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Lookup NU author(s): Professor Michela GuglieriORCiD, Professor Volker StraubORCiD, Dr Anna Mayhew, Emerita Professor Katherine Bushby, Robert Muni Lofra, Meredith JamesORCiD, Dionne Moat, Jassi Sodhi
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Copyright © 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 ±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.
Author(s): Muntoni F, Signorovitch J, Goemans N, Done N, Sajeev G, Li J, Akbarnejad H, Sharma A, Ward SJ, Niks EH, Servais L, Mercuri E, Guglieri M, Straub V, de Groot I, Ridout D, Deconinck N, Tulinius M, Flanigan K, Henricson E, de Resende MBD, Vita GL, Schara U, Kirschner J, Topaloglu H, Monges S, Cances C, Domingos J, Ricotti V, Selby V, Wolfe A, Abbott L, Milev E, Panagiotopoulou E, Iodice M, Ash M, Servais L, Voit T, Decostre V, Gilabert S, Hogrel J-Y, Murphy A, Mayhew A, Van der Holst M, Krom YD, van Heur-Neuman MJ, de Groot IJ, Jansen M, Pelsma M, Bobbert M, Verschuuren JJGM, Manzur A, Manzur A, Robb S, Quinlivan R, Sarkozy A, Munot P, Baranello G, Scoto M, Main M, Patel H, Samsuddin S, Gupta VA, Bushby K, Bertolli C, Muni-Lofra R, James M, Moat D, Sodhi J, Roper H, Parasuraman D, McMurchie H, Rabb R, Pysden K, Pallant L, Peachey G, Madhu R, Shillington A, Jungbluth H, Sheehan J, Spahr R, Bateman E, Cammiss C, Groves L, Emery N, Baxter P, Goulborne N, Senior M, Scott E, Hartley L, Parsons B, Mason F, Jenkins L, Toms B, Frimpong-Ansah C, Jarvis H, Dalgleish J, Keddie A, Di Marco M, Dunne J, Miah A, Selley A, Geary M, Palmer J, Greenfield K, MacAuley S, Robbins H, Iqbal M, Ward C, Taylor J, O'Hara A, Tewnion J, Chandratre S, Ramdas S, White M, Ramjattan H, Yirrel J, Van den Hauwe M, McDonald C
Publication type: Article
Publication status: Published
Journal: PLoS ONE
Year: 2025
Volume: 20
Issue: 6
Print publication date: 01/06/2025
Online publication date: 27/06/2025
Acceptance date: 16/05/2025
Date deposited: 14/07/2025
ISSN (electronic): 1932-6203
Publisher: Public Library of Science
URL: https://doi.org/10.1371/journal.pone.0325736
DOI: 10.1371/journal.pone.0325736
Data Access Statement: All relevant aggregate data are reported within the paper and the Supporting Information files. This study uses third party data sources accessed by the cTAP, through data use agreements with the relevant data holders. Individual-level data for some of these data sources are available on public repositories, and can be accessed through requests to the data holders via these repositories. PRO-DMD-01 study: Subject-level data from the PRO-DMD-01 study were provided by CureDuchenne. Data for this study (https://doi.org/10.25934/00005087) can be requested through Vivli (https://www.vivli.org). Other data sources used are not available on public repositories and may be available via data use agreements with the individual data holders. Requests for individual patient data may be directed towards the individual institutions/organizations that have collected and curated these patient data. [further contacts details given].
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