BACKGROUND: We analysed 5-year treatment with
agalsidase alfa enzyme replacement therapy in patients with
Fabry's disease who were enrolled in the Fabry Outcome Survey observational database (FOS). METHODS: Baseline and 5-year data were available for up to 181 adults (126 men) in FOS. Serial data for
cardiac mass and function,
renal function,
pain, and quality of life were assessed. Safety and sensitivity analyses were done in patients with baseline and at least one relevant follow-up measurement during the 5 years (n=555 and n=475, respectively). FINDINGS: In patients with baseline
cardiac hypertrophy, treatment resulted in a sustained reduction in
left ventricular mass (LVM) index after 5 years (from 71.4 [SD 22.5] g/m(2.7) to 64.1 [18.7] g/m(2.7), p=0.0111) and a significant increase in midwall fractional
shortening (MFS) from 14.3% (2.3) to 16.0% (3.8) after 3 years (p=0.02). In patients without baseline
hypertrophy, LVM index and MFS remained stable.
Mean yearly fall in
estimated glomerular filtration rate versus baseline after 5 years of
enzyme replacement therapy was -3.17 mL/min per 1.73 m(2) for men and -0.89 mL/min per 1.73 m(2) for women.
Average pain, measured by
Brief Pain Inventory score, improved significantly, from 3.7 (2.3) at baseline to 2.5 (2.4) after 5 years (p=0.0023). Quality of life, measured by deviation scores from normal EuroQol values, improved significantly, from -0.24 (0.3) at baseline to -0.17 (0.3) after 5 years (p=0.0483). Findings were confirmed by
sensitivity analysis. No unexpected safety concerns were identified. INTERPRETATION: By comparison with historical natural history data for patients with
Fabry's disease who were not treated with
enzyme replacement therapy, long-term treatment with
agalsidase alfa leads to substantial and sustained clinical benefits. FUNDING: Shire
Human Genetic Therapies AB.
