Fabry Disease and the Effectiveness of Enzyme Replacement Therapy (ERT) in Left Ventricular Hypertrophy (LVH) Improvement: A Review and MetaAnalysis

Int J Med Sci. 2022 Jan 1;19(1):126-131. doi: 10.7150/ijms.66448.

PMID: 34975306

Chung-Lin Lee, Shuan-Pei Lin, Dau-Ming Niu

Highlights: This meta-analysis is performed according to previous studies to review the benefit of ERT for LVH improvement in Fabry patients. Based on the currently available data, this meta-analysis showed that there are beneficial effects on LVH improvement with ERT in Fabry disease patients.

Abstract

Background: Fabry disease is a lysosomal storage disorder that affects many organs and can lead to problems such as cardiomyopathy and left ventricular hypertrophy (LVH). Since 2001, enzyme replacement therapy (ERT) has been the standard of care for Fabry patients. The indications for ERT, on the other hand, are not well defined. To examine the benefit of ERT for LVH improvement in Fabry patients, we conducted a meta-analysis based on prior studies.

Methods: For systematic review purposes, we conducted a literature search in the National Center for Biotechnology Information (NCBI) and PubMed databases without regard to years. Using a pooled analysis of proportions, we conducted a comprehensive evaluation of clinical cohort studies and trials. For both the ERT treatment and ERT treatment-naive groups, we estimated the pooled proportions and confidence intervals (CI) for left ventricular mass index (LVMI). The findings for both before and after ERT treatment are also looked into.

Results: The inclusion criteria were met by 5 cohort studies and 2 randomized controlled trials (RCTs) comprising a total of 552 participants (267 on ERT treatment versus 285 on naive treatment). The difference in LVMI means between the ERT treatment group and the ERT treatment-naive group was -0.149 [95% CI: - 0.431, 0.132] according to the pooled proportions analysis. The ERT treatment group outperformed the ERT treatment-naive group in terms of effect differences (p = 0.034). Three cohort studies and one randomized controlled trial (RCT) with a total of 442 participants were included in another analysis (228 on before ERT and 214 on 4 years after ERT). The difference in LVMI means between the before and after ERT treatment groups was -0.448 [95% CI: -0.787, -0.108] according to the pooled proportions analysis. It favored the 4 years after ERT group (p = 0.037) over the before ERT group.

Conclusion: Our meta-analysis found that ERT has beneficial impacts on LVH improvement in Fabry disease patients based on currently available data. It is preferable to begin ERT as soon as female carriers and atypically affected males have been diagnosed. The role of ERT in LVH improvement has to be investigated further.

Keywords: Enzyme replacement therapy, Fabry disease, Left ventricular hypertrophy, Meta-analysis