Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Oct 21;10(21):4828.
doi: 10.3390/jcm10214828.

A Systematic Review and Meta-Analysis of Enzyme Replacement Therapy in Late-Onset Pompe Disease

Alícia Dorneles Dornelles  1   2 , Ana Paula Pedroso Junges  2   3 , Tiago Veiga Pereira  4   5 , Bárbara Corrêa Krug  6 , Candice Beatriz Treter Gonçalves  6 , Juan Clinton Llerena Jr  7 , Priya Sunil Kishnani  8 , Haliton Alves de Oliveira Jr  9 , Ida Vanessa Doederlein Schwartz  1   2   3   6   10
Affiliations
Review

A Systematic Review and Meta-Analysis of Enzyme Replacement Therapy in Late-Onset Pompe Disease

Alícia Dorneles Dornelles et al. J Clin Med. .

Abstract

Pompe disease (PD) is a glycogen storage disorder caused by 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 late-onset PD (LOPD).

Methods: We systematically searched the MEDLINE (via PubMed), Embase, and Cochrane databases for prospective clinical studies evaluating ERT for LOPD on pre-specified outcomes. A meta-analysis was also performed.

Results: Of 1601 articles identified, 22 were included. Studies were heterogeneous and with very low certainty of evidence for most outcomes. The following outcomes showed improvements associated with GAA ERT, over a mean follow-up of 32.5 months: distance walked in the 6-min walking test (6MWT) (mean change 35.7 m (95% confidence interval [CI] 7.78, 63.75)), physical domain of the SF-36 quality of life (QOL) questionnaire (mean change 1.96 (95% CI 0.33, 3.59)), and time on ventilation (TOV) (mean change -2.64 h (95% CI -5.28, 0.00)). There were no differences between the pre- and post-ERT period for functional vital capacity (FVC), Walton and Gardner-Medwin Scale score, upper-limb strength, or total SF-36 QOL score. Adverse events (AEs) after ERT were mild in most cases.

Conclusion: Considering the limitations imposed by the rarity of PD, our data suggest that GAA ERT improves 6MWT, physical QOL, and TOV in LOPD patients. ERT was safe in the studied population. PROSPERO register: 135102.

Keywords: Pompe disease; alpha-glucosidase; enzyme replacement therapy; glycogen storage disease type II.

PubMed Disclaimer

Conflict of interest statement

P.S.K. has received research/grant support from Sanofi Genzyme, Valerion Therapeutics, Shire Pharmaceuticals, and Amicus Therapeutics. P.S.K. has received consulting fees and honoraria from Sanofi Genzyme, Shire Pharmaceuticals, Amicus Therapeutics, Vertex Pharmaceuticals, Maze Therapeutics, JCR Pharmaceutical and Asklepios BioPharmaceuticalBiopharmaceutical, Inc. (AskBio). P.S.K. is a member of the Pompe and Gaucher Disease Registry Advisory Board for Sanofi Genzyme., Amicus Therapeutics, and Baebies. P.S.K. has equity in Asklepios Biopharmaceutical, Inc. (AskBio), which is developing gene therapy for Pompe disease and Maze Therapeutics, which is developing small molecule in Pompe disease. All other authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
PRISMA flow diagram of search results.
Figure 2
Figure 2
Evaluation of forced vital capacity (% of predicted) in upright position in patients with late-onset Pompe disease on enzyme replacement therapy with alglucosidase alfa. Weights are inverse-variance weights and are proportional to the contribution of each study to the summary estimate. I2 is the fraction of variance that is due to statistical heterogeneity and not chance. Tau2 denotes the between-study variance.
Figure 3
Figure 3
Evaluation of 6-min walking test performance (distance walked in meters) in patients with late-onset Pompe disease on enzyme replacement therapy with alglucosidase alfa. Weights are inverse-variance weights and are proportional to the contribution of each study to the summary estimate. I2 is the fraction of variance that is due to statistical heterogeneity and not chance. Tau2 denotes the between-study variance.
Figure 4
Figure 4
Evaluation of handheld dynamometry in patients with late-onset Pompe disease on enzyme replacement therapy with alglucosidase alfa. Weights are inverse-variance weights and are proportional to the contribution of each study to the summary estimate. I2 is the fraction of variance that is due to statistical heterogeneity and not chance. Tau2 denotes the between-study variance.
Figure 5
Figure 5
Evaluation of the Quick Motor Function Test in patients with late-onset Pompe disease on enzyme replacement therapy with alglucosidase alfa. Weights are inverse-variance weights and are proportional to the contribution of each study to the summary estimate. I2 is the fraction of variance that is due to statistical heterogeneity and not chance. Tau2 denotes the between-study variance.
Figure 6
Figure 6
Evaluation of the quality of life of patients with late-onset Pompe disease on enzyme replacement therapy with alglucosidase alfa. Weights are inverse-variance weights and are proportional to the contribution of each study to the summary estimate. I2 is the fraction of variance that is due to statistical heterogeneity and not chance. Tau2 denotes the between-study variance.
Figure 7
Figure 7
Evaluation of the time on ventilation (h) of patients with late-onset Pompe disease on enzyme replacement therapy with alglucosidase alfa. Weights are inverse-variance weights and are proportional to the contribution of each study to the summary estimate. I2 is the fraction of variance that is due to statistical heterogeneity and not chance. Tau2 denotes the between-study variance.
Figure 8
Figure 8
Risk of bias of included studies evaluated through the ROBIN-I tool.
See this image and copyright information in PMC

References

    1. Llerena J.C., Horovitz D.M., Marie S.K., Porta G., Giugliani R., Rojas M.V., Martins A.M., Brazilian Network for Studies in Pompe Disease (ReBrPOM) The Brazilian consensus on the management of Pompe disease. J. Pediatr. 2009;155:S47–S56. doi: 10.1016/j.jpeds.2009.07.006. - DOI - PubMed
    1. Levine J.C., Kishnani P.S., Chen Y.T., Herlong J.R., Li J.S. Cardiac remodeling after enzyme replacement therapy with acid alpha-glucosidase for infants with Pompe disease. Pediatr. Cardiol. 2008;29:1033–1042. doi: 10.1007/s00246-008-9267-3. - DOI - PMC - PubMed
    1. Slonim A.E., Bulone L., Goldberg T., Minikes J., Slonim E., Galanko J., Martiniuk F. Modification of the natural history of adult-onset acid maltase deficiency by nutrition and exercise therapy. Muscle Nerve. 2007;35:70–77. doi: 10.1002/mus.20665. - DOI - PubMed
    1. Geel T.M., McLaughlin P.M., de Leij L.F., Ruiters M.H., Niezen-Koning K.E. Pompe disease: Current state of treatment modalities and animal models. Mol. Genet. Metab. 2007;92:299–307. doi: 10.1016/j.ymgme.2007.07.009. - DOI - PubMed
    1. Winchester B., Bali D., Bodamer O.A., Caillaud C., Christensen E., Cooper A., Cupler E., Deschauer M., Fumić K., Jackson M., et al. Methods for a prompt and reliable laboratory diagnosis of Pompe disease: Report from an international consensus meeting. Mol. Genet. Metab. 2008;93:275–281. doi: 10.1016/j.ymgme.2007.09.006. - DOI - PubMed

LinkOut - more resources