Dornelles Alícia Dorneles, Junges Ana Paula Pedroso, Pereira Tiago Veiga, Krug Bárbara Corrêa, Gonçalves Candice Beatriz Treter, Llerena Juan Clinton, Kishnani Priya Sunil, de Oliveira Haliton Alves, Schwartz Ida Vanessa Doederlein
Postgraduate Program in Medical Sciences, Faculty of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre CEP 90035003, Brazil.
Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre CEP 90035903, Brazil.
J Clin Med. 2021 Oct 21;10(21):4828. doi: 10.3390/jcm10214828.
Pompe disease (PD) is a glycogen storage disorder caused by deficient activity of acid alpha-glucosidase (GAA). We sought to review the latest available evidence on the safety and efficacy of recombinant human GAA enzyme replacement therapy (ERT) for late-onset PD (LOPD).
We systematically searched the MEDLINE (via PubMed), Embase, and Cochrane databases for prospective clinical studies evaluating ERT for LOPD on pre-specified outcomes. A meta-analysis was also performed.
Of 1601 articles identified, 22 were included. Studies were heterogeneous and with very low certainty of evidence for most outcomes. The following outcomes showed improvements associated with GAA ERT, over a mean follow-up of 32.5 months: distance walked in the 6-min walking test (6MWT) (mean change 35.7 m (95% confidence interval [CI] 7.78, 63.75)), physical domain of the SF-36 quality of life (QOL) questionnaire (mean change 1.96 (95% CI 0.33, 3.59)), and time on ventilation (TOV) (mean change -2.64 h (95% CI -5.28, 0.00)). There were no differences between the pre- and post-ERT period for functional vital capacity (FVC), Walton and Gardner-Medwin Scale score, upper-limb strength, or total SF-36 QOL score. Adverse events (AEs) after ERT were mild in most cases.
Considering the limitations imposed by the rarity of PD, our data suggest that GAA ERT improves 6MWT, physical QOL, and TOV in LOPD patients. ERT was safe in the studied population. PROSPERO register: 135102.
庞贝病（PD）是一种由酸性α-葡萄糖苷酶（GAA）活性不足引起的糖原贮积病。我们试图回顾关于重组人GAA酶替代疗法（ERT）治疗晚发型庞贝病（LOPD）的安全性和有效性的最新证据。
我们系统检索了MEDLINE（通过PubMed）、Embase和Cochrane数据库，以查找评估ERT治疗LOPD的预先指定结局的前瞻性临床研究。还进行了荟萃分析。
在识别出的1601篇文章中，纳入了22篇。研究具有异质性，大多数结局的证据确定性非常低。在平均32.5个月的随访中，以下结局显示与GAA ERT相关的改善：6分钟步行试验（6MWT）中的步行距离（平均变化35.7米（95%置信区间[CI] 7.78，63.75））、SF-36生活质量（QOL）问卷的身体领域（平均变化1.96（95% CI 0.33，3.59））以及通气时间（TOV）（平均变化-2.64小时（95% CI -5.28，0.00））。ERT前后在功能肺活量（FVC）、沃尔顿和加德纳-梅德温量表评分、上肢力量或总SF-36 QOL评分方面没有差异。ERT后的不良事件（AE）在大多数情况下较轻。
考虑到PD罕见性带来的局限性，我们的数据表明GAA ERT可改善LOPD患者的6MWT、身体QOL和TOV。ERT在研究人群中是安全的。PROSPERO注册号：135102。
