Safety and efficacy of idursulfase in the treatment of mucopolysaccharidosis II (Hunter syndrome): a post-marketing study in Japan

Enzyme replacement therapy with idursulfase has been shown to improve somatic signs and symptoms of mucopolysaccharidosis type II (MPS II). Idursulfase is available in Japan (since 2007), based on the outcome of clinical trials conducted in the United States, but data from Japanese patients are limited. This was a postmarketing study of Japanese MPS II patients treated with 0.5 mg/kg intravenous idursulfase weekly, conducted over a period of 8 years after initial administration. Assessments included the safety profile, survival rate, degree of clinical improvement, change in urinary uronic acid (UA) concentration, and 6-minute walk test (6MWT). The safety and efficacy analysis populations included 145 and 143 patients, respectively. The incidence of serious adverse events was 42.8% and the incidence of adverse drug reactions was 48.3%. The 7-year survival rate was 82.7%. Improvements in the clinical features of hepatosplenomegaly, skin, joint, and respiratory disorders were reported (per investigator’s assessment). The mean change in urinary UA concentration was −128.39 mg/g creatinine, and that of 6MWT walking distance was +31.8 m. Long-term idursulfase treatment was well tolerated, and effective in improving clinical features, reducing urinary UA, and slowing disease progression in Japanese MPS II patients.

采用艾杜硫酸酶（idursulfase）的酶替代疗法（Enzyme replacement therapy）已被证实可改善黏多糖贮积症II型（mucopolysaccharidosis type II, MPS II）患者的躯体体征与临床症状。基于美国开展的临床试验结果，艾杜硫酸酶已于2007年在日本获批上市，但日本患者的相关临床数据仍较为有限。本研究为一项针对日本MPS II患者的上市后研究，受试者每周接受0.5 mg/kg剂量的静脉输注型艾杜硫酸酶治疗，初始给药后随访周期共计8年。本次评估指标涵盖安全性概况、生存率、临床改善程度、尿糖醛酸（urinary uronic acid, UA）浓度变化以及6分钟步行试验（6-minute walk test, 6MWT）结果。安全性分析队列与有效性分析队列分别纳入145例与143例患者。严重不良事件（serious adverse events）发生率达42.8%，药品不良反应（adverse drug reactions）发生率为48.3%。7年生存率为82.7%。经研究者评估确认，肝脾肿大（hepatosplenomegaly）、皮肤、关节及呼吸系统病症相关的临床特征均得到改善。尿糖醛酸浓度的平均变化值为-128.39 mg/g肌酐，6MWT步行距离的平均变化值为+31.8米。长期艾杜硫酸酶治疗耐受性良好，可有效改善日本MPS II患者的临床特征、降低尿糖醛酸水平并延缓疾病进展。