Treatment of Fabry Disease: Outcome of a Comparative Trial with Agalsidase Alfa or Beta at a Dose of 0.2 mg/kg

Two different enzyme preparations, agalsidase alfa (Replagal(TM), Shire) and beta (Fabrazyme(TM), Genzyme), are registered for treatment of Fabry disease. We compared the efficacy of and tolerability towards the two agalsidase preparations administered at identical protein dose in a randomized controlled open label trial.Thirty-four Fabry disease patients were treated with either agalsidase alfa or agalsidase beta at equal dose of 0.2 mg/kg biweekly. Primary endpoint was reduction in left ventricular mass after 12 and 24 months of treatment. Other endpoints included occurrence of treatment failure (defined as progression of cardiac, renal or cerebral disease), glomerular filtration rate, pain, anti-agalsidase antibodies, and globotriaosylceramide levels in plasma and urine. After 12 and 24 months of treatment no reduction in left ventricular mass was seen, which was not different between the two treatment groups. Also, no differences in glomerular filtration rate, pain and decline in globotriaosylceramide levels were found. Antibodies developed only in males (4/8 in the agalsidase alfa group and 6/8 in the agalsidase beta group). Treatment failure within 24 months of therapy was seen in 8/34 patients: 6 male patients (3 in each treatment group) and 2 female patients (both agalsidase alfa). The occurrence of treatment failures did not differ between the two treatment groups; chi(2) = 0.38 p = 0.54.Our study revealed no difference in reduction of left ventricular mass or other disease parameters after 12 and 24 months of treatment with either agalsidase alfa or beta at a dose of 0.2 mg/kg biweekly. Treatment failure occurred frequently in both groups and seems related to age and severe pre-treatment disease.International Standard Randomized Clinical Trial ISRCTN45178534 [http://www.controlled-trials.com/ISRCTN45178534]

DISCORDANT EFFECTS OF ENALAPRIL AND LISINOPRIL ON SYSTEMIC AND RENAL HEMODYNAMICS

Obective: To investigate whether there are quantitative differences between the angiotensin converting enzyme (ACE) inhibitors enalapril and lisinopril with respect to their influence on renal versus systemic hemodynamics in humans. Methods: This was a 12-month, single-blind crossover study in which eight patients with essential hypertension were examined. The main outcome measures were blood pressure and renal hemodynamics during ACE inhibition and/or angiotensin II infusion. Results: The decrease in blood pressure was dose dependent and not significantly different between both drugs. However, with the same blood pressure reduction effective renal plasma how (ERPF) rose more and filtration fraction (PE) and renovascular resistance (RVR) decreased more after administration of enalapril (20 mg) than after administration of lisinopril (20 mg) (ERPF: 21.9% +/- 2.0% versus 4.4% +/- 2.5%, p = 0.018; FF: -16.7% +/- 2.8% versus -6.6% +/- 2.5%, p = 0.028; RVR: -28.1% +/- 3.1% versus - 18.5% +/- 3.7%, p = 0.018). During angiotensin LI infusion, with a similar increase in systemic blood pressure, the change in ERPF, FF, and RVR again was more pronounced during enalapril than during lisinopril (ERPF: - 14.6% +/- 2.9% versus - 7.8% +/- 3.3%, p = 0.018; FF: 18.3% +/- 5.9% versus 12.8% +/- 6.0%, p = 0.028; RVR: 36.7% +/- 8.1% versus 21.9% +/- 4.3%, p = 0.018). Conclusions: We conclude that in a situation of a comparable systemic blood pressure reduction, enalapril has greater effects on renal hemodynamics than lisinopril This finding may have implications for the choice of a certain ACE inhibitor in specific disease conditions