Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study

Background: Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors. Methods: Patients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3-6 months and analyzed using repeated-measures ANOVA. Results: Sixty-nine patients (median age 52.1 years) were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y); hand-held dynamometry 4.0 pp/y; both p < 0.001). Forced vital capacity (FVC) remained stable when measured in upright, but declined in supine position (-1.1 pp/y; p = 0.03). Muscle function did not improve in all patients (quick motor function test 0.7 pp/y; p = 0.14), but increased significantly in wheelchair-independent patients and those with mild and moderate muscle weakness. Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up), ERT affected muscle strength positively (manual muscle testing +3.3 pp/y, p < 0.001 and hand-held dynamometry +7.9 pp/y, p < 0.001). Its effect on upright FVC was +1.8 pp/y (p = 0.08) and on supine FVC +0.8 (p = 0.38). Favorable prognostic factors were female gender for muscle strength, and younger age and better clinical status for supine FVC. Conclusions: We conclude that ERT positively alters the natural course of Pompe disease in adult patients; muscle strength increased and upright FVC stabilized. Functional outcome is probably best when ERT intervention is timely.