SP004EFFECTS OF LONG-TERM MIGALASTAT TREATMENT ON RENAL FUNCTION BY BASELINE PROTEINURIA IN PATIENTS (PTS) WITH FABRY DISEASE
Bibliographic record
Abstract
INTRODUCTION AND AIMS: Fabry disease is an X-linked disorder of α-galactosidase A (α-Gal A) deficiency, leading to substrate accumulation and multiorgan disease. eGFR declines of up to -6.9 mL/min/1.73 m2/y have been reported in male pts with untreated Fabry disease and high levels of proteinuria. Migalastat, an oral pharmacological chaperone, stabilizes and induces proper folding of specific mutant forms of α-Gal A. In the Phase 3 FACETS study (NCT00925301), migalastat stabilized renal function in enzyme replacement therapy (ERT)-naive pts with Fabry disease and amenable mutations. Here, we evaluated renal outcomes by baseline proteinuria. METHODS: ERT-naive pts who received migalastat during a Phase 2 trial (NCT00526071) or the FACETS study were eligible to continue open-label migalastat 150 mg QOD in a separate Phase 3 extension (NCT01458119). Annualized change rate in eGFRMDRD was calculated based on baseline proteinuria (<100, 100-1000, >1000 mg/24 h); migalastat 150 mg QOD is not intended for use in pts with severe renal impairment. Pts with amenable mutations who entered the Phase 3 extension and received migalastat 150 mg QOD for ≥17 m were analyzed. Results were compared with changes reported in the literature for untreated pts with Fabry disease (natural history cohort; Schiffmann R et al. Nephrol Dial Transplant. 2009;24:2102-11). RESULTS: Median treatment duration ranged from 3.5-4.8 y (max 5.3 y) across proteinuria subgroups. Mean annualized change in eGFR was smaller overall in pts treated with migalastat vs that observed in the natural history cohort across proteinuria categories (Table). Although eGFR declined in all untreated subgroups, increases were seen with migalastat in pts with baseline proteinuria <100 (males) and 100-1000 mg/24 h (males and females). Regardless of treatment, eGFR decreased in pts with baseline proteinuria >1000 mg/24 h; however, pts treated with migalastat had smaller decreases compared to the natural history cohort. CONCLUSIONS: Long-term migalastat treatment (~3-5 years) was generally associated with stable renal function in pts with Fabry disease and amenable mutations, regardless of baseline proteinuria levels.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".