da Silva Edina M K, Strufaldi Maria Wany Louzada, Andriolo Régis B, Silva Laercio A
Emergency Medicine and Evidence Based Medicine, Universidade Federal de São Paulo, Rua Borges Lagoa 564 cj 64, Vl. Clementino, São Paulo, São Paulo, Brazil, 04038-000.
Cochrane Database Syst Rev. 2014 Jan 8(1):CD008185. doi: 10.1002/14651858.CD008185.pub3.
Mucopolysaccharidosis II, also known as Hunter syndrome, is a rare, X-linked disease caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase, which catalyses a step in the catabolism of glycosaminoglycans. The glycosaminoglycans accumulate within tissues affecting multiple organs and physiologic systems. The clinical manifestations include neurologic involvement, severe airways obstruction, skeletal deformities and cardiomyopathy. The disease has a variable age of onset and variable rate of progression. In those with severe disease, death usually occurs in the second decade of life, whereas those patients with less severe disease may survive into adulthood. Enzyme replacement therapy with intravenous infusions of idursulfase has emerged as a new treatment for mucopolysaccharidosis type II.
To evaluate the effectiveness and safety of enzyme replacement therapy with idursulfase compared to other interventions, placebo or no intervention, for treating mucopolysaccharidosis type II.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register (date of last search 22 July 2013).We also searched EMBASE, PubMed and the Literature Latino-Americana e do Caribe em Ciências da Saúde (LILACS) (date of last search 09 July 2013).
Randomised and quasi-randomised controlled trials of enzyme replacement therapy with idursulfase compared to no intervention, placebo or other options (e.g. behavioral strategies, transplantation).
Two authors independently screened the trials identified, appraised quality of papers and extracted data.
One study (96 patients) met the inclusion criteria, although the primary outcome of this review - z score for height and weight, was not assessed in the study. This trial was considered to be of overall good quality. Following 53 weeks of treatment, patients in the weekly idursulfase 0.5 mg/kg group demonstrated a significant improvement rate compared with placebo for the primary outcome: distance walked in six minutes on the basis of the sum of ranks of change from baseline, mean difference 37.00 (95% confidence interval 6.52 to 67.48). The every-other-week idursulfase 0.5 mg/kg group also showed an improvement, which was not significant compared with placebo, mean difference 23.00 (95% confidence interval -4.49 to 50.49). After 53 weeks, there was no statistical significance difference in per cent predicted forced vital capacity between the three groups and absolute forced vital capacity was significantly increased from baseline in the weekly dosing group compared to placebo, mean difference 0.16 (95% confidence interval CI 0.05 to 0.27). No difference was observed between the every-other-week idursulfase 0.5 mg/kg group and placebo.In addition, liver and spleen volumes and urine glycosaminoglycan excretion were significantly reduced from baseline by both idursulfase dosing regimens. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 31.7% of patients at the end of the study and they were related to a smaller reduction in urine glycosaminoglycan levels.
AUTHORS' CONCLUSIONS: The current evidence is limited. While the randomised clinical trial identified was considered to be of good quality, it failed to describe important outcomes. It has been demonstrated that enzyme replacement therapy with idursulfase is effective in relation to functional capacity (distance walked in six minutes and forced vital capacity), liver and spleen volumes and urine glycosaminoglycan excretion in patients with mucopolysaccharidosis type II compared with placebo. There is no available evidence in the included study and in the literature on outcomes such as improvement in growth, sleep apnoea, cardiac function, quality of life and mortality. More studies are needed to obtain more information on the long-term effectiveness and safety of enzyme replacement therapy.
黏多糖贮积症II型，又称亨特综合征，是一种罕见的X连锁疾病，由溶酶体酶艾杜糖醛酸-2-硫酸酯酶缺乏引起，该酶催化糖胺聚糖分解代谢中的一个步骤。糖胺聚糖在组织内蓄积，影响多个器官和生理系统。临床表现包括神经受累、严重气道阻塞、骨骼畸形和心肌病。该病发病年龄和进展速度各不相同。重症患者通常在生命的第二个十年死亡，而病情较轻的患者可能存活至成年。静脉输注艾杜糖硫酸酯酶进行酶替代治疗已成为黏多糖贮积症II型的一种新疗法。
评估与其他干预措施、安慰剂或不干预相比，艾杜糖硫酸酯酶酶替代治疗黏多糖贮积症II型的有效性和安全性。
我们检索了Cochrane囊性纤维化和遗传疾病组试验注册库（最后检索日期为2013年7月22日）。我们还检索了EMBASE、PubMed和拉丁美洲及加勒比卫生科学文献数据库（LILACS）（最后检索日期为2013年7月9日）。
与不干预、安慰剂或其他选项（如行为策略、移植）相比，艾杜糖硫酸酯酶酶替代治疗的随机和半随机对照试验。
两位作者独立筛选所确定的试验，评估论文质量并提取数据。
一项研究（96例患者）符合纳入标准，尽管该研究未评估本综述的主要结局——身高和体重的z评分。该试验总体质量被认为良好。治疗53周后，每周接受0.5mg/kg艾杜糖硫酸酯酶治疗的患者组在主要结局方面与安慰剂相比有显著改善率：根据自基线变化的秩和计算，6分钟步行距离，平均差异为37.00（95%置信区间为6.52至67.48）。每两周接受0.5mg/kg艾杜糖硫酸酯酶治疗的患者组也有改善，但与安慰剂相比不显著，平均差异为23.00（95%置信区间为-4.49至50.49）。53周后，三组间预测用力肺活量百分比无统计学显著差异，与安慰剂相比，每周给药组的绝对用力肺活量自基线显著增加，平均差异为0.16（95%置信区间为0.05至0.27）。每两周接受0.5mg/kg艾杜糖硫酸酯酶治疗的患者组与安慰剂之间未观察到差异。此外，两种艾杜糖硫酸酯酶给药方案均使肝脏和脾脏体积以及尿糖胺聚糖排泄量自基线显著降低。艾杜糖硫酸酯酶总体耐受性良好，但确实发生了输注反应。在研究结束时，31.7%的患者检测到艾杜糖硫酸酯酶抗体，且它们与尿糖胺聚糖水平降低幅度较小有关。
目前的证据有限。虽然所确定的随机临床试验质量良好，但未能描述重要结局。已证明与安慰剂相比，艾杜糖硫酸酯酶酶替代治疗对黏多糖贮积症II型患者的功能能力（6分钟步行距离和用力肺活量）、肝脏和脾脏体积以及尿糖胺聚糖排泄有效。纳入研究及文献中均无关于生长改善、睡眠呼吸暂停改善、心脏功能、生活质量和死亡率等结局的可用证据。需要更多研究以获取关于酶替代治疗长期有效性和安全性的更多信息。
