Journal Article

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

Reuser, Arnold JJ, Karstens, Francois PJ, de Visser, Marianne, Verschuuren, Jan JGM, Faber, Catharina G, van der Kooi, Anneke J, Kruijshaar, Michelle E, Hop, Wim CJ, Notermans, Nicolette C, Wokke, John H, de Vries, Juna M, Kuks, Jan BM, van der Ploeg, Ans T, van Doorn, Pieter A, van Engelen, Baziel GM, van der Beek, Nadine AME

2012

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acid α-glucosidase / Adult / Adults / Aged / Alglucosidase alfa / alpha-Glucosidases - therapeutic use / Amylases / Biopharmaceutics / Cohort Studies / Disease / Enzyme replacement therapy / Enzymes / Female / Glycogen / Glycogen storage disease type II / Glycogen Storage Disease Type II - drug therapy / Glycogen Storage Disease Type II - enzymology / Glycogen Storage Disease Type II - physiopathology / Health aspects / Hospitals / Human Genetics / Humans / Labels / Lung function / Lysosomal storage disorder / Male / Medical research / Medicine / Medicine & Public Health / Metabolic disorders / Middle Aged / Muscle strength / Muscle, Skeletal - physiopathology / OMIM number 232300 / Pharmacology/Toxicology / Pompe disease / Prognosis / Rare diseases / Ratings & rankings / Respiration, Artificial / Respiratory Function Tests