Reevaluating measures of disease progression in facioscapulohumeral muscular dystrophy

• Published in: Neuromuscular disorders : NMD Vol. 23; no. 4; pp. 306 - 312
• Main Authors: Statland, Jeffrey M., McDermott, Michael P., Heatwole, Chad, Martens, William B., Pandya, Shree, van der Kooi, E.L., Kissel, John T., Wagner, Kathryn R., Tawil, Rabi
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.04.2013
• Subjects: Adult; All clinical trials; All neuromuscular disease; Clinical trials methodology/study design; Disease Progression; Female; Humans; Isometric Contraction - physiology; Longitudinal Studies; Male; Middle Aged; Muscle disease; Muscle Strength - physiology; Muscle, Skeletal - physiopathology; Muscular Dystrophy, Facioscapulohumeral - physiopathology; Neurology; Outcome research; Randomized Controlled Trials as Topic; Outcome research; All clinical trials; Clinical trials methodology/study design; Muscle disease; All neuromuscular disease
• ISSN: 0960-8966; 1873-2364; 1873-2364
• DOI: 10.1016/j.nmd.2013.01.008

Recent advances in the understanding of the molecular pathophysiology of facioscapulohumeral muscular dystrophy (FSHD) have identified potential therapeutic targets. Consequently, an accurate understanding of disease progression in FSHD is crucial for the design of future clinical trials. Data from 228 subjects in 3 clinical trials and 1 natural history study were compared to examine disease progression in FSHD. All studies utilized the same techniques for manual muscle testing and maximum voluntary isometric contraction testing. Both techniques yield a total strength score that can be followed over time as an indicator of disease progression. Whereas natural history data showed a decrease in strength over 1year, there was an apparent increase in strength at 6months in 2 of the 3 clinical trials in both the placebo and treatment groups, that persisted for up to 1year for maximum voluntary isometric contraction testing. Variability estimates from the clinical trial data were consistent with those seen in the natural history data. Patients in clinical trials in FSHD may have better outcomes than those in natural history studies, regardless of treatment assignment, emphasizing the importance of placebo groups and the need for caution when interpreting the strength results of controlled and uncontrolled trials.