Journal of Neurology

, Volume 264, Issue 4, pp 621–630 | Cite as

Survival and long-term outcomes in late-onset Pompe disease following alglucosidase alfa treatment: a systematic review and meta-analysis

  • Benedikt Schoser
  • Andrew Stewart
  • Steve Kanters
  • Alaa Hamed
  • Jeroen Jansen
  • Keith Chan
  • Mohammad Karamouzian
  • Antonio Toscano


A number of studies have assessed the efficacy of alglucosidase alfa as an enzyme replacement therapy (ERT) on motor and respiratory endpoints in patients with late-onset Pompe disease (LOPD). A previous review evaluated the clinical efficacy and safety of alglucosidase alfa; however, it is difficult to draw inferences from individual studies due to small patient populations, particularly in evaluating the benefit on survival. To evaluate the current evidence on the long-term efficacy of alglucosidase alfa with regard to survival, motor, and respiratory function in patients with LOPD in relation to the natural progression of the disease, a new systematic literature review was performed identifying studies that assessed either mortality, percent predicted forced vital capacity (% FVC), or the 6-min walk test (6MWT) among treated and untreated LOPD patients. Patient overlap was avoided by removing smaller studies or ensuring the use of only one conflicting study per outcome. Mortality was modeled using Poisson models for each treatment group. Outcomes were modeled using first- and second-order fractional polynomial meta-analysis with fixed- and random-effects. Meta-regression was used to explore sources of heterogeneity. Twenty-two publications pertaining to 19 studies/trials were selected, including 438 patients when accounting for overlaps, with the average study duration being 45.7 months. Patients treated with alglucosidase alfa in these studies had a nearly five-fold lower mortality rate than untreated patients (rate ratio: 0.21; 95 % credible interval: 0.11, 0.41). On average, % FVC declined consistently among untreated patients, including a 2.3 % decline after 12 months follow-up and 6.2 % decline after 48 months. This is in contrast to alglucosidase alfa-treated patients, who, on average, improved rapidly, with an increase of 1.4 % FVC after 2 months, followed by a slow regression back to baseline over a three-year period. Nonetheless, the relative difference between those treated and not grew over time, from 4.5 % FVC after 12 months to 6 % FVC after 48 months. In the 6MWT, alglucosidase alfa-treated patients on average had the largest improvement over the first 20 months of treatment of approximately 50 meters increase over baseline, with its substantial stabilization in the following years. By comparison, untreated patients do not show 6MWT improvement over time. Alglucosidase alfa has a beneficial effect in LOPD patients as demonstrated by improvements in survival and ambulation maintained over time, as well as prevention of deterioration in respiratory function.


Late-onset Pompe disease (LOPD)  Glycogen storage disease type 2  Enzyme replacement therapy  Alglucosidase alfa  Systematic review 


Compliance with ethical standards

Conflict of interest

BS has received research support, honoraria, and travel funding from Sanofi Genzyme during the past 5 years. Dr. Schoser is member of the Genzyme Pompe Disease Global Advisory Board. Dr. Schoser received honoraria and travel funding as member of the Global Advisory Boards from Biomarin Pharmaceutical, Amicus Therapeutics, and Audentes Therapeutics. AS is an employee of Sanofi Genzyme and stockholder of Sanofi. SK is an employee of Redwood Outcomes, a research consulting firm owned by Precision for Medicine and, holds no Sanofi stock. AH is an employee of Sanofi Genzyme and stockholder of Sanofi. JJ is an employee of Redwood Outcomes, a research consulting firm owned by Precision for Medicine and, holds no Sanofi stock. KC is an employee of Redwood Outcomes, a research consulting firm owned by Precision for Medicine, and holds no Sanofi stock. MK was an employee of Redwood Outcomes, a research consulting firm owned by Precision for Medicine, and holds no Sanofi stock. In the last 5 years, AT has received, from Sanofi Genzyme, travel grants and honoraria for teaching courses, lectures and, being also a member of the Genzyme Pompe Disease Global Advisory Board for his participation to the related meetings. Prof. Toscano has also received travel grants and honoraria from Biomarin Pharmaceuticals for his participation to the Biomarin Pompe Advisory Board meetings.

Supplementary material

415_2016_8219_MOESM1_ESM.docx (638 kb)
Supplementary material 1 (DOCX 639 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Friedrich-Baur-Institut, Neurologische Klinik, Klinikum der Universität MünchenMunichGermany
  2. 2.Sanofi Genzyme, Patient Outcomes and Medical EconomicsCambridgeUSA
  3. 3.School of Population and Public HealthUniversity of British ColumbiaVancouverCanada
  4. 4.Redwood OutcomesVancouverCanada
  5. 5.Department of Clinical and Experimental Medicine, Reference Center for Rare Neuromuscular DisordersUniversity of MessinaMessinaItaly

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