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. 2025 Aug 21;20(1):451.
doi: 10.1186/s13023-025-03981-0.

Enzyme replacement therapy for the treatment of late onset Pompe disease: A systematic review and network meta-analysis

Mark Corbett  1 , Chinyereugo Umemneku-Chikere  1 , Sarah Nevitt  1 , Nyanar Jasmine Deng  1 , Matthew Walton  1 , Helen Fulbright  1 , Chong Yew Tan  2 , Robin Lachmann  3 , Rachel Churchill  1 , Robert Hodgson  4
Affiliations

Enzyme replacement therapy for the treatment of late onset Pompe disease: A systematic review and network meta-analysis

Mark Corbett et al. Orphanet J Rare Dis. .

Abstract

Background: Late-onset Pompe disease (LOPD) is a rare inherited genetic condition caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. LOPD causes progressive muscle dysfunction and damage, leading to significant morbidity and early mortality. Enzyme replacement therapy (ERT) is the primary treatment for Pompe disease.

Methods: A systematic review and network meta-analysis of published evidence on the clinical effectiveness of ERT and best supportive care (BSC) was undertaken to establish the relative effectiveness of ERT compared to BSC (in the absence of ERT). Bibliographic databases were searched to identify randomised controlled trials (RCTs) or any other prospective ERT studies in patients with Pompe disease. Network meta-analyses (NMA) of RCTs were undertaken to estimate indirect treatment effects for forced vital capacity (FVC) % predicted and the 6-minute walk test (6MWD). A narrative synthesis was employed to summarise other studies.

Results: A total of 38 studies were included in the review. They comprised three RCTs, three RCT extension studies, seven registry studies and 25 single-group prospective studies. The results of two RCTs were judged to have a high risk of bias. In the NMA, after approximately one year, ERT-naïve patients showed significant 6MWD improvements vs. placebo: ~25 m with alglucosidase alfa and ~ 54 m with avalglucosidase alfa. No significant differences were found for FVC % predicted or comparisons with cipaglucosidase alfa, although very few ERT-naïve patients taking cipaglucosidase alfa were available for the analyses. Intra-ERT comparisons showed a significant 6MWD advantage for avalglucosidase alfa. However, a sensitivity analysis adjusting for skewed data revealed no significant differences. Long-term ERT effectiveness was assessed in single-group studies, showing initial gains maintained for 1-3 years, followed by gradual 10-15-year declines in 6MWD and FVC % predicted. However, small sample sizes and missing data introduce uncertainty.

Conclusions: Our NMA results showed that ERTs lead to modest improvements in 6MWD after 1 year compared to placebo in ERT-naive populations. However, there is limited evidence supporting meaningful differences in outcomes between ERTs. There is a lack of longer-term follow-up data supporting the effectiveness of ERTs compared to each other and to best supportive care.

Keywords: Enzyme replacement therapy; Glycogen storage disease type II; Humans; Network Meta-Analysis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests. Clinical trial registration: Not applicable.

Figures

Fig. 1
Fig. 1
Indirect comparison network
Fig. 2
Fig. 2
PRISMA flow chart
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References

    1. National Institutes of Health. Pompe disease. NIH; n.d. [13 December 2023)]; Available from: https://www.ninds.nih.gov/health-information/disorders/pompe-disease
    1. n der Ploeg A, Carlier PG, Carlier RY, Kissel JT, Schoser B, Wenninger S et al. Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study. Molecular Genetics & Metabolism. [Clinical Trial, Phase IV Multicenter Study Research Support, Non-U.S. Gov’t]. 2016 09;119(1–2):115 – 23. - PubMed
    1. n der Ploeg AT, Clemens PR, Corzo D, Escolar DM, Florence J, Groeneveld GJ et al. A randomized study of alglucosidase alfa in late-onset Pompe’s disease. N Engl J Med. [Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2010;362(15):1396 – 406. - PubMed
    1. n der Ploeg AT, Reuser AJ. Pompe’s disease. Lancet [Review]. 2008;372(9646):1342–53. - PubMed
    1. n der Ploeg AT, Kruijshaar ME, Toscano A, Laforet P, Angelini C, Lachmann RH et al. European consensus for starting and stopping enzyme replacement therapy in adult patients with Pompe disease: a 10-year experience. Eur J Neurol. [Review Systematic Review]. 2017 06;24(6):768-e31. - PubMed

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