The disease also affects the respiratory muscles resulting in the need for ventilatory support in a high proportion of patients Patients with late-onset Pompe disease usually present with progressive muscle weakness (often in a limb-girdle pattern) and loss of muscular function, leading to problems with activities of daily living (ADL), reduced mobility, and eventually wheelchair use. Late-onset Pompe disease may develop in children and adults of any age, and presents with a wide spectrum of clinical phenotypes
Overall incidence ranges from 1 in 33,000 persons to 1 in 300,000 persons, depending on geographic region and ethnicity Late-onset Pompe disease (also known as glycogen storage disease type II or acid α-glucosidase deficiency) is a rare lysosomal storage disorder caused by a genetic deficiency in the enzyme acid α-glucosidase.
This is of particular relevance in studies that investigate treatment efficacy in chronic, progressive diseases such as the lysosomal storage disorders.
#SNIP FLORENCE SC TRIAL#
Establishing the MCID for study endpoints allows the clinical relevance of efficacy data from published trial results to be determined. One of the key factors in the evaluation of an intervention in controlled clinical trials is the clinical relevance of the selected study endpoints or outcome measures, together with an understanding of what comprises a minimal clinically important difference (MCID) in these endpoints. Given that the relevance to patients with late-onset Pompe disease of the 6MWT or FVC MCIDs established for chronic respiratory diseases is unclear, these measures should be evaluated specifically in late-onset Pompe disease and alternative outcome measures more specific to neuromuscular disease considered. Outcome measures in muscular dystrophies include composite measures of muscle function and gait, as well as Rasch-designed and validated tools to assess disease-related quality of life and activities of daily living. However, applying the 6MWT and FVC MCIDs from studies of chronic respiratory diseases to late-onset Pompe disease has several important limitations. In 6 of the 9 late-onset Pompe disease studies that reported FVC, the changes from baseline in percentage predicted FVC were above or within the MCID established in respiratory diseases and the difference was perceived as either an improvement or stabilization by patients. Clinical improvement was perceived by patients in 6 of the 10 studies. In 9 of the 10 late-onset Pompe disease studies reviewed, changes from baseline in the 6MWT were above or within the MCID established in respiratory diseases. The MCIDs determined in studies of chronic respiratory diseases were used to analyze the results of clinical studies of enzyme replacement therapy in late-onset Pompe disease. A literature search was carried out to identify studies reporting the MCID (absolute and relative) for the 6MWT and FVC in other diseases. However, the relevance of these markers to late-onset Pompe disease and the minimal clinically important difference (MCID) for these endpoints in late-onset Pompe disease have not yet been established. Studies of patients with late-onset Pompe disease have used endpoints such as the 6-minute walking test (6MWT) and forced vital capacity (FVC) to assess muscular and respiratory function during disease progression or treatment. Pompe disease/glycogen storage disease type II, is a rare, lysosomal storage disorder associated with progressive proximal myopathy, causing a gradual loss of muscular function and respiratory insufficiency.
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