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

Abstract

BackgroundEnzyme 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.MethodsPatients 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.ResultsSixty-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.ConclusionsWe 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.

Observational clinical study of 22 adult-onset Pompe disease patients undergoing enzyme replacement therapy over 5years

“…Patients are more likely to improve if they are younger, independent of artificial ventilation, have a better FVC in upright position, and have less severe muscle weakness at the start of treatment. This suggests that starting ERT early in the disease course may be beneficial [35]. Our study did not confirm these findings however, the low number (n = 7) of younger patients (below the age of 40), mean that this result should be interpreted with caution.…”

“…The age-related differences in supine FVC % were noticed previously [35] with a significant decline in supine FVC % in the elderly. Patients are more likely to improve if they are younger, independent of artificial ventilation, have a better FVC in upright position, and have less severe muscle weakness at the start of treatment.…”

Urge Incontinence and Gastrointestinal Symptoms in Adult Patients with Pompe Disease: A Cross-Sectional Survey

“…Enzyme replacement therapy (ERT) with alglucosidase alfa (Myozyme ® ) for patients with classic infantile and late-onset Pompe disease has been available since 2006 (Toscano and Schoser 2013). The main clinical and prognostic features in adult patients with Pompe disease are proximal and axial paresis in the limb girdles and respiratory insufficiency due to glycogen storage in the skeletal muscles (van der Beek et al 2012). ERT was shown to have a beneficial effect on these symptoms and to delay progression of skeletal muscle symptoms in adolescent and adult patients with Pompe disease (Regnery et al 2012;Laforêt et al 2013;G€ ung€ or et al 2013;Schneider et al 2013;de Vries et al 2012;Toscano and Schoser 2013).…”

Profile of alglucosidase alfa in the treatment of Pompe disease: safety, efficacy, and patient acceptability

“…57,58 Secondly, effectiveness of ERT is dependent on the rhGAA uptake in the skeletal muscles that is limited by a low expression of the cation-independent mannose-6-phosphate receptor (CI-MPR). 59,60 Women seem to benefit more from ERT than males 61 in respect to muscle strength because of a higher dose uptake of alglucosidase per gram of muscle fiber due to their smaller fibers with a higher surface-to-volume ratio.…”