Reduction in kidney function decline and risk of severe clinical events in agalsidase beta-treated Fabry disease patients: A matched analysis from the Fabry Registry
Julie L Batista, Ali Hariri, Manish Maski, Susan Richards, Badari Gudivada, Lewis A Raynor, Elvira Ponce, Christoph Wanner, Robert J Desnick
{"title":"Reduction in kidney function decline and risk of severe clinical events in agalsidase beta-treated Fabry disease patients: A matched analysis from the Fabry Registry","authors":"Julie L Batista, Ali Hariri, Manish Maski, Susan Richards, Badari Gudivada, Lewis A Raynor, Elvira Ponce, Christoph Wanner, Robert J Desnick","doi":"10.1093/ckj/sfae194","DOIUrl":null,"url":null,"abstract":"Background Patients with Fabry disease (FD, α-galactosidase A deficiency or absence) accumulate glycosphingolipids, leading to progressive dysfunction of kidneys, heart and nervous system. Generalisable real-world outcomes following agalsidase beta treatment initiation outside trials are limited. We investigated the associations of long-term agalsidase beta treatment with estimated glomerular filtration rate (eGFR) changes over time and the risk of developing a composite clinical event in a matched analysis of treated and untreated patients with FD. Methods Agalsidase beta-treated adult patients (aged ≥16 years) from the Fabry Registry and adult untreated patients from a natural history cohort were matched 1:1 and X:X (with one occurrence and multiple occurrences of each untreated patient, respectively) by sex, phenotype, age and (for eGFR slope analysis) baseline eGFR. Outcomes included eGFR slope over 5 years and composite clinical event risk (cardiovascular, cerebrovascular or renal event, or death) over 10+ years. As a surrogate indicator of therapeutic response in paediatric patients, the percentage experiencing normalisation in plasma globotriaosylceramide (GL-3) from treatment initiation was assessed in patients aged 2 to <16 years. Results Overall, eGFR slopes for 1:1-matched untreated and treated adult patients (122 pairs [72.1% male]) were −3.19 and −1.47 mL/min/1.73 m2/y, respectively (reduction in rate of decline=53.9%, P=0.007); for X:X-matched (122 untreated/950 treated [59.4% male]) were −3.29 and −1.56 mL/min/1.73 m2/y, respectively (reduction in rate of decline=52.6%, P<0.001). Agalsidase beta treatment was associated with lower risk of clinical events, with hazard ratios of 0.41 (P=0.003) and 0.67 (P=0.008) for 1:1-matched and X:X-matched analyses, respectively. Plasma GL-3 declined markedly in paediatric patients and normalised in most within 6 months of treatment initiation. Conclusion Agalsidase beta treatment preserves kidney function and delays progression to severe clinical events among adult patients with FD. Plasma GL-3 levels analysed in paediatric patients showed normalisation of elevated pre-treatment levels in most patients.","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Kidney Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ckj/sfae194","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background Patients with Fabry disease (FD, α-galactosidase A deficiency or absence) accumulate glycosphingolipids, leading to progressive dysfunction of kidneys, heart and nervous system. Generalisable real-world outcomes following agalsidase beta treatment initiation outside trials are limited. We investigated the associations of long-term agalsidase beta treatment with estimated glomerular filtration rate (eGFR) changes over time and the risk of developing a composite clinical event in a matched analysis of treated and untreated patients with FD. Methods Agalsidase beta-treated adult patients (aged ≥16 years) from the Fabry Registry and adult untreated patients from a natural history cohort were matched 1:1 and X:X (with one occurrence and multiple occurrences of each untreated patient, respectively) by sex, phenotype, age and (for eGFR slope analysis) baseline eGFR. Outcomes included eGFR slope over 5 years and composite clinical event risk (cardiovascular, cerebrovascular or renal event, or death) over 10+ years. As a surrogate indicator of therapeutic response in paediatric patients, the percentage experiencing normalisation in plasma globotriaosylceramide (GL-3) from treatment initiation was assessed in patients aged 2 to <16 years. Results Overall, eGFR slopes for 1:1-matched untreated and treated adult patients (122 pairs [72.1% male]) were −3.19 and −1.47 mL/min/1.73 m2/y, respectively (reduction in rate of decline=53.9%, P=0.007); for X:X-matched (122 untreated/950 treated [59.4% male]) were −3.29 and −1.56 mL/min/1.73 m2/y, respectively (reduction in rate of decline=52.6%, P<0.001). Agalsidase beta treatment was associated with lower risk of clinical events, with hazard ratios of 0.41 (P=0.003) and 0.67 (P=0.008) for 1:1-matched and X:X-matched analyses, respectively. Plasma GL-3 declined markedly in paediatric patients and normalised in most within 6 months of treatment initiation. Conclusion Agalsidase beta treatment preserves kidney function and delays progression to severe clinical events among adult patients with FD. Plasma GL-3 levels analysed in paediatric patients showed normalisation of elevated pre-treatment levels in most patients.
期刊介绍:
About the Journal
Clinical Kidney Journal: Clinical and Translational Nephrology (ckj), an official journal of the ERA-EDTA (European Renal Association-European Dialysis and Transplant Association), is a fully open access, online only journal publishing bimonthly. The journal is an essential educational and training resource integrating clinical, translational and educational research into clinical practice. ckj aims to contribute to a translational research culture among nephrologists and kidney pathologists that helps close the gap between basic researchers and practicing clinicians and promote sorely needed innovation in the Nephrology field. All research articles in this journal have undergone peer review.