Cardio- Renal Outcomes With Long- Term Agalsidase Alfa Enzyme Replacement Therapy: A 10- Year Fabry Outcome Survey (FOS) Analysis
Bibliographic record
Abstract
Uma Ramaswami,1 Michael Beck,2 Derralynn Hughes,1 Christoph Kampmann,2 Jaco Botha,3 Guillem Pintos-Morell,4 Michael L West,5 Dau-Ming Niu,6 Kathy Nicholls,7,8 Roberto Giugliani9 On behalf of the FOS Study Group 1Royal Free London NHS Foundation Trust, Lysosomal Disorders Unit, Institute of Immunity and Transplantation, London, UK; 2Centre for Paediatric and Adolescent Medicine, University Medical Centre, University of Mainz, Mainz, Germany; 3Department of Biostatistics and Programming, Takeda, Zug, Switzerland; 4Centre for Rare Diseases, University Hospital Vall d’Hebron, Barcelona, CIBERER-GCV08_IGTP Research Institute and Teaching Unit Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain; 5Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; 6Department of Paediatrics, Taipei Veterans General Hospital, Taipei, Taiwan; 7Department of Nephrology, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia; 8Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia; 9Medical Genetics Service HCPA, Department of Genetics, UFRGS, and INAGEMP, Porto Alegre, BrazilCorrespondence: Uma RamaswamiLysosomal Disorders Unit, Institute of Immunity and Transplantation, 2nd Floor, Royal Free Hospital, Pond Street, London NW3 2QG, UKTel +44 207 794 0500 Ext 22492Fax +44 207 317 7665Email uma.ramaswami@nhs.netPurpose: Following the publication of 5-year agalsidase alfa enzyme replacement therapy (ERT) outcomes data from the Fabry Outcome Survey (FOS), 10-year data were analyzed.Patients and methods: FOS (ClinicalTrials.gov identifier: NCT03289065) data (April 2001 to August 2018) were retrospectively analyzed. Estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) were analyzed after treatment start (baseline) for patients with ≥3 measurements, including baseline and year 10.Results: Median (range) age (years) of the evaluable treated renal cohort at treatment start was 48.8 (17.9–67.3) for females (n=62), 34.4 (18.0–66.8) for males (n=90). With eGFR ≥60 mL/min/1.73 m2 at baseline, mean (95% CI) rate of eGFR change (eGFR/year) over 10 years was relatively stable in females (n=52; −0.55 [−1.12, +0.01]) and slightly declined in males (n=79; −1.99 [−2.45, −1.54]). With impaired kidney function (eGFR <60 mL/min/1.73 m2) at baseline, mean (95% CI) eGFR/year was stable in females (n=10; −0.14 [−1.43, +1.15]) and slightly declined in males (n=11; −2.79 [−4.01, −1.56]) over 10 years. Median (range) age (years) of the evaluable treated cardiac cohort at treatment start was 46.7 (3.7–67.3) for females (n=34), 28.2 (4.0–54.2) for males (n=35). With left ventricular hypertrophy (LVH; LVMI >48 g/m2.7 in females, >50 g/m2.7 in males) at baseline, mean (95% CI) LVMI/year slightly increased over 10 years in females (n=18; +1.51 [+0.91, +2.12]) and males (n=14; +0.87 (+0.19, +1.55). Without LVH at baseline, mean (95% CI) LVMI/year was stable in females (n=16; +0.52 [−0.13, +1.17]) and males (n=21; +0.57 [+0.02, +1.13]) over 10 years.Conclusion: Agalsidase alfa-treated patients with 10-year FOS data and preserved kidney function and/or normal LVMI at baseline remained largely stable; those with decreased kidney function or LVH at baseline experienced modest declines in renal function and/or increases in LVMI.Keywords: agalsidase alfa, enzyme replacement therapy, Fabry disease, cardio-renal outcomes
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".