Kristina Gutschmidt1, Olimpia Musumeci2, Jordi Díaz-Manera3,4,5, Yin-Hsiu Chien6, Karl Christian Knop7, Stephan Wenninger1, Federica Montagnese1, Alessia Pugliese2, Graziana Tavilla2, Jorge Alonso-Pérez3, Paul Wuh-Liang Hwu6, Antonio Toscano2, Benedikt Schoser8. 1. Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians University Munich, Ziemssenstr. 1, 80336, Munich, Germany. 2. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. 3. Neurology Department, Neuromuscular Diseases Unit, Hospital de La Santa Creu I Sant Pau and Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain. 4. Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Valencia, Spain. 5. John Walton Muscular Dystrophy Research Center, University of Newcastle, Newcastle, UK. 6. Department of Medical Genetics and Pediatrics, National Taiwan University Hospital, Taipei, Taiwan. 7. Neurologische Praxis Neuer Wall, Hamburg, Germany. 8. Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians University Munich, Ziemssenstr. 1, 80336, Munich, Germany. benedikt.schoser@med.uni-muenchen.de.
Abstract
BACKGROUND: Pompe disease is one of the few neuromuscular diseases with an approved drug therapy, which has been available since 2006. Our study aimed to determine the real-world long-term efficacy and safety of alglucosidase alfa. METHODS: This multicenter retrospective study (NCT02824068) collected data from adult Pompe disease patients receiving ERT for at least 3 years. Demographics and baseline characteristics, muscle strength, lung function (FVC), walking capability (6MWT), and safety were assessed once a year. Evaluation was done on the group and individual levels, using quantitative linear models (t test) and general univariate linear models (ANOVA). FINDINGS: Sixty-eight adult Pompe disease patients from four countries (Spain, Taiwan, Italy, Germany (STIG)) participated. The mean follow-up was 7.03 years ± 2.98. At group level in all outcome measures, an initial improvement followed by a secondary decline was observed. After 10 years, the 6MWT%pred showed the most sustained positive effect (p = 0.304). The MRC%max remained stable with a mild decline (p = 0.131), however, FVC%pred deteriorated significantly (p < 0.001) by 14.93% over 10 years of ERT. The progression rate of FVC%pred under ERT could be explained in most of the patients (83.5%) by the disease severity at baseline. Furthermore, our study shows a decline in the FVC combined with an increase in non-invasive and invasive ventilation requirements in adult Pompe disease patients over time. CONCLUSIONS: The STIG real-world study confirms an initial efficacy of ERT in the first years with a secondary sustained decline in multiple outcome measures. Further efforts are required to establish a more valid long-term monitoring and improved therapies.
BACKGROUND: Pompe disease is one of the few neuromuscular diseases with an approved drug therapy, which has been available since 2006. Our study aimed to determine the real-world long-term efficacy and safety of alglucosidase alfa. METHODS: This multicenter retrospective study (NCT02824068) collected data from adult Pompe disease patients receiving ERT for at least 3 years. Demographics and baseline characteristics, muscle strength, lung function (FVC), walking capability (6MWT), and safety were assessed once a year. Evaluation was done on the group and individual levels, using quantitative linear models (t test) and general univariate linear models (ANOVA). FINDINGS: Sixty-eight adult Pompe disease patients from four countries (Spain, Taiwan, Italy, Germany (STIG)) participated. The mean follow-up was 7.03 years ± 2.98. At group level in all outcome measures, an initial improvement followed by a secondary decline was observed. After 10 years, the 6MWT%pred showed the most sustained positive effect (p = 0.304). The MRC%max remained stable with a mild decline (p = 0.131), however, FVC%pred deteriorated significantly (p < 0.001) by 14.93% over 10 years of ERT. The progression rate of FVC%pred under ERT could be explained in most of the patients (83.5%) by the disease severity at baseline. Furthermore, our study shows a decline in the FVC combined with an increase in non-invasive and invasive ventilation requirements in adult Pompe disease patients over time. CONCLUSIONS: The STIG real-world study confirms an initial efficacy of ERT in the first years with a secondary sustained decline in multiple outcome measures. Further efforts are required to establish a more valid long-term monitoring and improved therapies.
Entities:
Keywords:
Alglucosidase alpha; Efficacy; Enzyme replacement therapy; Glycogen storage disease type 2; Long term follow-up; Pompe disease
Authors: N A M E van der Beek; M L C Hagemans; A T van der Ploeg; A J J Reuser; P A van Doorn Journal: Acta Neurol Belg Date: 2006-06 Impact factor: 2.396
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