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.
Highlights
Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy
The aims of the current study were 1) to determine whether ERT alters the progressive course of Pompe disease in a broader adult patient population ranging from very severely affected to mildly affected; 2) to determine how much ERT alters the course of the disease relative to that reflected in pre-treatment data; and 3) to identify prognostic factors for response to treatment
ERT = Enzyme Replacement Therapy; pp/y = percentage points per year; 95% CI = 95% Confidence Interval; MRC sumscore = Medical Research Council sumscore; QMFT score = Quick Motor Function Test score; hand-held dynamometry (HHD) sumscore = Hand-Held Dynamometry sumscore; Forced vital capacity (FVC) = Forced Vital Capacity; N = Number of patients; M = Number of Measurements
Summary
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 identified potential prognostic factors. Pompe disease (OMIM number 232300) is an autosomal recessive metabolic myopathy caused by deficiency of the lysosomal enzyme acid α-glucosidase. This deficiency impairs lysosomal glycogen breakdown, leading to glycogen accumulation in several tissues [1,2,3,4]. The disease generally presents as a limb-girdle myopathy. Most patients lose ambulation and require ventilatory support [5,10,11,14,15]
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