Abstract Details

Title Predicting Trajectories of Ambulatory Function in Duchenne Muscular Dystrophy (DMD)

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P13 - Poster Session 13 (8:00 AM-9:00 AM)

Poster/Presentation
Number 11-006

Objective To develop prognostic models for trajectories of ambulatory function in DMD for up to 4 years of follow-up.

Background The North Star Ambulatory Assessment (NSAA) is a validated assessment that serves as an endpoint in multiple DMD clinical trials. Accurately predicting NSAA trajectories is important for understanding effects of novel therapies, via creation of individualized controls for treated patients, especially over longer-term (>18 month) follow-up for which placebo controls are infeasible.

Design/Methods Longitudinal NSAA data for boys with DMD aged 4-10 years and starting with NSAA >12 at baseline were drawn from four natural history databases: UZ Leuven, PRO-DMD-01 (provided by CureDuchenne), the North Star Clinical Network and iMDEX. NSAA total score trajectories were fit using mixed effects models with age, steroid use, height, weight and ambulatory function as baseline predictors. Predictive accuracy was evaluated in a held-out sample.

Results Among N=261 subjects, mean age at baseline was 6.8 years, mean NSAA score was 25.6; 53% were receiving prednisone, 23% deflazacort, and 24% no steroid. Almost all initiated steroids within the first year of follow-up. The average patient had 6 post-baseline NSAA assessments over 2-4 years of follow-up. Important predictors of greater decline in NSAA identified in the training sample (N=208) included older age, longer rise-from-floor times, higher NSAA (more room to decline), greater height, and greater body mass index. The best-fitting model explained 27% of variation in post-baseline NSAA with average prediction errors of ±5.6 units (root mean squared error) in a held-out sample (N=53). An increasing likelihood of missing NSAA data was evident as boys approached worse function.

Conclusions Trajectories of ambulatory function in DMD can be well-predicted using baseline characteristics. However missing NSAA assessments may bias predictions, most likely towards better-than-actual outcomes. Additional validation in larger samples and assessments of missing data are warranted.

Authors/Disclosures
Francesco Muntoni, MD (UCL Institute of Child Health) PRESENTER	Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sarepta. Dr. Muntoni has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Biogen. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. The institution of Dr. Muntoni has received research support from European Commission. The institution of Dr. Muntoni has received research support from Medical Research Council. The institution of Dr. Muntoni has received research support from Biogen. The institution of Dr. Muntoni has received research support from Muscular Dystrophy UK. The institution of Dr. Muntoni has received research support from MDA USA. The institution of Dr. Muntoni has received research support from Sarepta. The institution of Dr. Muntoni has received research support from Association Francoise Myopathies. Dr. Muntoni has received personal compensation in the range of $0-$499 for serving as a Clinical expert with UK NICE Committee.
	No disclosure on file
Nathalie M. Goemans, MD (University Hospitals Leuven)	Dr. Goemans has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Goemans has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Goemans has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Goemans has received publishing royalties from a publication relating to health care.
	No disclosure on file
Nicolae Done, PhD (Analysis Group)	Dr. Done has received personal compensation for serving as an employee of Analysis Group, Inc.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Craig McDonald, MD (UC Davis Dept. of PM&R)	Dr. McDonald has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for PTC Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Solid Biosciences. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Solid Biosciences. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Edgewise Therapeutics. The institution of Dr. McDonald has received research support from Sarepta Therapeutics. The institution of Dr. McDonald has received research support from PTC Therapeutics. The institution of Dr. McDonald has received research support from Edgewise Therapeutics. The institution of Dr. McDonald has received research support from Capricor Therapeutics. The institution of Dr. McDonald has received research support from Italfarmaco. Dr. McDonald has received research support from NS Pharma. The institution of Dr. McDonald has received research support from NIH (NINDS). The institution of Dr. McDonald has received research support from Parent Project Muscular Dystrophy. The institution of Dr. McDonald has received research support from Muscular Dystrophy Association. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Member National Advisory Board for Medical Rehabilitation Research with NIH.

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