TY - JOUR
T1 - Predicting trajectories of the north star ambulatory assessment total score in Duchenne muscular dystrophy
AU - PRO-DMD-01 study investigators, Association Française contre les Myopathies¶, The NorthStar Clinical Network
AU - Muntoni, Francesco
AU - Signorovitch, James
AU - Goemans, Nathalie
AU - Manzur, Adnan Y.
AU - Done, Nicolae
AU - Sajeev, Gautam
AU - Li, Jiayang
AU - Akbarnejad, Hanane
AU - Sharma, Aarushi
AU - Ward, Susan J.
AU - Niks, Erik H.
AU - Servais, Laurant
AU - Mercuri, Eugenio
AU - Guglieri, Michela
AU - Straub, Volker
AU - de Groot, Imelda
AU - Ridout, Deborah
AU - Deconinck, Nicolas
AU - Tulinius, Mar
AU - Flanigan, Kevin
AU - Henricson, Erik
AU - de Resende, Maria Bernadete Dutra
AU - Vita, Gian Luca
AU - Schara, Ulrike
AU - Kirschner, Jan Berd
AU - Topaloglu, Haluk
AU - Monges, Soledad
AU - Cances, Claude
AU - Domingos, Joana
AU - Ricotti, Valeria
AU - Selby, Victoria
AU - Wolfe, Amy
AU - Abbott, Lianne
AU - Milev, Evelin
AU - Panagiotopoulou, Efthymia
AU - Iodice, Mario
AU - Ash, Maria
AU - Servais, Laurent
AU - Voit, Thomas
AU - Decostre, Valérie
AU - Gilabert, Stéphanie
AU - Hogrel, Jean Yves
AU - Murphy, Alexander
AU - Mayhew, Anna
AU - Van der Holst, Menno
AU - Krom, Yvonne D.
AU - van Heur-Neuman, Marjolein J.
AU - de Groot, Imelda J.M.
AU - Jansen, Merel
AU - Pelsma, Maaike
N1 - Publisher Copyright:
Copyright © 2025 Muntoni et al.
PY - 2025/6
Y1 - 2025/6
N2 - 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 ±3.6, 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.
AB - 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 ±3.6, 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.
UR - https://www.scopus.com/pages/publications/105009466219
U2 - 10.1371/journal.pone.0325736
DO - 10.1371/journal.pone.0325736
M3 - Article
C2 - 40577272
AN - SCOPUS:105009466219
SN - 1932-6203
VL - 20
JO - PLoS ONE
JF - PLoS ONE
IS - 6 June
M1 - e0325736
ER -