PDF(Pubmed)
Abstract：
Fabry disease is a rare inherited X-linked metabolic disorder in which deficient alpha-galactosidase A activity causes progressive build-up of globotriaosylceramide (Gb3) and multi-system dysfunction. Following approval of agalsidase alfa for Fabry disease in Japan in 2006, an 8-year all-case post-marketing surveillance (PMS) showed that the treatment was well tolerated and effective for managing disease progression in adult Japanese patients. The present nationwide prospective observational study extended the initial PMS by enrolling patients who continued agalsidase alfa treatment after the initial 8-year period in a 6.5-year extension survey. Patient information from the initial PMS and the extension survey was evaluated as a single data set (observation period: February 2007-September 2021). Of 493 patients in the initial PMS, 129 (45.0% male classic, 6.2% male non-classic, 48.8% female heterozygous phenotype) consented to participate in the extension survey and were included in the analysis. The mean duration of treatment was 9.6 years. A total of 145 adverse drug reactions (ADRs) occurred in 31 patients (24%), and 22 serious ADRs occurred in 12 patients (9.3%). Although serious cardiac, renal, or cerebrovascular adverse events decreased in frequency over time in male patients, serious cardiac events continued to occur in female patients, who showed higher incidence of cardiac complications at baseline. No new safety concerns were identified. Additionally, long-term agalsidase alfa treatment sustained the initial reduction in Gb3 concentrations without increasing the rate of anti-agalsidase antibody positivity. These findings suggest that agalsidase alfa treatment demonstrates continued safety and sustains patients\' clinical course over the long term.
摘要：
Fabry病是一种罕见的遗传性X连锁代谢疾病，其中α-半乳糖苷酶A活性不足会导致球形核糖神经酰胺（Gb3）的进行性积累和多系统功能障碍。在2006年日本批准用于法布里病的半乳糖苷酶之后，为期8年的全病例上市后监测（PMS）表明，该治疗具有良好的耐受性，并且可以有效地管理成年日本患者的疾病进展。当前的全国性前瞻性观察性研究通过在6.5年的扩展调查中招募在最初的8年后继续进行agalsidasealfa治疗的患者来扩展最初的PMS。将来自初始PMS和扩展调查的患者信息作为单一数据集进行评估（观察期：2007年2月至2021年9月）。在最初的PMS中的493名患者中，129(45.0%男性经典，6.2%男性非经典，48.8％的女性杂合表型）同意参加扩展调查并纳入分析。平均治疗时间为9.6年。31例患者（24%）共发生145例药物不良反应（ADR），12例患者发生22例严重不良反应(9.3%).虽然严重的心脏，肾,或脑血管不良事件的频率随着时间的推移男性患者减少，女性患者继续发生严重心脏事件，基线时心脏并发症发生率较高。没有发现新的安全问题。此外,长期的半乳糖苷酶α治疗维持了Gb3浓度的初始降低，而没有增加抗半乳糖苷酶抗体阳性率。这些发现表明，半乳糖苷酶α治疗显示出持续的安全性，并可长期维持患者的临床病程。
