Frontiers in Pediatrics (Feb 2024)
Efficacy and safety of enzyme replacement therapy with alglucosidase alfa for the treatment of patients with infantile-onset Pompe disease: a systematic review and metanalysis
Abstract
IntroductionPompe disease (PD) is a glycogen disorder caused by the 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 infantile-onset PD (IOPD).MethodsWe systematically searched the MEDLINE (via PubMed) and Embase databases for prospective clinical studies evaluating ERT for IOPD on pre-specified outcomes. Meta-analysis was also performed.ResultsOf 1,722 articles identified, 16 were included, evaluating 316 patients. Studies were heterogeneous and with very low certainty of evidence for most outcomes. A moderate/high risk of bias was present for most included articles. The following outcomes showed improvements associated with alglucosidase alfa, over natural history of PD/placebo, for a mean follow-up of 48.3 months: left ventricular (LV) mass {mean change 131.3 g/m2 [95% confidence interval (CI) 81.02, 181.59]}, time to start ventilation (TSV) [HR 0.21 (95% CI: 0.12, 0.36)], and survival [HR 0.10 (95% CI: 0.05, 0.19)]. There were no differences between the pre- and post-ERT period for myocardial function and psychomotor development. Adverse events (AEs) after ERT were mild in most cases.ConclusionOur data suggest that alglucosidase alfa potentially improves LV mass, TSV, and survival in IOPD patients, with no important safety issues.Systematic Review RegistrationPROSPERO identifier (CRD42019123700).
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