Safety and efficacy of migalastat in Fabry's disease treatment with cardiac impact : a systematic review and meta-analysis

Abstract Background Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by a-galactosidase A deficiency, leading to systemic accumulation of globotriaosylceramide (Gb3). Cardiac involvement, including left ventricular hypertrophy (LVH) and myocardial fibrosis, significantly contributes to morbidity and mortality. Migalastat, a pharmacological chaperone, enhances enzyme activity and promotes Gb3 clearance. Objectives Our aim is to evaluate the safety and efficacy of chaperone migalastat drug in the treatment of fabry's disease with cardiac involvement, addressing especially the left ventricular body index (LVMI) and other outcomes, such as renal and cerebrovascular Methods A systematic review and meta-analysis search was conducted in the PubMed, Cochrane, Embase, and ScienceDirect databases to identify relevant trials and cohort studies adhering to the PRISMA established guidelines. The inclusion criteria covered studies that evaluated cardiac measures in patients with Fabry's disease, with a minimum follow-up of twelve months and the maximum of 81 months. The main outcomes analyzed were based on cardiac and renal involvement comparing the migalastat intervention group and the non-migalastat control group. Statistical analysis was performed using R software (version 4.2.3) under the random-effects model to estimate pooled outcomes and assess heterogeneity. Results Eight studies were included in this meta-analysis with a total of 359 patients, the unit of measurement for all outcomes was the mean difference (MD). Four studies evaluated the urinary protein levels, the pooled MD was -91.30 mg (95% CI: -242.09; 59.49), with moderate heterogeneity (I² = 52%, p = 0.10), moreover, the pooled MD for Glomerular Filtration Rate (eGFR) in the follow up time was -2.80 mL/min/1.73m² (95% CI: -7.17; 1.57), with moderate heterogeneity (I² = 29%, p = 0.24), no statistically significant difference was detected. The LVMI was analyzed in male versus female, the pooled MD on this group was -1.87 g/m² (95% CI: -12.45; 8.71), with no heterogeneity (I² = 0%, p = 0.88) and with no statistically significant difference was observed between groups. At least, the other outcome verified was LysoGb3, an extremely important biomarker to evaluate the presence of Fabry disease, the pooled MD was 25.31 nmol/L (95% CI: -36.77; 87.39), with extremely high heterogeneity (I² = 99%, p 0.01). Conclusion Migalastat is not directly associated with the reduction of the analyzed outcomes in patients with Fabry disease. Future randomized controlled trials could achieve statistical significance by increasing the sample size through multicenter studies and by stratifying analyses based on patients characteristics, in addition it is extremely necessary to standardize the outcomes and the follow-up times on all trials.Figure 1 - Forest plots 1 and 2 Figure 2 - Forest plots 3 and 4