Author/Editor		Goláň, Lubor; Goker-Alpan, Ozlem; Holida, Myrl; Kantola, Ikka; Vujkovac, Bojan
Title		Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease
Type		članek
Publication year		2015
Volume		str. p. 3435-3444
ISSN		1177-8881 - Drug design, development and therapy
Language		eng
Abstract		Purpose: Efficacy and safety of agalsidase alfa at 0.2mg/kg weekly were compared with 0.2mg/kg every other week (EOW). Exploratory analyses were performed for 0.4 mg/kg weekly. Patients and methods: This was a 53-week, Phase III/IV, multicenter, open-label study (NCT01124643) in treatment-naïve adults ($18 years) with Fabry disease. Inclusion criteria were left ventricular hypertrophy at baseline, defined as left ventricular mass indexed to height .50 g/m2.7 for males and .47 g/m2.7 for females. Primary endpoint was reduction of left ventricular mass indexed to height as assessed by echocardiography. Secondary endpoints included cardiac (peak oxygen consumption, 6-minute walk test, Minnesota Living with Heart Failure Questionnaire, New York Heart Association classification), renal (Modification of Diet in Renal Disease, estimated glomerular filtration rate), and biomarker (plasma globotriaosylceramide) assessments. Safety endpoints were adverse events and anti-agalsidase alfa antibodies. Results: Twenty patients were randomized to 0.2mg/kg EOW (mean age, 50.3 years; 70% male), 19 to 0.2 mg/kg weekly (51.8 years; 53% male), and 5 to 0.4 mg/kg weekly (49.4 years; 40% male). The mean change in left ventricular mass indexed to height by Week 53 in the 0.2-mg/kg EOW and weekly groups was 3.2 g/m2.7 and 0.5 g/m2.7, with no significant difference between groups. No clinically meaningful changes by Week 53 were found within or between the 0.2-mg/kg groups for peak oxygen consumption, 6-minute walk test, or Minnesota Living with Heart Failure Questionnaire. Two patients in each group improved by $1 New York Heart Association classification. No significant differences were found between 0.2 mg/kg EOW and weekly for mean change in estimated glomerular filtration rate (%1.21 mL/min/1.73 m2 vs %3.32 mL/min/1.73 m2 ) or plasma globotriaosylceramide (%1.05 nmol/mL vs %2.13 nmol/mL), respectively. Infusion-related adverse events were experienced by 25% and 21% in the 0.2-mg/kg EOW and weekly groups. Tachycardia, fatigue, and hypotension were experienced by two or more patients overall. Anti%agalsidase alfa antibodies were detected in 11.4% of patients and neutralizing antibodies in 6.8%. Infusion-related reactions did not appear to be correlated with antibody status. Conclusion: No efficacy or safety differences were found when the approved EOW dosage of agalsidase alfa was increased to weekly administration. Exploratory analyses for 0.4 mg/kg weekly showed similar results
Descriptors		Genetic diseases Genetske bolezni Fabry disease Fabryjeva bolezen
Keywords		adverse events exercise tolerance left ventricular hypertrophy lysosomal storage disorder quality of life renal function neželeni dogodek telesna aktivnost hipertrofija levega ventrikla lisosomska motnja kvaliteta življenja ledvična funkcija