Giugliani Roberto, Hwu Wuh-Liang, Tylki-Szymanska Anna, Whiteman David A H, Pano Arian
1] Department of Genetics, Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil [2] National Institute of Medical Genetics Population (INAGEMP), Porto Alegre, Brazil.
Department of Pediatrics and Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
Genet Med. 2014 Jun;16(6):435-41. doi: 10.1038/gim.2013.162. Epub 2013 Nov 7.
The primary objective of this study was to determine the safety of idursulfase in Hunter syndrome patients aged 5 years or younger.
Idursulfase (0.5 mg/kg) was administered intravenously on a weekly basis (52 infusions per patient) in an open-label study. Safety monitoring included adverse events, anti-idursulfase antibodies, vital signs, physical examination, 12-lead electrocardiogram, concomitant medications or procedures, and laboratory testing (clinical chemistry, hematology, and urinalysis). The following exploratory efficacy outcomes were assessed at baseline and at weeks 18 or 36 or 53: urinary glycosaminoglycan levels, liver or spleen size, developmental milestones, and growth indices. Pharmacokinetic parameters were assessed at week 27.
Twenty-eight boys aged 1.4-7.5 years were enrolled (one discontinued for noncompliance) in the study. All the patients reported adverse events (16 patients (57%) reported possibly or probably treatment-related adverse events). The only severe adverse event was sleep apnea (two patients); others were mild or moderate. Sixteen patients had infusion-related adverse events, a similar proportion as previously reported. Thirteen patients (46%) experienced at least one serious adverse event: pyrexia and bronchopneumonia were the most common (three patients each). No clinically important drug-related changes in laboratory parameters or vital signs or electrocardiograms were reported. Nineteen patients (68%) developed anti-idursulfase immunoglobulin G antibodies. Growth rates remained within normal age-related ranges. Developmental quotients were lower than normal but remained stable. By week 18, organ size and urinary glycosaminoglycan levels decreased as compared with baseline and remained stable throughout the study.
Idursulfase safety, tolerability, and efficacy were similar to that previously reported in males ≥5 years.
本研究的主要目的是确定艾度硫酸酯酶在5岁及以下亨特综合征患者中的安全性。
在一项开放标签研究中，每周静脉注射艾度硫酸酯酶（0.5mg/kg）（每位患者52次输注）。安全性监测包括不良事件、抗艾度硫酸酯酶抗体、生命体征、体格检查、12导联心电图、伴随用药或操作以及实验室检测（临床化学、血液学和尿液分析）。在基线以及第18、36或53周评估以下探索性疗效指标：尿糖胺聚糖水平、肝脏或脾脏大小、发育里程碑和生长指数。在第27周评估药代动力学参数。
28名年龄在1.4至7.5岁的男孩被纳入研究（1名因不依从退出）。所有患者均报告了不良事件（16名患者（57%）报告了可能或很可能与治疗相关的不良事件）。唯一的严重不良事件是睡眠呼吸暂停（2名患者）；其他为轻度或中度。16名患者出现输注相关不良事件，比例与先前报告相似。13名患者（46%）经历了至少一次严重不良事件：发热和支气管肺炎最常见（各3名患者）。未报告实验室参数、生命体征或心电图有临床重要的药物相关变化。19名患者（68%）产生了抗艾度硫酸酯酶免疫球蛋白G抗体。生长速率保持在与年龄相关的正常范围内。发育商低于正常但保持稳定。到第18周时，与基线相比，器官大小和尿糖胺聚糖水平下降，并在整个研究过程中保持稳定。
艾度硫酸酯酶的安全性、耐受性和疗效与先前在≥5岁男性中报告的相似。
