Pulmonary function in patients with Duchenne muscular dystrophy from the STRIDE Registry and CINRG Natural History Study: a matched cohort analysis



Poster Number: T327


Christian Werner, MD, PTC Therapeutics, Már Tulinius, Dept of Pediatrics, Gothenburg University, Queen Silvia Children’s Hospital, Gothenburg, Sweden, Filippo Buccella, Parent Project APS Italy, Rome, Italy, Isabelle Desguerre, Hôpital Necker – Enfants Malades, Paris, France, Janbernd Kirschner, PhD, Medical Center – University of Freiburg, Freiberg, Germany, Eugenio Maria Mercuri, MD, PhD, POLICLINICO UNIV A. GEMELLI - DIV NEUROPSICHIATRIA INFANTILE, Francesco Muntoni, University College London, Great Ormond Street Institute of Child Health, London, United Kingdom, Andrés Nascimento Osorio, MD, Hospital Sant Joan de Déu, Unidad de Patología Neuromuscular, Universidad de Barcelona, Spain, Maria Bernadete Dutra de Resende, Department of Neurology, Faculty of Medicine, University of São Paulo, São Paulo SP, Brazil, Lauren Morgenroth, MS, CGC, TRiNDS, LLC, Heather Gordish-Dressman, PhD, Children's National Medical Center, Shelley Johnson, PTC Therapeutics Inc., South Plainfield, NJ, USA, Anbu Balaji, PTC Therapeutics Inc., South Plainfield, NJ, USA, Emelline Liu, PTC Therapeutics Inc., South Plainfield, NJ, USA, Rajani Rajbhandari, PTC Therapeutics Inc., South Plainfield, NJ, USA, Bethany Freel, PhD, PTC Therapeutics, South Plainfield, NJ, USA, Jonathan Blaize, PhD, PTC Therapeutics, South Plainfield, NJ, USA, Craig M. McDonald, MD, University of California Davis School of Medicine, Davis, CA, USA

Background: Strategic Targeting of Registries and International Database of Excellence (STRIDE; NCT02369731) is an ongoing, multicenter, observational registry providing data on ataluren use in nonsense mutation Duchenne muscular dystrophy (nmDMD) patients in routine clinical practice.

Objective: We investigated whether nmDMD patients receiving ataluren plus standard of care (SoC) in the STRIDE Registry experienced a lesser decline in pulmonary function versus DMD patients receiving SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Natural History Study (NCT00468832).

Methods: Data were extracted on January 31, 2023. Propensity score matching identified STRIDE and CINRG patient cohorts (N=277) comparable in established predictors of disease progression: age at first symptoms; age at initiation of corticosteroid use; duration of deflazacort use; and duration of other corticosteroid use. Patients from CINRG who had received investigational drugs for DMD were excluded from this analysis. Kaplan–Meier analyses were used to estimate ages at %-predicted forced vital capacity (FVC) <60% and 50%. Results: The mean (SD) ages at onset of first symptoms (STRIDE vs CINRG; N=277 per cohort) were 2.8 (1.7) and 2.9 (1.5) years, respectively. Most patients (STRIDE vs CINRG) received corticosteroids for ≥12 months (88.8% vs 89.2%), with a similar proportion receiving deflazacort (52.0% vs 47.7%) or other corticosteroids (44.8% vs 48.4%). Median (95% confidence interval [CI]) ages at %-predicted FVC <60% (STRIDE vs CINRG) were 17.7 (16.9, 19.9) and 15.6 (15.1, 16.4) years, respectively (HR [95% CI] 0.630 [0.440, 0.903]; p=0.0086). Median (95% CI) ages at %-predicted FVC <50% (STRIDE vs CINRG) were 19.2 (17.8, not estimable) and 17.7 (16.5, 18.6) years, respectively (HR [95% CI] 0.630 [0.426, 0.932]; p=0.0206). Conclusions: These real-world, multi-country data suggest that treatment with ataluren and SoC in routine clinical practice slows disease progression in pulmonary function in nmDMD patients.