Arakawa Makoto, Ikeda Yoshinori, Otaka Hiromichi, Iwashiro Sanghun
Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan.
Mol Genet Metab Rep. 2024 Jul 13;40:101122. doi: 10.1016/j.ymgmr.2024.101122. eCollection 2024 Sep.
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.
法布里病是一种罕见的X连锁遗传性代谢紊乱疾病，其中α-半乳糖苷酶A活性缺乏导致球三糖神经酰胺（Gb3）逐渐蓄积和多系统功能障碍。2006年α-半乳糖苷酶α在日本获批用于治疗法布里病后，一项为期8年的全病例上市后监测（PMS）显示，该治疗耐受性良好，对成年日本患者控制疾病进展有效。目前这项全国性前瞻性观察研究通过在一项为期6.5年的延长调查中纳入在最初8年疗程后继续接受α-半乳糖苷酶α治疗的患者，扩展了最初的PMS。将最初PMS和延长调查中的患者信息作为一个数据集进行评估（观察期：2007年2月至2021年9月）。在最初PMS的493例患者中，129例（45.0%为男性经典型，6.2%为男性非经典型，48.8%为女性杂合子表型）同意参与延长调查并纳入分析。平均治疗时长为9.6年。31例患者（24%）共发生145例药物不良反应（ADR），12例患者（9.3%）发生22例严重ADR。虽然男性患者严重心脏、肾脏或脑血管不良事件的发生率随时间下降，但女性患者仍有严重心脏事件发生，且女性患者在基线时心脏并发症的发生率更高。未发现新的安全问题。此外，长期α-半乳糖苷酶α治疗维持了Gb3浓度的最初降低，且未增加抗α-半乳糖苷酶抗体阳性率。这些发现表明，α-半乳糖苷酶α治疗长期显示出持续的安全性并维持了患者的临床病程。
