Large variation in effects during 10 years of enzyme therapy in adults with Pompe disease

Neurology. 2019 Nov 5;93(19):e1756-e1767. doi: 10.1212/WNL.0000000000008441. Epub 2019 Oct 16.


Objective: To determine the effects of 10 years of enzyme replacement therapy (ERT) in adult patients with Pompe disease, focusing on individual variability in treatment response.

Methods: In this prospective, multicenter cohort study, we studied 30 patients from the Netherlands and France who had started ERT during the only randomized placebo-controlled clinical trial with ERT in late-onset Pompe disease (NCT00158600) or its extension (NCT00455195) in 2005 to 2008. Main outcomes were walking ability (6-minute walk test [6MWT]), muscle strength (manual muscle testing using Medical Research Council [MRC] grading), and pulmonary function (forced vital capacity [FVC] in the upright and supine positions), assessed at 3- to 6-month intervals before and after the start of ERT. Data were analyzed with linear mixed-effects models for repeated measurements.

Results: Median follow-up duration on ERT was 9.8 years (interquartile range [IQR] 8.3-10.2 years). At the group level, baseline 6MWT was 49% of predicted (IQR 41%-60%) and had deteriorated by 22.2 percentage points (pp) at the 10-year treatment point (p < 0.001). Baseline FVC upright was 54% of predicted (IQR 47%-68%) and decreased by 11 pp over 10 years (p < 0.001). Effects of ERT on MRC sum score and FVC supine were similar. At the individual level, 93% of patients had initial benefit of ERT. Depending on the outcome measured, 35% to 63% of patients had a secondary decline after ≈3 to 5 years. Still, at 10 years of ERT, 52% had equal or better 6MWT and/or FVC upright compared to baseline.

Conclusions: The majority of patients with Pompe disease benefit from long-term ERT, but many patients experience some secondary decline after ≈3 to 5 years. Individual variation, however, is considerable.

Classification of evidence: This study provides Class IV evidence that for the majority of adults with Pompe disease, long-term ERT positively affects, or slows deterioration in, muscle strength, walking ability, and/or pulmonary function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Enzyme Replacement Therapy*
  • Female
  • Follow-Up Studies
  • France
  • Glycogen Storage Disease Type II / complications
  • Glycogen Storage Disease Type II / drug therapy*
  • Glycogen Storage Disease Type II / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Mobility Limitation
  • Muscle Strength
  • Muscle Weakness / etiology
  • Muscle Weakness / physiopathology
  • Netherlands
  • Noninvasive Ventilation / statistics & numerical data
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Respiratory Insufficiency / etiology
  • Respiratory Insufficiency / physiopathology
  • Respiratory Insufficiency / therapy
  • Treatment Outcome
  • Vital Capacity
  • Walk Test
  • Wheelchairs
  • alpha-Glucosidases / therapeutic use*


  • GAA protein, human
  • alpha-Glucosidases