Predicting trajectories of the north star ambulatory assessment total score in Duchenne muscular dystrophy

Copyright \ua9 2025 Muntoni et al. The North Star Ambulatory Assessment (NSAA) is a widely used functional endpoint in drug development for ambulatory patients with Duchenne muscular dystrophy (DMD). Accurately predicting NSAA total score trajectories is important for designing randomized trials for novel therapies in DMD and for contextualizing outcomes, especially over longer-term follow-up (>18 months) when placebo-controlled studies are infeasible. We developed a prognostic model for NSAA total score trajectories over at most 5 years of follow-up for patients with DMD aged 4 to < 16 years who were initially ambulatory and receiving corticosteroids but no other disease-modifying therapies. The model was based on longitudinal data from four natural history databases: UZ Leuven, PRO-DMD-01 (provided by CureDuchenne), the North Star Clinical Network, and iMDEX. Candidate predictors included age, height, weight, body mass index, steroid type and regime, NSAA total score, rise from floor velocity and 10-meter walk/run velocity, as well as DMD genotype class, index year, and data source. Among N=416 patients at baseline, mean age was 8.2 years, mean NSAA total score was 24, and 61% were receiving prednisone and 39% deflazacort, with the majority having been treated with daily corticosteroid regimens (69%) relative to other regimens (31%). Patients had an average of four NSAA assessments post-baseline during a median follow-up of 2.6 years (inter-quartile range 1.9 to 3.6 years). The best-fitting model in the full study sample explained 39% of the variation in NSAA total score changes, with prediction errors of \ub13.6, 5.1, 5.9, 7.5, 9.5 NSAA units during follow-up years 1-5, respectively. The most important predictors were baseline age, NSAA, rise from floor velocity, and 10-meter walk/run velocity. In conclusion, trajectories of ambulatory motor function in DMD, as measured by the NSAA total score, can be well-predicted using readily available baseline characteristics. We discuss applications of these predictions to DMD drug development

Meaningful changes in motor function in Duchenne muscular dystrophy (DMD): A multi-center study

\ua9 2024 Muntoni et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Evaluations of treatment efficacy in Duchenne muscular dystrophy (DMD), a rare genetic disease that results in progressive muscle wasting, require an understanding of the ‘meaningfulness’ of changes in functional measures. We estimated the minimal detectable change (MDC) for selected motor function measures in ambulatory DMD, i.e., the minimal degree of measured change needed to be confident that true underlying change has occurred rather than transient variation or measurement error. MDC estimates were compared across multiple data sources, representing >1000 DMD patients in clinical trials and real-world clinical practice settings. Included patients were ambulatory, aged ≥4 to <18 years and receiving steroids. Minimal clinically important differences (MCIDs) for worsening were also estimated. Estimated MDC thresholds for >80% confidence in true change were 2.8 units for the North Star Ambulatory Assessment (NSAA) total score, 1.3 seconds for the 4-stair climb (4SC) completion time, 0.36 stairs/second for 4SC velocity and 36.3 meters for the 6-minute walk distance (6MWD). MDC estimates were similar across clinical trial and real-world data sources, and tended to be slightly larger than MCIDs for these measures. The identified thresholds can be used to inform endpoint definitions, or as benchmarks for monitoring individual changes in motor function in ambulatory DMD