The effectiveness of long-term agalsidase alfa therapy in the treatment of Fabry nephropathy

Abstract

Background and objectives: Fabry disease is a rare X-linked disease with multisystemic manifestations. This study investigated the effectiveness of long-term enzyme replacement therapy with agalsidase alfa in Fabry nephropathy treatment.

Design, setting, participants, & measurements: In this observational study, data on patients receiving agalsidase alfa (0.2 mg/kg every other week) were extracted from the Fabry Outcome Survey, an international registry of patients with Fabry disease. Serum creatinine and estimated GFR (eGFR) at baseline and after ≥5 years of treatment were assessed; 24-hour urinary protein excretion and BP measurements were also reviewed. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula. Patients with an eGFR <30 ml/min per 1.73 m(2) were excluded.

Results: Renal function was assessed in 208 patients (mean enzyme replacement therapy, 7.4 years; range, 5.0-11.2 years). Mean yearly change in eGFR was -2.2 ml/min per 1.73 m(2) in men and -0.7 ml/min per 1.73 m(2) in women (95% confidence limits, -2.8; -1.7 and -1.4; 0.0, respectively). Patients with 24-hour protein excretion >1 g/24 h had poorer renal function at baseline and follow-up compared with patients with protein excretion of 500-1000 mg/24 h or with proteinuria <500 mg/24 h. Renal function was worse in patients with baseline arterial hypertension, and there was a more rapid yearly decline compared with normotensive patients.

Conclusions: This study suggests that long-term agalsidase alfa therapy is able to stabilize the rate of Fabry nephropathy progression in women and is associated with a mild to moderate decline of renal function in men.

Figure 1.

Flow chart of patient disposition. Data on creatinine concentrations at baseline and after ≥5 years of treatment were available for 208 of 1120 agalsidase alfa–treated patients. For clinical investigation, the cohort of patients was subdivided according to renal function (Kidney Disease Outcomes Quality Initiative stages), to arterial BP and to urinary protein excretion at baseline. FOS, Fabry Outcome Survey; eGFR, estimated GFR; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration.

Figure 2.

Graph showing the line plots of estimated GFR (eGFR) (mean ± SD) from baseline and throughout the follow-up in patients treated with agalsidase alfa. The upper line represents male patients and the lower line represents female patients. Numbers of patients in each group are shown in parentheses.