title: Weekly enzyme replacement therapy may slow decline of renal function in patients with Fabry disease who are on long-term biweekly dosing.
abstract: This study was performed to determine whether adult male patients with Fabry disease who demonstrate a continuing decline in renal function despite 2 to 4 yr of conventionally dosed agalsidase alfa therapy (0.2 mg/kg every other week [EOW]) show an improved slope of decline with weekly administration using the same dosage. Eleven (27%) of 41 adult male patients with Fabry disease who participated in long-term agalsidase alfa clinical trials and who had demonstrated a slope of decline in estimated GFR (eGFR) of > or =5 ml/min per 1.73 m(2)/yr while receiving long-term treatment with agalsidase alfa at the currently recommended dosage of 0.2 mg/kg, infused EOW, were enrolled in this open-label, prospective study. Patients were switched from EOW to weekly infusions and followed for an additional 24 mo. Before switching to weekly dosing, eGFR was 53.7 +/- 6.3 ml/min per 1.73 m(2) (mean +/- SEM), and mean rate of change in eGFR was -8.0 +/- 0.8 ml/min per 1.73 m(2)/yr. During the 24-mo follow-up period after switching to weekly dosing, the mean rate of change in eGFR was observed to slow to -3.3 +/- 1.4 ml/min/1.73 m(2)/yr (P = 0.01 versus EOW). After switching to weekly dosing, three patients demonstrated an improvement in eGFR and six patients demonstrated a slowing in the rate of eGFR decline; only two patients failed to improve their eGFR slope. A multiple regression model confirmed that the weekly infusion regimen was the strongest explanatory variable for the change in eGFR (P = 0.0008), with a weaker contribution from the concomitant use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (P = 0.02). These results suggest that weekly infusions of agalsidase alfa at a dosage of 0.2 mg/kg may be beneficial in the subgroup of patients who have Fabry disease and whose kidney function continues to decline after 2 to 4 yr or more of standard EOW dosing.
authors.affiliation: Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 3D03, 9000 Rockville Pike, Bethesda, MD 20892-1260, USA. rs4e@nih.gov
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.forename: Hasan
authors.initials: H
authors.lastname: Askari
authors.forename: Margaret
authors.initials: M
authors.lastname: Timmons
authors.forename: Chevalia
authors.initials: C
authors.lastname: Robinson
authors.forename: William
authors.initials: W
authors.lastname: Benko
authors.forename: Roscoe O
authors.initials: RO
authors.lastname: Brady
authors.forename: Markus
authors.initials: M
authors.lastname: Ries
mesh_terms: D000328:Adult; D000906:Antibodies / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000795:Fabry Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy; D011994:Recombinant Proteins; D013995:Time; D000519:alpha-Galactosidase / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
chemical_list: D000906:Antibodies; D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase