Safety and effectiveness of ataluren in patients with nonsense mutation DMD in the STRIDE Registry compared with the CINRG Duchenne Natural History Study (2015-2022): 2022 interim analysis.

Autor: Mercuri E; Department of Pediatric Neurology, Catholic University, Rome, Italy. eugeniomaria.mercuri@unicatt.it.; Centro Clinico Nemo, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy. eugeniomaria.mercuri@unicatt.it., Osorio AN; Neuromuscular Unit, Department of Neurology and Research in Neuromuscular Diseases, Institut de Recerca Sant Joan de Déu, Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain., Muntoni F; UCL Great Ormond Street Institute of Child Health, London, UK.; National Institute for Health Research, Great Ormond Street Institute of Child Health Biomedical Research Centre, University College London, London, UK., Buccella F; Parent Project APS, Rome, Italy., Desguerre I; Hôpital Necker-Enfants Malades, Paris, France., Kirschner J; Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany., Tulinius M; Department of Pediatrics, Gothenburg University, Queen Silvia Children's Hospital, Gothenburg, Sweden., de Resende MBD; Department of Neurology, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil., Morgenroth LP; Therapeutic Research in Neuromuscular Disorders Solutions (TRiNDS), Pittsburgh, PA, USA., Gordish-Dressman H; Center for Genetic Medicine, Children's National Health System and the George Washington, Washington, DC, USA., Johnson S; PTC Therapeutics Inc., South Plainfield, NJ, USA., Kristensen A; PTC Therapeutics Inc., South Plainfield, NJ, USA., Werner C; PTC Therapeutics Germany GmbH, Frankfurt, Germany., Trifillis P; PTC Therapeutics Inc., South Plainfield, NJ, USA., Henricson EK; University of California Davis School of Medicine, Davis, CA, USA., McDonald CM; University of California Davis School of Medicine, Davis, CA, USA.
Jazyk: angličtina
Zdroj: Journal of neurology [J Neurol] 2023 Aug; Vol. 270 (8), pp. 3896-3913. Date of Electronic Publication: 2023 Apr 28.
DOI: 10.1007/s00415-023-11687-1
Abstrakt: Objective: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, international, multicenter registry of real-world ataluren use in individuals with nonsense mutation Duchenne muscular dystrophy (nmDMD) in clinical practice. This updated interim report (data cut-off: January 31, 2022), describes STRIDE patient characteristics and ataluren safety data, as well as the effectiveness of ataluren plus standard of care (SoC) in STRIDE versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS).
Methods: Patients are followed up from enrollment for at least 5 years or until study withdrawal. Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established predictors of disease progression.
Results: As of January 31, 2022, 307 patients were enrolled from 14 countries. Mean (standard deviation [SD]) ages at first symptoms and at genetic diagnosis were 2.9 (1.7) years and 4.5 (3.7) years, respectively. Mean (SD) duration of ataluren exposure was 1671 (56.8) days. Ataluren had a favorable safety profile; most treatment-emergent adverse events were mild or moderate and unrelated to ataluren. Kaplan-Meier analyses demonstrated that ataluren plus SoC significantly delayed age at loss of ambulation by 4 years (p < 0.0001) and age at decline to %-predicted forced vital capacity of < 60% and < 50% by 1.8 years (p = 0.0021) and 2.3 years (p = 0.0207), respectively, compared with SoC alone.
Conclusion: Long-term, real-world treatment with ataluren plus SoC delays several disease progression milestones in individuals with nmDMD. NCT02369731; registration date: February 24, 2015.
(© 2023. The Author(s).)
Databáze: MEDLINE
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