title: Patients with Fabry disease after enzyme replacement therapy dose reduction versus treatment switch.
abstract: Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3-0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m(2) (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0-606) mg/g to 216 (0-2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate.
authors.affiliation: Department of Medicine, Divisions of Cardiology and Nephrology, Comprehensive Heart Failure Center, Fabry Center for Interdisciplinary Therapy, and.
authors.forename: Frank
authors.initials: F
authors.lastname: Weidemann
authors.forename: Johannes
authors.initials: J
authors.lastname: Krämer
authors.forename: Thomas
authors.initials: T
authors.lastname: Duning
authors.forename: Malte
authors.initials: M
authors.lastname: Lenders
authors.forename: Sima
authors.initials: S
authors.lastname: Canaan-Kühl
authors.forename: Alice
authors.initials: A
authors.lastname: Krebs
authors.forename: Hans
authors.initials: H
authors.lastname: Guerrero González
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
authors.forename: Nurcan
authors.initials: N
authors.lastname: Üçeyler
authors.forename: Markus
authors.initials: M
authors.lastname: Niemann
authors.forename: Stefan
authors.initials: S
authors.lastname: Störk
authors.forename: Michael
authors.initials: M
authors.lastname: Schelleckes
authors.forename: Stefanie
authors.initials: S
authors.lastname: Reiermann
authors.forename: Jörg
authors.initials: J
authors.lastname: Stypmann
authors.forename: Stefan-Martin
authors.initials: SM
authors.lastname: Brand
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.forename: Eva
authors.initials: E
authors.lastname: Brand
mesh_terms: D000328:Adult; D000368:Aged; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007527:Isoenzymes / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins; D000519:alpha-Galactosidase / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase; C459420:agalsidase beta