Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Medical Genetics Service/HCPA, Department of Genetics/UFRGS and INAGEMP, Porto Alegre, Brazil.
Orphanet J Rare Dis. 2017 Oct 3;12(1):161. doi: 10.1186/s13023-017-0712-3.
Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare, X-linked disorder caused by deficient activity of the enzyme iduronate-2-sulfatase (I2S). Treatment is available in the form of enzyme replacement therapy (ERT) with recombinant I2S. Clinical outcomes following ≥3 years of ERT with idursulfase were investigated in a broad population of patients with MPS II enrolled in the Hunter Outcome Survey (HOS).
As of January 2016, 639 patients (excluding female patients, individuals who had received a bone marrow transplant and those enrolled in the phase 1/2 [TKT018] or phase 2/3 [TKT024] clinical trial) followed prospectively in the registry had received idursulfase for ≥6 months. These individuals all had data available for ≥1 clinical parameter at baseline and ≥1 additional time point following treatment initiation. Changes in clinical parameters were assessed in the subcohorts of patients with a measurement at baseline and at year 1, 2 or 3 of treatment. Safety data from patients who started treatment at or after enrollment in HOS (n = 233) were also assessed.
Median (10th, 90th percentiles) age at first treatment was 6.2 (2.1, 18.2) years and median treatment duration was 56.3 (18.2, 97.6) months. Urinary glycosaminoglycan (uGAG) levels decreased from baseline to year 3 in patients with data available at this time point (median change from baseline: -201.0 [-591.4, -21.9] μg/mg creatinine [n = 121]). Improvements in the following parameters were observed at year 3 in the subcohorts: 6-min walking test (6MWT) distance, 10.6 (-33.6, 50.8)% (n = 26); left ventricular mass index (LVMI), -9.3 (-31.5, 19.7)% (n = 52); absolute forced vital capacity (FVC), 29.7 (-13.4, 66.7)% (n = 23); absolute forced expiratory volume in 1 s (FEV), 22.8 (-15.2, 62.1)% (n = 22); palpable liver size, -54.5 (-85.7, 50.0)% (n = 53); palpable spleen size, -33.3 (-80.0, 33.3)% (n = 17). No new or unexpected safety concerns were identified in this analysis.
These findings suggest that idursulfase has a positive effect on uGAG levels, 6MWT results, LVMI, FVC, FEV and hepatosplenomegaly after 1, 2 and 3 years treatment.
黏多糖贮积症 II 型（MPS II；亨特综合征）是一种罕见的 X 连锁疾病，由艾杜糖-2-硫酸酯酶（I2S）缺乏活性引起。治疗方法为采用重组 I2S 进行酶替代疗法（ERT）。在 Hunter Outcome Survey（HOS）中，对接受伊杜磺酸钠 ERT 治疗至少 3 年的广泛 MPS II 患者的临床结局进行了调查。
截至 2016 年 1 月，639 例（不包括女性患者、接受过骨髓移植的患者和参加过 TKT018 期/2 期或 TKT024 期/3 期临床试验的患者）患者在登记处进行前瞻性随访，他们接受伊杜磺酸钠治疗时间超过 6 个月。这些患者在基线和治疗开始后至少 1 个额外时间点都有至少 1 个临床参数的数据。在基线和治疗 1、2 或 3 年有测量值的患者亚组中评估了临床参数的变化。还评估了在 HOS 登记时或之后开始治疗的患者（n=233）的安全性数据。
首次治疗时的中位（第 10 百分位数、第 90 百分位数）年龄为 6.2（2.1，18.2）岁，中位治疗时间为 56.3（18.2，97.6）个月。在该时间点有数据的患者中，尿糖胺聚糖（uGAG）水平从基线下降到第 3 年（从基线的中位数变化：-201.0[-591.4，-21.9]μg/mg 肌酐[n=121]）。在亚组中，在第 3 年观察到以下参数的改善：6 分钟步行试验（6MWT）距离，10.6[-33.6，50.8]%（n=26）；左心室质量指数（LVMI），-9.3[-31.5，19.7]%（n=52）；绝对用力肺活量（FVC），29.7[-13.4，66.7]%（n=23）；绝对 1 秒用力呼气量（FEV），22.8[-15.2，62.1]%（n=22）；可触及的肝大小，-54.5[-85.7，50.0]%（n=53）；可触及的脾大小，-33.3[-80.0，33.3]%（n=17）。在本次分析中，未发现新的或意外的安全性问题。
这些发现表明，伊杜磺酸钠治疗 1、2 和 3 年后，对 uGAG 水平、6MWT 结果、LVMI、FVC、FEV 和肝脾肿大有积极影响。
