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

Topic:

Other

Poster Number: 99

Author(s):

Pannie Trifillis, PTC Therapeutics Inc., South Plainfield, NJ, USA, Már Tulinius, MD, Department of Pediatrics, Gothenburg University, Queen Silvia Children’s Hospital, Sweden, Filippo Buccella, Parent Project APS, Rome, Italy, Isabelle Desguerre, Hôpital Necker – Enfants Malades, Paris, France, Janbernd Kirschner, MD, Medical Center-University of Freiburg; University Hospital Bonn, Faculty of Medicine, Eugenio Mercuri, Paediatric Neurology and Centro Clinico Nemo, Catholic University and Policlinico Gemelli, Fondazion, Francesco Muntoni, MD, Great Ormond Street Institute of Child Health, London, UK, Andres Nascimento-Osorio, MD, Hospital Sant Joan de Déu, Unidad de Patología Neuromuscular, Universidad de Barcelona, Spain, Shelley Johnson, DBA, MBA, PTC Therapeutics Inc., South Plainfield, NJ, USA, Christian Werner, PhD, PTC Therapeutics Germany GmbH, Frankfurt, Germany, Allan Kristensen, PhD, PTC Therapeutics Inc., South Plainfield, NJ, USA, Joel Jiang, PhD, PTC Therapeutics Inc., South Plainfield, NJ, USA, James Li, PTC Therapeutics Inc., South Plainfield, NJ, USA, Rich Able, PhD, PTC Therapeutics, Claudio L. Santos, MD, MBA, PTC Therapeutics Inc., South Plainfield, NJ, USA, Craig McDonald, MD, UC David Health

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 investigated if 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, 2021. Propensity score matching identified STRIDE and CINRG patient cohorts (N=241) 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 <30%.

Results: The mean (standard deviation) ages at onset of first symptoms (STRIDE vs CINRG; N=241 per cohort) were 2.7 (1.7) and 2.8 (1.5) years, respectively. Most patients (STRIDE vs CINRG) received corticosteroids for ?12 months (79.7% per cohort), with a similar proportion receiving deflazacort (43.6% vs 45.2%) or other corticosteroids (41.5% vs 43.2%). Median (95% confidence interval [CI]) ages at % predicted FVC <60% (STRIDE vs CINRG) were 17.6 (16.2, non-estimable) and 15.8 (15.1, 16.5) years, respectively (p=0.0051). Median (95% CI) ages at % predicted FVC <30% were non-estimable for STRIDE patients (only 0.5% [1/192] of patients reached % predicted FVC <30%) and 25.4 (20.6, 29.4) years for CINRG patients (p=0.0085).

Conclusions: These interim registry data suggest that treatment with ataluren and SoC in routine clinical practice slows disease progression in nmDMD patients.