Age at loss of ambulation in patients with DMD from the STRIDE Registry and the CINRG Natural History Study: a matched cohort analysis

Topic:

Other

Poster Number: T328

Author(s):

Christian Werner, MD, PTC Therapeutics, Eugenio Maria Mercuri, MD, PhD, POLICLINICO UNIV A. GEMELLI - DIV NEUROPSICHIATRIA INFANTILE, Francesco Muntoni, FRCPCH, FMedSci, University College London, National Institute for Health Research Great Ormond Street Hospital, 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, Andrés Nascimento Osorio, MD, Hospital Sant Joan de Déu, Unidad de Patología Neuromuscular, Universidad de Barcelona, Spain, Már Tulinius, Dept of Pediatrics, Gothenburg University, Queen Silvia Children’s Hospital, Gothenburg, Sweden, 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) Registry (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 examined whether nmDMD patients receiving ataluren plus standard of care (SoC) in the STRIDE Registry experienced a delay in age at loss of ambulation (LOA) versus DMD patients receiving SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne 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. Kaplan–Meier analyses were used to estimate age at LOA.

Results: The mean (standard deviation) ages at first symptoms in the STRIDE and CINRG cohorts (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%). In the STRIDE cohort, 33.9% (94/277) of patients lost ambulation compared with 53.1% (147/277) of patients in the CINRG cohort. The median (95% confidence interval) ages at LOA (STRIDE vs CINRG) were 16.5 (14.4,19.7) and 13.0 (12.3, 13.8) years, respectively. Kaplan–Meier analyses showed that ataluren plus SoC delayed age at LOA compared with SoC alone (hazard ratio [95% CI] 0.455 [0.350, 0.593]. (p<0.0001). Conclusions: The study showed that in routine clinical practice ataluren plus SoC significantly delayed age at LOA compared with SoC alone in patients with nmDMD.