1. Department of Pediatrics, MacKay Memorial Hospital, Taipei, Taiwan.
2. Institute of Clinical Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan.
3. Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.
4. MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan.
5. Department of Rare Disease Center, MacKay Memorial Hospital, Taipei, Taiwan.
6. Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
7. Department of Infant and Child Care, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.
8. Taiwan Clinical Trial Consortium in Fabry Disease.
9. Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
10. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Background: Fabry disease is an inherited lysosomal storage disease affecting multiple organs with complications, including cardiomyopathy such as left ventricular hypertrophy (LVH). Enzyme replacement therapy (ERT) has been the main treatment for Fabry patients since 2001. However, the indications of ERT are not clearly defined. We performed a meta-analysis according to previous studies to review the benefit of ERT for LVH improvement in Fabry patients.
Methods: We performed a literature search from the National Center for Biotechnology Information (NCBI) and PubMed database without restriction of years for systematic review purposes. We performed a systematic review of clinical cohort studies and trials using a pooled analysis of proportions. We calculated the pooled proportions and the confidence intervals (CI) for left ventricular mass index (LVMI) for both ERT treatment and ERT treatment-naïve groups. The results for before ERT treatment and after ERT treatment are also investigated.
Results: A total of 5 cohort studies and 2 randomized controlled trials (RCTs), involving a total of 552 participants (267 on ERT treatment versus 285 on naïve treatment), met the inclusion criteria. The pooled proportions analysis showed that the difference in means of LVMI between the ERT treatment group and the ERT treatment-naïve group was -0.149 [95% CI: -0.431, 0.132]. Effect differences favored the ERT treatment group over the ERT treatment-naïve group (p = 0.034). Another analysis included 3 cohort studies and 1 RCT with 442 participants (228 on before ERT and 214 on 4 years after ERT). The pooled proportions analysis showed that the difference in means of LVMI between the before ERT treatment group and the after ERT treatment group was -0.448 [95% CI: -0.787, -0.108]. It favored the 4 years after ERT group over the before ERT group (p = 0.037).
Conclusions: Based on the currently available data, our meta-analysis showed that there are beneficial effects on LVH improvement with ERT in Fabry disease patients. It is better to start ERT as soon as we have diagnoses in female carriers and atypically affected males. Further research is needed to investigate the role of ERT in LVH improvement.
Keywords: Enzyme replacement therapy, Fabry disease, Left ventricular hypertrophy, Meta-analysis