Abstract
BackgroundLate-onset Pompe disease (LOPD) is a rare, metabolic disease primarily affecting the musculoskeletal and respiratory systems. Forced vital capacity (FVC) is commonly used to measure pulmonary function; however, associations between FVC and other LOPD outcomes remain unclear.MethodsA systematic literature review was conducted on November 2015, updated September 2016 and supplemented with clinical trial data from the sponsor. Outcomes included: 6-min walk test distance (6MWT), FVC, maximal inspiratory/expiratory pressure (MIP/MEP), Medical Research Council-skeletal muscle strength score (MRC), 36-item short-form survey-physical component score (SF-36), Rotterdam Handicap Scale (RHS), Fatigue Severity Scale (FSS) and survival. Individual patient data meta-analysis was used for cross-sectional analyses and longitudinal analyses to determine associations between percent of predicted FVC and LOPD measures and outcomes.ResultsFifteen studies were selected. From cross-sectional analyses, FVC and MRC were most strongly associated. Specifically, patients with 10% higher FVC (a round number for illustrative purposes only) were associated with a 4.72% (95% confidence interval [CI]: 3.37, 6.07) higher MRC score, indicating a positive association. Similarly, slopes for the 6MWT and SF-36 relative to a 10% higher FVC were estimated at 33.2 meters (95% CI 24.0, 42.4) and 1.2% (95% CI 0.24, 2.16%), respectively. From longitudinal analyses, a 10% incremental increase in predicted FVC was associated with an average increase of 4.12% in MRC score (95% CI 1.29, 6.95), 35.6 m in the 6MWT (95% CI 19.9, 51.6), and 1.34% in SF-36 (95% CI 0.08, 2.60). There was insufficient data to conduct analyses for RHS, FSS and survival.ConclusionsFVC is positively associated with LOPD measures and outcomes across multiple domains. Additionally, longitudinal changes in FVC are positively associated with changes in the 6MWT, MRC and SF-36.
Highlights
Late-onset Pompe disease (LOPD) is a rare metabolic disease caused by a deficiency of acid α-glucosidase (GAA) resulting in the accumulation of glycogen in primarily skeletal and cardiac muscles [1]
Forced vital capacity (FVC) is a measure of respiratory function that is among the more commonly reported outcomes assessed in LOPD patients as respiratory function is a key area of impact for the disease, and FVC is an objective and reproducible parameter that is readily measurable across most settings
FVC was a primary endpoint of the Late Onset Treatment Study and Extension (LOTS) [3, 4], as well as other studies that demonstrate the efficacy of enzyme replacement therapy (ERT) with alglucosidase alfa
Summary
Late-onset Pompe disease (LOPD) is a rare metabolic disease caused by a deficiency of acid α-glucosidase (GAA) resulting in the accumulation of glycogen in primarily skeletal and cardiac muscles [1]. As LOPD tends to affect the whole body, there are several outcome measures that are used to assess disease progression within an LOPD patient. Forced vital capacity (FVC) is a measure of respiratory function that is among the more commonly reported outcomes assessed in LOPD patients as respiratory function is a key area of impact for the disease, and FVC is an objective and reproducible parameter that is readily measurable across most settings. Individual patient data meta-analysis was used for cross-sectional analyses and longitudinal analyses to determine associations between percent of predicted FVC and LOPD measures and outcomes. Longitudinal changes in FVC are positively associated with changes in the 6MWT, MRC and SF-36
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