Survival among patients receiving eteplirsen for up to 8 years for the treatment of Duchenne muscular dystrophy and contextualization with natural history controls.

Autor: Iff J; Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA., Done N; Analysis Group, Inc., Boston, Massachusetts, USA., Tuttle E; Analysis Group, Inc., Boston, Massachusetts, USA., Zhong Y; Analysis Group, Inc., Boston, Massachusetts, USA., Wei F; Analysis Group, Inc., Boston, Massachusetts, USA., Darras BT; Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA., McDonald CM; University of California Davis Health System, Sacramento, California, USA., Mercuri E; Paediatric Neurology and Centro Clinico NeMO, Catholic University and Policlinico Gemelli, Fondazione Policlinico Universitario Agostino Gemelli IRCSS, Rome, Italy.; Centro Clinico NeMO, Fondazione Policlinico Universitario Agostino Gemelli IRCSS, Rome, Italy., Muntoni F; Dubowitz Neuromuscular Centre, UCL Institute of Child Health and Great Ormond Street Hospital for Children, London, UK.; Great Ormond Street Hospital, London, UK.; NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.
Jazyk: angličtina
Zdroj: Muscle & nerve [Muscle Nerve] 2024 Jul; Vol. 70 (1), pp. 60-70. Date of Electronic Publication: 2024 Mar 14.
DOI: 10.1002/mus.28075
Abstrakt: Introduction/aims: Eteplirsen, approved in the US for patients with Duchenne muscular dystrophy (DMD) with exon 51 skip-amenable variants, is associated with attenuated ambulatory/pulmonary decline versus DMD natural history (NH). We report overall survival in a US cohort receiving eteplirsen and contextualize these outcomes versus DMD NH.
Methods: US patients with DMD receiving eteplirsen were followed through a patient support program, with data collected on ages at eteplirsen initiation and death/end of follow-up. Individual DMD NH data were extracted by digitizing Kaplan-Meier (KM) curves from published systematic and targeted literature reviews. Overall survival age was analyzed using KM curves and contextualized with DMD NH survival curves; subanalyses considered age groups and duration of eteplirsen exposure. Overall survival time from treatment initiation was also evaluated.
Results: A total of 579 eteplirsen-treated patients were included. During a total follow-up of 2119 person-years, median survival age was 32.8 years. DMD NH survival curves extracted from four publications (follow-up for 1224 DMD NH controls) showed overall pooled median survival age of 27.4 years. Eteplirsen-treated patients had significantly longer survival from treatment initiation versus age-matched controls (age-adjusted hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.44-0.98; p < .05). Longer treatment exposure was associated with improved survival (HR, 0.15; 95% CI, 0.05-0.41; p < .001). Comparisons using different DMD NH cohorts to address common risks of bias yielded consistent findings.
Discussion: Data suggest eteplirsen may prolong survival in patients with DMD across a wide age range. As more data become available, the impact of eteplirsen on survival will be further elucidated.
(© 2024 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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