脑室内 idursulfase 治疗神经元病型黏多糖贮积症 II 型的上市后监测中期分析：日本临床实践中的安全性与有效性
Interim analysis of post-marketing surveillance study of intracerebroventricular idursulfase therapy for neuronopathic mucopolysaccharidosis type II: Safety and effectiveness in clinical practice in Japan
黏多糖贮积症 II 型（MPS II）因 IDS 基因突变导致酶缺乏，多数神经元病型患者出现进行性神经退化，而静脉给酶难以穿过血脑屏障。脑室内注射 idursulfase beta 于 2021 年在日本获批，直接向脑室递送。本上市后监测纳入 2021 年 4 月至 2024 年 8 月所有接受治疗的患者（安全性人群 36 例，有效性人群 35 例）。脑脊液硫酸乙酰肝素从基线 7.36 μg/mL 降至第 24 周 3.19 μg/mL 并维持至 100 周；3 岁前开始治疗者发育年龄进展与健康儿童相当，较晚开始者无此获益。不良事件发生率 55.6%，主要为发热，发生 2 例操作相关严重不良事件（细菌性脑膜炎、装置相关感染），无死亡。提示该疗法安全可控，且早治疗更有利。
为什么推荐给您：已获批疗法的上市后监测，证实长期有效性与早期治疗窗口，属已知疗法的真实世界数据扩展
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摘要Abstract
Mucopolysaccharidosis type II (MPS II) results from iduronate-2-sulfatase (IDS) enzyme deficiency due to IDS gene mutations. Most patients with neuronopathic MPS II experience progressive neurological decline; however, effectiveness of standard treatment, intravenous idursulfase, is limited by blood-brain barrier transfer. Intracerebroventricular (ICV) idursulfase beta, approved in Japan in 2021, directly delivers idursulfase beta into cerebral ventricles. This post-marketing surveillance reports long-term effectiveness and safety of ICV idursulfase beta (30 mg every 4 weeks) in all treated patients from April 2021 through August 2024. Outcomes included cerebrospinal fluid (CSF) heparan sulfate (HS) levels (quarterly), developmental age (DA; Kyoto Scale of Psychological Development, annually), and safety. Thirty-seven Japanese male patients across 21 sites were enrolled (safety population n = 36; effectiveness population n = 35). Mean CSF HS concentrations decreased from 7.36 to 3.19 μg/mL from baseline to week 24, with reduction sustained through week 100. Patients who initiated treatment within 3 years of age had DA progression aligned with healthy cohorts, regardless of mutation type; however, those starting later had no comparable benefit. Adverse events (AEs) occurred in 20 patients (55.6%). Procedure-related serious AEs (SAEs) occurred in 2 patients (bacterial meningitis, device-related infection, pyrexia). Treatment-related AEs affected 14 patients (38.9%), mainly pyrexia (27.8%, including one SAE). One SAE (membranous glomerulonephritis) was not intervention related. No deaths, anaphylaxis, or anti-IDS antibodies in CSF were detected. ICV idursulfase beta demonstrated sustained CSF HS reduction with no new safety signals. Earlier treatment initiation (≤3 years) was associated with improved neurodevelopmental outcomes, regardless of mutation type.