Background

In the last 10 years enzyme replacement therapy (ERT) has become an alternative for the treatment of patients with Hunter disease (HD). Nevertheless, the information regarding efficacy and safety is scarce and mainly based on the pivotal trials. This scarcity is especially evident for adults and severe forms of HD.

Methods

A systematic review of publications in the electronic databases PUBMED, EMBASE and Cochrane Central was undertaken. Clinical trials and observational studies were included. The data about efficacy and security were retrieved and analysed with Review Manager version 5.3.

Results

677 records were found, 559 remaining after the removal of duplicates. By title and abstract review, 427 were excluded. Full reading of the rest was made (122 publications) and 42 were finally included. It was not possible to perform meta-analysis of all the endpoints due to high heterogeneity in the reporting and measuring of variables in each publication. Eight clinical trials were included, 6 with high risk of bias. The quality of the other studies was low in 12%, average in 68% and good in 21%. Main findings were: a reduction in the elimination of glycosaminoglycans (GAG) in urine in all the studies (26/26), decrease in liver and spleen size (18/18), increase of 52.59 m (95% CI, 36, 42–68.76, p < .001) in the 6-min walk test (TM6M), increase in forced vital capacity (FVC) of 9.59% (95% CI 4.77–14.51, p < .001), reduction of the left ventricular mass index of 3.57% (95% CI 1.2–5.93) and reduction in mortality (OR) of 0.44 (0.27–0.71).

Discussion

The data suggests a clear and consistent effect of ERT in HD reducing the accumulation of GAGs in the body, demonstrated by the reduction of its urinary excretion, as well as by the reduction of its deposits (spleen, liver and heart). Likewise, there is an improvement in physical and respiratory function. In addition, a reduction in mortality has been observed. Lack of studies, small size of the samples, and methodological deficiencies are the main limitations to establish definite conclusions.

Conclusions

The data suggests that ERT is effective and safe in the treatment of HD. There is a need to evaluate patient-centred outcomes and the impact on quality of life.

中文翻译：

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酶替代疗法治疗亨特病：叙述性合成和荟萃分析的系统综述。

背景

在过去的十年中，酶替代疗法（ERT）已成为治疗Hunter病（HD）患者的替代方法。然而，关于功效和安全性的信息很少，并且主要基于关键试验。对于成年人和严重形式的HD而言，这种稀缺尤其明显。

方法

对PUBMED，EMBASE和Cochrane Central电子数据库中的出版物进行了系统的审查。包括临床试验和观察性研究。有关有效性和安全性的数据已通过Review Manager 5.3版进行了检索和分析。

结果

共找到677条记录，除去重复项后还剩下559条。通过标题和摘要审查，排除了427个。其余全部读完（122篇出版物），最后包括42篇。由于每个出版物中变量的报告和度量均存在高度异质性，因此无法对所有端点进行荟萃分析。包括八项临床试验，其中六项具有高偏倚风险。其他研究的质量较低，为12％，平均为68​​％，良好为21％。主要发现是：在所有研究中尿液中氨基糖胺聚糖（GAG）的消除减少（26/26），肝脏和脾脏大小减少（18/18），增加52.59 m（95％CI，36、42） –68.76，p 在6分钟步行测试（TM6M）中<<001），强迫肺活量（FVC）增加9.59％（95％CI 4.77–14.51，p <.001），左心室质量指数降低3.57％ （95％CI 1.2–5.93），死亡率（OR）降低0.44（0.27–0.71）。

讨论区

数据表明，ERT在HD中具有明显而一致的作用，可减少机体GAG的积累，这可通过减少尿液排泄以及减少沉积物（脾脏，肝脏和心脏）来证明。同样，身体和呼吸功能也得到改善。另外，已经观察到死亡率降低。缺乏研究，样本量小以及方法学上的不足是确定结论的主要限制。

结论

数据表明，ERT治疗HD既有效又安全。有必要评估以患者为中心的结局及其对生活质量的影响。