Efficacy and safety of long-term enzyme replacement therapy with agalsidase alfa or agalsidase beta in adult patients with Fabry disease

Moiseev A.: Sechenov First Moscow State Medical University

Bulanov N.: Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia

Tao E.: Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia

Mershina E.: Moscow State University

Sholomova V.: Sechenov First Moscow State Medical University

Moiseev S.: Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical University, Moscow, Russia

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Summary

Aim

To evaluate the efficacy and safety of long-term enzyme replacement therapy (ERT) in the Russian population of patients with Fabry disease (FD).

Material and methods

We enrolled 29 adult patients with FD (17 males and 12 females; median age 38.0 years) who received ERT with agalsidase alfa or agalsidase beta for a median of 63.5 months (IQR 51.0-75.0). The primary combined end-point included rhythm disorders (atrial fibrillation, sustained supraventricular and ventricular tachycardia), heart failure, stroke, initiation of renal replacement therapy, and death from all causes. We also studied changes in neuropathic pain, albuminuria, estimated glomerular filtration rate (CFR), left ventricular myocardial mass index, and Lyso-GL3 in dried blood spots level. Myocardial mass was measured by MRI.

Results

Clinical outcomes during ERT have occurred in 3 (10.3%) patients (all males). Neuropathic pain after initiation of ERT has improved in 15 (60.0%) patients. Albuminuria was stable in 15 (60.0%) of 20 patients who did not receive renal replacement therapy at baseline, whereas median GFR decline rate was -3,2 ml/min/1,73 m2 per year. Median left ventricular myocardial mass index has decreased from 96.0 to 77.0 g/m2 (p<0.01). Changes in this parameter were also statistically significant in subgroups of males and females, patients treated with agalsidase alfa or agalsidase beta, and patients with left ventricular hypertrophy. In males, ERT resulted in decline of median Lyso-GL3 level from 69.3 to 17.0 ng/ml (p=0.05). There were no adverse events requiring interruption or discontinuation of ERT.

Conclusion

90% of adult patients with FD remained alive and event-free during long-term ERT (median 5 years).

Key words

Fabry disease, enzyme replacement therapy, agalsidase alfa, agalsidase beta.