Categorising trajectories and individual item changes of the North Star Ambulatory Assessment in patients with Duchenne muscular dystrophy

Abstract

Functional variability among boys with Duchenne muscular dystrophy (DMD) is well recognised and complicates interpretation of clinical studies. We hypothesised that boys with DMD could be clustered into groups sharing similar trajectories of ambulatory function over time, as measured by the North Star Ambulatory Assessment (NSAA) total score. We also explored associations with other variables such as age, functional abilities, and genotype. Using the NorthStar Clinical Network database, 395 patients with >1 NSAA assessment were identified. We utilised latent class trajectory analysis of longitudinal NSAA scores, which produced evidence for at least four clusters of boys sharing similar trajectories versus age in decreasing order of clinical severity: 25% of the boys were in cluster 1 (NSAA falling to ≤ 5 at age ~10y), 35% were in cluster 2 (NSAA ≤ 5 ~12y), 21% in were cluster 3 (NSAA≤ 5 ~14y), and 19% in cluster 4 (NSAA > 5 up to 15y). Mean ages at diagnosis of DMD were similar across clusters (4.2, 3.9, 4.3, and 4.8y, respectively). However, at the first NSAA assessment, a significant (p<0.05) association was observed between earlier declining clusters and younger age, worse NSAA, slower rise from supine, slower 10 metre walk/run times, and younger age of steroid initiation. In order to assess the probability of observing complete loss of function for individual NSAA items, we examined the proportion of patients who shifted from a score of 1 or 2 at baseline to a score of 0. We also assessed the probability of gain of function using the inverse assessment and stratified the probability of deterioration, improvement–or static behavior–by age ranges and using baseline functional status. Using this tool, our study provides a comprehensive assessment of the NSAA in a large population of patients with DMD and, for the first time, describes discrete clusters of disease progression; this will be invaluable for future DMD clinical trial design and interpretation of findings.

Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy

“…It does, however, reflect an activity important for daily living. There is an emerging consensus that NSAA may be the best outcome measure for ambulatory patients with DMD [47][48][49][50] . However, the lack of efficacy in several secondary function and biomarker endpoints is consistent with the lack of efficacy in the 4SC measurement and suggests that the selection of 4SC as the primary endpoint was not the sole cause for the negative outcome in this trial.…”

Muscle metabolic remodelling patterns in Duchenne muscular dystrophy revealed by ultra-high-resolution mass spectrometry imaging

“…Currently, several functional tests are used such as the 6 min walk test, the North Star ambulatory assessment, and the performance of upper limb test or time items in addition to muscular imaging. However, these tests are often ineffective, and their results do not necessarily correlate with the patient’s condition 9 . Owing to wide phenotypic variability, reliable outcome measurements that would enable assessing treatment efficacy remain tentative, and new biomarkers must be identified to better understand the DMD pathophysiology and more accurately evaluate patient prognosis and follow-up 1 .…”

Characteristics of Disease Progression and Genetic Correlation in Ambulatory Iranian Boys With Duchenne Muscular Dystrophy

“…Although in the UK NorthStar database study and other researches LOA median age mentioned 13-yearold (Ricotti et al 2016, Muntoni et al 2019). The contracture was seen in 38.9 % and progressive weakness in 86.2%.…”