Department of Public Health, Chair of Nephrology, University Federico II of Naples, Via Pansini 5, 80131, Naples, Italy.
IRCCS SDN, Naples, Italy.
Eur J Hum Genet. 2020 Dec;28(12):1662-1668. doi: 10.1038/s41431-020-0677-x. Epub 2020 Jul 9.
The treatment options for Fabry disease (FD) are enzyme replacement therapy (ERT) with agalsidase alfa or beta, and the oral pharmacological chaperone migalastat. Since few data are available on the effects of switching from ERT to migalastat, we performed a single-center observational study on seven male Fabry patients (18-66 years) to assess the effects of the switch on renal, cardiac, and neurologic function, health status, pain, lyso-Gb3, α-Gal A activity and adverse effects. Data were retrospectively collected at time of diagnosis of FD (baseline, T0), and after 12 months of ERT (T1), and prospectively after 1 year of therapy with migalastat (T2). No patient died or reported renal, cardiac, or cerebrovascular events during the study period. The predefined measures for cardiac, renal and neurologic function, and FD-related symptoms and questionnaires were stable between baseline and the switch, and remained unchanged with migalastat. However, a significant improvement was observed in left ventricular mass index from baseline to T2 (p = 0.016), with a significative difference between the treatments (p = 0.028), and in median proteinuria from T2 vs T1 (p = 0.048). Moreover, scores of the BPI improved from baseline to T1, and remained stable with migalastat. Plasma lyso-Gb3 levels significantly decreased from baseline to T1 (P = 0.007) and T2 (P = 0.003), while did not significantly differ between the two treatments. α-Gal A activity increased from T0 to T2 (p < 0.0001). The frequency of adverse effects under migalastat and ERT was comparable (28% for both drugs). In conclusion, switching from ERT to migalastat is valid, safe and well tolerated.
法布雷病（FD）的治疗选择包括使用阿加糖酶α或β进行酶替代疗法（ERT），以及口服药物伴侣米加司他汀。由于关于从ERT 切换到米加司他汀的效果的数据很少，我们对 7 名男性 FD 患者（18-66 岁）进行了一项单中心观察性研究，以评估该切换对肾脏、心脏和神经系统功能、健康状况、疼痛、溶酶体-Gb3、α-Gal A 活性和不良反应的影响。数据在 FD 诊断时（基线，T0）、ERT 治疗 12 个月后（T1）以及米加司他汀治疗 1 年后（T2）进行回顾性收集。在研究期间，没有患者死亡或报告肾脏、心脏或脑血管事件。心脏、肾脏和神经系统功能以及 FD 相关症状和问卷的预定措施在基线和切换时保持稳定，并且在米加司他汀治疗期间保持不变。然而，从基线到 T2，左心室质量指数有显著改善（p=0.016），且两种治疗之间存在显著差异（p=0.028），T2 与 T1 相比，蛋白尿中位数也有所下降（p=0.048）。此外，从基线到 T1，BPI 评分有所改善，并且在米加司他汀治疗期间保持稳定。从基线到 T1（P=0.007）和 T2（P=0.003），血浆溶酶体-Gb3 水平显著下降，而两种治疗之间无显著差异。α-Gal A 活性从 T0 增加到 T2（p<0.0001）。米加司他汀和 ERT 的不良反应频率相当（两种药物均为 28%）。总之，从 ERT 切换到米加司他汀是有效、安全且耐受良好的。
