Fabry is a rare X-linked metabolic lysosomal disorder caused by deficiency in the enzyme α-galactosidase A (alpha-Gal A) by mutations in the GLA gene, encoding the alpha-Gal A enzyme, which catalyses glycosphingolipids, namely globotriaosylceramide (Gb3). Reduced or absent alpha-Gal A activity leads to accumulation of Gb3 in various organs as well as cellular dysfunction and inflammation causing phsyical symptoms and eventual organ failure. Treatment has been available since 2001 for Fabry patients - first enzyme replacement therapy and since 2016, an oral chaperone therapy, Migalastat. Although the initial trials of Migalastat had some both short and extended outcome treatment comparisons, the overall evidence of clinical efficacy is based on too small numbers considering the heterogeneity of the Fabry patient population as well as the very slow progression of the disease. Though the body of real-world evidence is growing, there is a need for more publications of real-world long-term data on clinical outcomes with a focus on treatment with Migalastat. Research Question: Is the incidence and prevalence of Fabry associated clinical events (FACEs) (cardiac, renal, and cerebrovascular) associated with sex, genotype, phenotype at time of diagnosis, biomarkers, and Fabry specific therapy? Objectives: * To investigate time to first Fabry associated clinical events (FACE) (cardiac, renal, and cerebrovascular) with particular focus on Migalastat clinical outcomes and treatment outcomes preceding Migalastat therapy. * To investigate the incidence and prevalence of FACEs with respect to Fabry specific treatment, Migalastat, ERT or no treatment. * To describe FACEs in accordance with different geno- and phenotypic groups. * To investigate the incidence and time to a first fatal or non-fatal cardiac, renal, and cerebrovascular clinical event, separated by each category. Primary outcomes - Time to first FACE (cardiac, renal, and cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. Secondary outcomes * To investigate the incidence and prevalence of FACEs with respect to Fabry specific treatment, Migalastat, ERT or no treatment. * To describe FACEs in accordance with different geno- and phenotypic groups To investigate the incidence and time to a first fatal or non-fatal cardiac, renal and cerebrovascular clinical event, separated by each category. Exploratory outcomes \- To describe disease progression with focus on organ involvement. The study design is a retrospective clinical and paraclinical follow-up of the Danish National Fabry cohort in the period 01.01.2001-31.12.2022. Patient followed a structured yearly monitoring program as part of routine clincal care.
Study Type
OBSERVATIONAL
Enrollment
115
Rigshospitalet
Copenhagen, Denmark
Time to first individual FACE since confirmed diagnosis (Composite endpoint)
Time to first FACE (cardiac, renal, and cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy.
Time frame: 10 years post baseline
Time to first FACE after initiation of Migalastat treatment (Composite endpoint)
Time to first FACE (cardiac, renal, and cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy.
Time frame: 5 years post baseline
Time to first individual FACE since confirmed diagnosis (cardiac)
Time to first individual FACE (cardiac) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy.
Time frame: 10 years post baseline
Time to first individual FACE after initiation of Migalastat treatment (cardiac)
Time to first individual FACE (cardiac) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy.
Time frame: 5 years post baseline
Time to first individual FACE since confirmed diagnosis (renal)
Time to first individual FACE (renal) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy.
Time frame: 10 years post baseline
Time to first individual FACE after initiation of Migalastat treatment (renal)
Time to first individual FACE (renal) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy.
Time frame: 5 years post baseline
Time to first individual FACE after initiation of Migalastat treatment (cerebrovascular)
Time to first individual FACE (cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy.
Time frame: 5 years post baseline
Time to first individual FACE since confirmed diagnosis (cerebrovascular)
Time to first individual FACE (cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy.
Time frame: 10 years post baseline
Prevalence of FACE since confirmed diagnosis
The prevalence of FACEs since confirmed diagnosis
Time frame: 20 years post baseline
Prevalence of FACE after initiation of Fabry-specific treatment
The prevalence of FACEs after initiation of Fabry-specific treatment
Time frame: 5 years post baseline
Incidence of FACE since confirmed diagnosis
The incidence of FACEs since confirmed diagnosis
Time frame: 20 years post baseline
Incidence of FACE after initiation of Fabry-specific treatment
The incidence of FACEs after initiation of Fabry-specific treatment
Time frame: 5 years post baseline
Incidence of cardiac events since confirmed diagnosis
Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category
Time frame: 20 years post baseline
Incidence of renal events since confirmed diagnosis
Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category
Time frame: 20 years post baseline
Incidence of cerebrovascular events since confirmed diagnosis
Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category
Time frame: 20 years post baseline
Incidence of cardiac events after initiation of Fabry-specific treatment
Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category
Time frame: 5 years post baseline
Incidence of renal events after initiation of Fabry-specific treatment
Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category
Time frame: 5 years post baseline
Incidence of cerebrovascular events after initiation of Fabry-specific treatment
Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category
Time frame: 5 years post baseline
Annualized rate of change in eGFR by CKDEPI-formula since initiation of treatment
Annualized rate of change in eGFR based on the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI) over time to compare between Migalastat-treated, ERT, and untreated patients
Time frame: 20 years post baseline
Annualized rate of change in eGFR by CKDEPI-formula after initiation of Fabry-specific treatment
Annualized rate of change in eGFR based on the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI) over time to compare between Migalastat-treated, ERT, and untreated patients
Time frame: 5 years post baseline
Rapid renal progression of disease since confirmed diagnosis
Prevalence of clinically significant change in mGFR or eGFR defined as rapid progression (Using the KDIGO guidelines ie. sustained decline in GFR by 5 mL/min/1.73 m2/yr) since confirmed diagnosis.
Time frame: 20 years post baseline
Rapid renal progression of disease after initiation of Fabry-specific treatment
Prevalence of clinically significant change in mGFR or eGFR defined as rapid progression (Using the KDIGO guidelines ie. sustained decline in GFR by 5 mL/min/1.73 m2/yr) after initiation for Fabry-specific treatment.
Time frame: 5 years post baseline
Incidence of albuminuria since confirmed diagnosis
The incidence of albuminuria; defined as micro (\> 30 mg/g creatinine) or macroalbuminuria (\>300) by urinary albumin/creatinine ratio (ACR) or urinary 24 h protein excretion.
Time frame: 20 years post baseline
Incidence of albuminuria after initiation of Fabry-specific treatment
The incidence of albuminuria; defined as micro (\> 30 mg/g creatinine) or macroalbuminuria (\>300) by urinary albumin/creatinine ratio (ACR) or urinary 24 h protein excretion.
Time frame: 5 years post baseline
Prevalence of albuminuria since confirmed diagnosis
The prevalence of albuminuria; defined as micro (\> 30 mg/g creatinine) or macroalbuminuria (\>300) by urinary albumin/creatinine ratio (ACR) or urinary 24 h protein excretion.
Time frame: 20 years post baseline
Prevalence of albuminuria after initiation of Fabry-specific treatment
The prevalence of albuminuria; defined as micro (\> 30 mg/g creatinine) or macroalbuminuria (\>300) by urinary albumin/creatinine ratio (ACR) or urinary 24 h protein excretion.
Time frame: 5 years post baseline
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