title: Treatment of Fabry disease with different dosing regimens of agalsidase: effects on antibody formation and GL-3.
abstract: Two different enzyme preparations are used for the treatment of Fabry disease patients, agalsidase alpha (Replagal, Shire) and agalsidase beta (Fabrazyme, Genzyme). Therapeutic efficacy of both products has been variable probably due to differences in gender, severity, age and other patient characteristics. We studied the occurrence of alpha-Gal A antibodies and their effect on urinary and plasma globotriaosylceramide (GL-3), plasma chitotriosidase and clinical outcome in 52 patients after 12 months of treatment with either 0.2mg/kg agalsidase alppha (10 males, 8 females) or beta (8 males, 5 females) or 1.0mg/kg agalsidase beta (10 males, 11 females). Antibodies were detected in 18/28 male patients after 6 months. None of the females developed antibodies. Following 12 months of 0.2mg/kg treatment, urinary GL-3 decreased in antibody negative (AB-) but increased in antibody positive (AB+) patients. Treatment with 1.0mg/kg gave a reduction in urinary GL-3 in both AB- and AB+ patients. Levels of plasma GL-3 and chitotriosidase decreased in all patient groups. Twelve months of 0.2mg/kg treatment did not change renal function or left ventricular mass. Further, no change in renal function was seen following 1.0mg/kg treatment and left ventricular mass decreased in both AB- and AB+ patients. In summary, alpha-Gal A antibodies frequently develop in male Fabry disease patients and interfere with urinary GL-3 excretion. Infusion of a dose of 1.0mg/kg results in a more robust decline in GL-3, less impact, if any of antibodies, stable renal function and reduction of LVMass.
authors.affiliation: Department of Internal Medicine/Endocrinology and Metabolism, Academic Medical Center, F4-224, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Anouk C
authors.initials: AC
authors.lastname: Vedder
authors.forename: Frank
authors.initials: F
authors.lastname: Breunig
authors.forename: Wilma E
authors.initials: WE
authors.lastname: Donker-Koopman
authors.forename: Kevin
authors.initials: K
authors.lastname: Mills
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Young
authors.forename: Bryan
authors.initials: B
authors.lastname: Winchester
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: Ten Berge
authors.forename: Johanna E M
authors.initials: JE
authors.lastname: Groener
authors.forename: Johannes M F G
authors.initials: JM
authors.lastname: Aerts
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.forename: Carla E M
authors.initials: CE
authors.lastname: Hollak
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood / Q000494:pharmacology; D000917:Antibody Formation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000795:Fabry Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000652:urine; D005260:Female; D006352:Heart Ventricles / Q000473:pathology; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy / Q000139:chemically induced; D007668:Kidney / Q000502:physiology; D008297:Male; D008875:Middle Aged; D017211:Treatment Failure; D014281:Trihexosylceramides / Q000097:blood / Q000378:metabolism* / Q000652:urine; D000519:alpha-Galactosidase / Q000008:administration & dosage* / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000906:Antibodies; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D006596:Hexosaminidases; C086400:chitotriosidase; D000519:alpha-Galactosidase