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

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.

Download Full-text

Effects of Exercise Training on Functional Capacity and Quality of Life in a Patient with Late-Onset Pompe Disease Receiving Enzyme Replacement Therapy

Journal of Neuromuscular Diseases ◽

10.3233/jnd-159030 ◽

2015 ◽

Vol 2 (s1) ◽

pp. S33-S33

Author(s):

Rosângela M. Silva ◽

Carmen S.C. Mendes ◽

Carolina C. Aranda ◽

Marco A. Curiati ◽

Maret H. Rand ◽

...

Keyword(s):

Quality Of Life ◽

Exercise Training ◽

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Functional Capacity ◽

Pompe Disease ◽

Late Onset ◽

Enzyme Replacement

Download Full-text

Clinical efficacy of the enzyme replacement therapy in patients with late-onset Pompe disease: a systematic review and a meta-analysis

Journal of Neurology ◽

10.1007/s00415-021-10526-5 ◽

2021 ◽

Author(s):

Berli Sarah ◽

Brandi Giovanna ◽

Keller Emanuela ◽

Najia Nadi ◽

Vitale Josè ◽

...

Keyword(s):

Muscle Strength ◽

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pompe Disease ◽

Late Onset ◽

Meta Analysis ◽

Small Sample ◽

Walking Distance ◽

Enzyme Replacement ◽

Muscle Testing

AbstractIn patients with late-onset Pompe disease (LOPD), the efficacy of the enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) is difficult to evaluate, due to the clinical heterogeneity and the small sample sizes in published studies. Therefore, we conduct a systematic literature review and meta-analysis of the literature to evaluate the efficacy of ERT in LOPD patients considering the walking distance, respiratory function and muscle strength. Particularly, six-minute walk test (6MWT), forced vital capacity (FVC), medical research council (MRC) grading, quantitative muscle testing (QMT), and quick motor function test (QMFT) were outcomes of interest. Overall, 619 studies were identified in PubMed, EMBASE and by manual search on July 18th, 2020. After an initial assessment, 16 studies were included in the meta-analysis, containing clinical data from 589 patients with LOPD. For the 6MWT, 419 patients were analyzed. Walking distance improved on average, 32.2 m greater during the observed period (p = 0.0003), compared to the distance at the baseline. The meta-analysis did not show any improvement in FVC and only a tendency towards better muscle strength after treatment with ERT, but the difference was not statistically significant. In conclusion, the available data showed that ERT has a significant beneficial efficacy in the improvement of walking distance in LOPD patients and a non-significant improvement of muscle strength. No improvement in respiratory capacity was found. More prospective and controlled trials are needed to demonstrate a clear clinical benefit of ERT.

Download Full-text