title: A randomised, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of three dosing schedules of agalsidase alfa enzyme replacement therapy for Fabry disease.
abstract: Anecdotal reports suggest that the currently approved dosing interval of agalsidase alfa (0.2 mg/kg/2 weeks) for Fabry disease treatment is too long. This randomised, double-blind, placebo-controlled, crossover study investigated three altered dosing intervals. 18 Fabry patients received three agalsidase alfa dosing schedules, each for four weeks (A: 0.2 mg/kg∗2 weeks, B: 0.1 mg/kg/week, C: 0.2 mg/kg/week). Health state, pain levels, sweat volume and latency and plasma and urinary globotriaosylceramide levels were recorded throughout the study. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores. A trend toward increased sweat volume on QSART testing, and reduced urine globotriaosylceramide concentration were seen with treatment schedule C. Agalsidase alfa was safe and well tolerated with all schedules. In conclusion, the primary analyses did not find weekly infusions of agalsidase alfa to be statistically better than the approved dosing schedule however the data indicates that further studies with more patients over a longer period are required to more accurately determine the optimum dose and schedule.
authors.affiliation: Department of Haematology, Royal Free Campus, University College London, Rowland Hill Street, London NW3 2PF, UK. rmgvdah@ucl.ac.uk
authors.forename: D A
authors.initials: DA
authors.lastname: Hughes
authors.forename: P B
authors.initials: PB
authors.lastname: Deegan
authors.forename: A
authors.initials: A
authors.lastname: Milligan
authors.forename: N
authors.initials: N
authors.lastname: Wright
authors.forename: L H
authors.initials: LH
authors.lastname: Butler
authors.forename: A
authors.initials: A
authors.lastname: Jacobs
authors.forename: A B
authors.initials: AB
authors.lastname: Mehta
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D018592:Cross-Over Studies; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016896:Treatment Outcome; D000519:alpha-Galactosidase / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase