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

  • Front Pediatr. 2024 Feb 15:12:1310317. doi: 10.3389/fped.2024.1310317.
A D Dornelles  1  2  1 ,  A P P Junges  3 ,  B Krug  4 ,  C Gonçalves  4 ,  H A de Oliveira Junior  5 ,  I V D Schwartz  1  3  4  6
Affiliations
  • 1. Faculty of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
  • 2. Pediatric Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
  • 3. Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
  • 4. Nuclimed, Clinical Research Centre, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
  • 5. Health Technology Assessment Unit, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.
  • 6. Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
PMID: 38425665 DOI: 10.3389/fped.2024.1310317
Abstract

Introduction: Pompe 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).

Methods: We 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.

Results: Of 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.

Conclusion: Our data suggest that alglucosidase alfa potentially improves LV mass, TSV, and survival in IOPD patients, with no important safety issues.

Systematic review registration: PROSPERO identifier (CRD42019123700).

Keywords
Pompe disease; alglucosidase alfa; enzyme replacement therapy; glycogen storage disease type II; meta-analysis; systematic review.
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