Predicting trajectories of the north star ambulatory assessment total score in Duchenne muscular dystrophy.
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 con...
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Public Library of Science (PLoS)
2025-01-01
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| Online Access: | https://doi.org/10.1371/journal.pone.0325736 |
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| author | Francesco Muntoni James Signorovitch Nathalie Goemans Adnan Y Manzur Nicolae Done Gautam Sajeev Jiayang Li Hanane Akbarnejad Aarushi Sharma Susan J Ward Erik H Niks Laurant Servais Eugenio Mercuri Michela Guglieri Volker Straub Imelda de Groot Deborah Ridout PRO-DMD-01 study investigators Association Française contre les Myopathies NorthStar Clinical Network Craig McDonald |
| author_facet | Francesco Muntoni James Signorovitch Nathalie Goemans Adnan Y Manzur Nicolae Done Gautam Sajeev Jiayang Li Hanane Akbarnejad Aarushi Sharma Susan J Ward Erik H Niks Laurant Servais Eugenio Mercuri Michela Guglieri Volker Straub Imelda de Groot Deborah Ridout PRO-DMD-01 study investigators Association Française contre les Myopathies NorthStar Clinical Network Craig McDonald |
| author_sort | Francesco Muntoni |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e6405c7f52ef468ebc1dae2101156e1b |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-e6405c7f52ef468ebc1dae2101156e1b2025-08-20T03:28:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01206e032573610.1371/journal.pone.0325736Predicting trajectories of the north star ambulatory assessment total score in Duchenne muscular dystrophy.Francesco MuntoniJames SignorovitchNathalie GoemansAdnan Y ManzurNicolae DoneGautam SajeevJiayang LiHanane AkbarnejadAarushi SharmaSusan J WardErik H NiksLaurant ServaisEugenio MercuriMichela GuglieriVolker StraubImelda de GrootDeborah RidoutPRO-DMD-01 study investigatorsAssociation Française contre les MyopathiesNorthStar Clinical NetworkCraig McDonaldThe 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.https://doi.org/10.1371/journal.pone.0325736 |
| spellingShingle | Francesco Muntoni James Signorovitch Nathalie Goemans Adnan Y Manzur Nicolae Done Gautam Sajeev Jiayang Li Hanane Akbarnejad Aarushi Sharma Susan J Ward Erik H Niks Laurant Servais Eugenio Mercuri Michela Guglieri Volker Straub Imelda de Groot Deborah Ridout PRO-DMD-01 study investigators Association Française contre les Myopathies NorthStar Clinical Network Craig McDonald Predicting trajectories of the north star ambulatory assessment total score in Duchenne muscular dystrophy. PLoS ONE |
| title | Predicting trajectories of the north star ambulatory assessment total score in Duchenne muscular dystrophy. |
| title_full | Predicting trajectories of the north star ambulatory assessment total score in Duchenne muscular dystrophy. |
| title_fullStr | Predicting trajectories of the north star ambulatory assessment total score in Duchenne muscular dystrophy. |
| title_full_unstemmed | Predicting trajectories of the north star ambulatory assessment total score in Duchenne muscular dystrophy. |
| title_short | Predicting trajectories of the north star ambulatory assessment total score in Duchenne muscular dystrophy. |
| title_sort | predicting trajectories of the north star ambulatory assessment total score in duchenne muscular dystrophy |
| url | https://doi.org/10.1371/journal.pone.0325736 |
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