Fabry Disease
Conditions
Keywords
Cardiovascular Diseases, Renal Disease, Cerebrovascular disease
Brief summary
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.
Interventions
None listed
Sponsors
Amicus Therapeutics
Rigshospitalet, Denmark
Caroline Michaela Kistorp
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Genetically-verified Fabry disease * Age above or equal to 18
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to first FACE after initiation of Migalastat treatment (Composite endpoint) | 5 years post baseline | Time to first FACE (cardiac, renal, and cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. |
| Time to first individual FACE since confirmed diagnosis (Composite endpoint) | 10 years post baseline | Time to first FACE (cardiac, renal, and cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first individual FACE after initiation of Migalastat treatment (cardiac) | 5 years post baseline | Time to first individual FACE (cardiac) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. |
| Time to first individual FACE since confirmed diagnosis (renal) | 10 years post baseline | Time to first individual FACE (renal) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. |
| Time to first individual FACE after initiation of Migalastat treatment (renal) | 5 years post baseline | Time to first individual FACE (renal) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. |
| Time to first individual FACE after initiation of Migalastat treatment (cerebrovascular) | 5 years post baseline | Time to first individual FACE (cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. |
| Time to first individual FACE since confirmed diagnosis (cerebrovascular) | 10 years post baseline | Time to first individual FACE (cerebrovascular) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. |
| Prevalence of FACE since confirmed diagnosis | 20 years post baseline | The prevalence of FACEs since confirmed diagnosis |
| Prevalence of FACE after initiation of Fabry-specific treatment | 5 years post baseline | The prevalence of FACEs after initiation of Fabry-specific treatment |
| Incidence of FACE since confirmed diagnosis | 20 years post baseline | The incidence of FACEs since confirmed diagnosis |
| Incidence of FACE after initiation of Fabry-specific treatment | 5 years post baseline | The incidence of FACEs after initiation of Fabry-specific treatment |
| Incidence of cardiac events since confirmed diagnosis | 20 years post baseline | Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category |
| Incidence of renal events since confirmed diagnosis | 20 years post baseline | Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category |
| Incidence of cardiac events after initiation of Fabry-specific treatment | 5 years post baseline | Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category |
| Incidence of renal events after initiation of Fabry-specific treatment | 5 years post baseline | Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category |
| Incidence of cerebrovascular events after initiation of Fabry-specific treatment | 5 years post baseline | Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category |
| Annualized rate of change in eGFR by CKDEPI-formula since initiation of treatment | 20 years post baseline | 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 |
| Annualized rate of change in eGFR by CKDEPI-formula after initiation of Fabry-specific treatment | 5 years post baseline | 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 |
| Rapid renal progression of disease since confirmed diagnosis | 20 years post baseline | 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. |
| Rapid renal progression of disease after initiation of Fabry-specific treatment | 5 years post baseline | 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. |
| Incidence of albuminuria since confirmed diagnosis | 20 years post baseline | 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. |
| Incidence of albuminuria after initiation of Fabry-specific treatment | 5 years post baseline | 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. |
| Prevalence of albuminuria since confirmed diagnosis | 20 years post baseline | 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. |
| Prevalence of albuminuria after initiation of Fabry-specific treatment | 5 years post baseline | 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. |
| Incidence of cerebrovascular events since confirmed diagnosis | 20 years post baseline | Incidence of cardiac, cerebrovascular, and renal clinical events separately by each specific category |
| Time to first individual FACE since confirmed diagnosis (cardiac) | 10 years post baseline | Time to first individual FACE (cardiac) with particular focus on Migalastat on clinical outcomes and treatment outcomes preceding Migalastat therapy. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Organ-specific decline | 20 years post baseline | Reflecting the montoring program of the annual clinical examinations and questionnaires of the Danish Fabry patients, the study will evaluate the organ-specific change prior to and after initiation of Fabry-specific treatment. |
Countries
Denmark
Outcome results
None listed