worse outcomes for AA+P versus placebo, while the negative impact of certain predictors on ECOG PS was favorably modified by AA+P. Further study is needed on the relationship between AA+P and prognostic factors.

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