title: Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch-2-Year Follow-Up.
abstract: Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3-0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C-based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used.
authors.affiliation: Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, Interdisciplinary Fabry Center Münster.
authors.forename: Malte
authors.initials: M
authors.lastname: Lenders
authors.affiliation: Department of Medicine, Division of Nephrology and.
authors.forename: Sima
authors.initials: S
authors.lastname: Canaan-Kühl
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany; Department of Medicine, Divisions of Cardiology and Nephrology, Comprehensive Heart Failure Center, Fabry Center for Interdisciplinary Therapy and.
authors.forename: Johannes
authors.initials: J
authors.lastname: Krämer
authors.affiliation: Department of Neurology.
authors.forename: Thomas
authors.initials: T
authors.lastname: Duning
authors.affiliation: Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, Interdisciplinary Fabry Center Münster.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Reiermann
authors.affiliation: Department of Medicine, Divisions of Cardiology and Nephrology, Comprehensive Heart Failure Center, Fabry Center for Interdisciplinary Therapy and Department of Neurology, University of Würzburg, Würzburg, Germany;
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
authors.affiliation: Department of Cardiovascular Medicine, Division of Cardiology.
authors.forename: Jörg
authors.initials: J
authors.lastname: Stypmann
authors.affiliation: Department of Medicine, Division of Cardiology, Charité, Campus Virchow-Klinikum, Berlin, Germany;
authors.forename: Daniela
authors.initials: D
authors.lastname: Blaschke
authors.affiliation: Department of Medicine, Divisions of Cardiology and Nephrology, Comprehensive Heart Failure Center, Fabry Center for Interdisciplinary Therapy and Department of Neurology, University of Würzburg, Würzburg, Germany;
authors.forename: Nurcan
authors.initials: N
authors.lastname: Üçeyler
authors.affiliation: Institute of Epidemiology and Social Medicine, and.
authors.forename: Hans-Werner
authors.initials: HW
authors.lastname: Hense
authors.affiliation: Institute of Sports Medicine, Molecular Genetics of Cardiovascular Disease, University Hospital Münster, Münster, Germany;
authors.forename: Stefan-Martin
authors.initials: SM
authors.lastname: Brand
authors.affiliation: Department of Medicine, Divisions of Cardiology and Nephrology, Comprehensive Heart Failure Center, Fabry Center for Interdisciplinary Therapy and.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.affiliation: Department of Medicine, Divisions of Cardiology and Nephrology, Comprehensive Heart Failure Center, Fabry Center for Interdisciplinary Therapy and Katharinen-Hospital Unna, Unna, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Weidemann
authors.affiliation: Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, Interdisciplinary Fabry Center Münster, Eva.Brand@ukmuenster.de.
authors.forename: Eva
authors.initials: E
authors.lastname: Brand
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D000328:Adult; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D057915:Drug Substitution / Q000009:adverse effects; D056947:Enzyme Replacement Therapy / Q000009:adverse effects; D000795:Fabry Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000503:physiopathology*; D012189:Retrospective Studies; D012709:Serum Albumin / Q000378:metabolism; D012720:Severity of Illness Index; D000519:alpha-Galactosidase / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D055316:Cystatin C; D007527:Isoenzymes; D012709:Serum Albumin; D003404:Creatinine; D000519:alpha-Galactosidase; C459420:agalsidase beta
keywords: Fabry’s disease; chronic kidney disease; creatinine clearance; cystatin C clearance; enzyme; outcomes; replacement therapy