Elliott Perry M, Germain Dominique P, Hilz Max J, Spada Marco, Wanner Christoph, Falissard Bruno
University College London and Barts Heart Centre, London, United Kingdom.
French Referral Center for Fabry disease, Division of Medical Genetics and INSERM U1179, University of Versailles, Paris-Saclay University, Montigny, France.
Eur J Med Genet. 2019 Oct;62(10):103702. doi: 10.1016/j.ejmg.2019.103702. Epub 2019 Jun 10.
Fabry disease is an X-linked inherited, progressive disorder of lipid metabolism resulting from the deficient activity of the enzyme α-galactosidase. Enzyme replacement therapy (ERT) with recombinant agalsidase, with intravenous infusions of either agalsidase beta or agalsidase alfa, is available and clinical experience now exceeds 15 years. There are very few randomised, placebo-controlled clinical trials evaluating the outcomes of ERT. Data are often derived from observational, registry-based studies and case reports. Pooled analysis of data from different sources may be limited by the heterogeneity of the patient populations, outcomes and treatment. Therefore, comprehensive systematic literature reviews of unpooled data are needed to determine the effects of ERT on disease outcomes. A systematic literature search was conducted in the Embase and PubMed (MEDLINE) databases to retrieve original articles that evaluated outcomes of ERT in patients with Fabry disease; the outcome data were analysed unpooled. The literature analysis included the full range of published literature including observational studies and case series/case reports. Considerable heterogeneity was found among the studies, with differences in sample size, statistical methods, ERT regimens and patient demographic and clinical characteristics. We have demonstrated the value of performing an unpooled systematic literature review of all published evidence of ERT outcomes in Fabry disease, highlighting that in a rare genetic disorder like Fabry disease, which is phenotypically diverse, different patient populations can require different disease management and therapeutic goals depending on age, genotype, and disease severity/level of organ involvement. In addition, these findings are valuable to guide the design and reporting of new clinical studies.
法布里病是一种X连锁遗传性进行性脂质代谢紊乱疾病，由α-半乳糖苷酶活性缺乏所致。目前可采用重组α-半乳糖苷酶进行酶替代疗法（ERT），通过静脉输注阿加糖酶β或阿加糖酶α，临床应用经验已超过15年。评估ERT疗效的随机、安慰剂对照临床试验非常少。数据通常来自观察性、基于登记处的研究和病例报告。对不同来源的数据进行汇总分析可能会受到患者群体、结局和治疗方法异质性的限制。因此，需要对未汇总的数据进行全面系统的文献综述，以确定ERT对疾病结局的影响。我们在Embase和PubMed（MEDLINE）数据库中进行了系统的文献检索，以获取评估法布里病患者ERT疗效的原始文章；对结局数据进行了未汇总分析。文献分析包括所有已发表的文献，包括观察性研究和病例系列/病例报告。研究之间存在相当大的异质性，在样本量、统计方法、ERT方案以及患者人口统计学和临床特征方面存在差异。我们证明了对法布里病ERT结局的所有已发表证据进行未汇总系统文献综述的价值，强调在像法布里病这样表型多样的罕见遗传性疾病中，不同的患者群体可能需要根据年龄、基因型以及疾病严重程度/器官受累程度制定不同的疾病管理和治疗目标。此外，这些发现对于指导新临床研究的设计和报告具有重要价值。
