Journal article
Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy
Journal of comparative effectiveness research, Vol.9(14), pp.973-984
10/2020
DOI: 10.2217/cer-2020-0095
PMID: 32851872
Abstract
Assess the totality of efficacy evidence for ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD).
Data from the two completed randomized controlled trials (ClinicalTrials.gov: NCT00592553; NCT01826487) of ataluren in nmDMD were combined to examine the intent-to-treat (ITT) populations and two patient subgroups (baseline 6-min walk distance [6MWD] ≥300-<400 or <400 m). Meta-analyses examined 6MWD change from baseline to week 48.
Statistically significant differences in 6MWD change with ataluren versus placebo were observed across all three meta-analyses. Least-squares mean difference (95% CI): ITT (n = 342), +17.2 (0.2-34.1) m, p = 0.0473; ≥300-<400 m (n = 143), +43.9 (18.2-69.6) m, p = 0.0008; <400 m (n = 216), +27.7 (6.4-49.0) m, p = 0.0109.
These meta-analyses support previous evidence for ataluren in slowing disease progression versus placebo in patients with nmDMD over 48 weeks. Treatment benefit was most evident in patients with a baseline 6MWD ≥300-<400 m (the ambulatory transition phase), thereby informing future trial design.
Details
- Title: Subtitle
- Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy
- Creators
- Craig Campbell - Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5C1, CanadaRichard J Barohn - University of Kansas Medical Center, Kansas City, KS 66160, USAEnrico Bertini - Bambino Gesù Children's Research Hospital, Rome, 00146, ItalyBrigitte Chabrol - Hôpital de la Timone, Unité de Médecine Infantile, Marseille, 13385, FranceGiacomo Pietro Comi - IRCCS Fondazione Ca'Granda Ospedale Maggiore Policlinico, Dino Ferrari Centre, Department of Pathophysiology & Transplantation, University of Milan, Milan, 20122, ItalyBasil T Darras - Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USARichard S Finkel - St. Jude Children's Research Hospital, Memphis, TN 38105, USAKevin M Flanigan - Nationwide Children's Hospital, Columbus, OH 43205, USANathalie Goemans - University Hospitals Leuven, KU Leuven, Leuven, 3000, BelgiumSusan T Iannaccone - University of Texas Southwestern Medical Center, Dallas, TX 75390, USAKristi J Jones - Kids Neuroscience, The Children's Hospital at Westmead, Westmead, NSW, 2145, AustraliaJanbernd Kirschner - Department of Neuropediatrics & Muscle Disorders, Medical Center, University of Freiburg, Freiburg 79110, GermanyJean K Mah - Department of Pediatrics, Division of Pediatric Neurology, Alberta Children's Hospital, University of Calgary, Calgary, AB T3B 6A8, CanadaKatherine D Mathews - Departments of Pediatrics & Neurology, Division of Pediatric Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USACraig M McDonald - University of California Davis Health, Sacramento, CA 95817, USAEugenio Mercuri - Department of Pediatric Neurology, Catholic University, Rome, 00168, ItalyYoram Nevo - Schneider Children's Medical Center, Tel Aviv University, Tel Aviv, 6997801, IsraelYann Péréon - Reference Centre for Neuromuscular Disorders AOC, Hôtel-Dieu, Nantes, 44000, FranceJ Ben Renfroe - Child Neurology Center of Northwest Florida, Gulf Breeze, FL 32561, USAMonique M Ryan - The Royal Children's Hospital, Parkville, Victoria, 3052, AustraliaJacinda B Sampson - Stanford University Medical Center, Department of Neurology & Neurological Sciences, Stanford, CA 94305, USAUlrike Schara - Department of Pediatric Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, 45122, GermanyThomas Sejersen - Karolinska University Hospital, Karolinska Institutet, Stockholm, 171 76, SwedenKathryn Selby - Division of Neurology, British Columbia Children's Hospital, Vancouver, BC, V6H 3N1, CanadaMár Tulinius - Gothenburg University, Queen Silvia Children's Hospital, Gothenburg, 416 85, SwedenJuan J Vílchez - Hospital Universitario y Politécnico La Fe, CIBERER, Valencia, 46026, SpainThomas Voit - NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London & UCL Great Ormond Street Institute of Child Health, Great Ormond Street Hospital Trust, London, WC1N 1EH, UKLee-Jen Wei - Harvard TH Chan School of Public Health, Harvard University, Boston, MA 02115, USABrenda L Wong - University of Massachusetts Medical School, UMass, Worcester, MA 01655, USAGary Elfring - PTC Therapeutics Inc., South Plainfield, NJ 07080, USAMarcio Souza - PTC Therapeutics Inc., South Plainfield, NJ 07080, USAJoseph McIntosh - PTC Therapeutics Inc., South Plainfield, NJ 07080, USAPanayiota Trifillis - PTC Therapeutics Inc., South Plainfield, NJ 07080, USAStuart W Peltz - PTC Therapeutics Inc., South Plainfield, NJ 07080, USAFrancesco Muntoni - NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London & UCL Great Ormond Street Institute of Child Health, Great Ormond Street Hospital Trust, London, WC1N 1EH, UK
- Resource Type
- Journal article
- Publication Details
- Journal of comparative effectiveness research, Vol.9(14), pp.973-984
- DOI
- 10.2217/cer-2020-0095
- PMID
- 32851872
- NLM abbreviation
- J Comp Eff Res
- ISSN
- 2042-6305
- eISSN
- 2042-6313
- Publisher
- England
- Grant note
- DOI: 10.13039/100013223, name: PTC Therapeutics
- Language
- English
- Date published
- 10/2020
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984070210802771
Metrics
18 Record Views