Craig Campbell1, Richard J Barohn2, Enrico Bertini3, Brigitte Chabrol4, Giacomo Pietro Comi5, Basil T Darras6, Richard S Finkel7,8, Kevin M Flanigan9, Nathalie Goemans10, Susan T Iannaccone11, Kristi J Jones12, Janbernd Kirschner13, Jean K Mah14, Katherine D Mathews15, Craig M McDonald16, Eugenio Mercuri17, Yoram Nevo18, Yann Péréon19, J Ben Renfroe20, Monique M Ryan21, Jacinda B Sampson22, Ulrike Schara23, Thomas Sejersen24, Kathryn Selby25, Már Tulinius26, Juan J Vílchez27, Thomas Voit28, Lee-Jen Wei29, Brenda L Wong30, Gary Elfring31, Marcio Souza31, Joseph McIntosh31, Panayiota Trifillis31, Stuart W Peltz31, Francesco Muntoni28. 1. Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5C1, Canada. 2. University of Kansas Medical Center, Kansas City, KS 66160, USA. 3. Bambino Gesù Children's Research Hospital, Rome, 00146, Italy. 4. Hôpital de la Timone, Unité de Médecine Infantile, Marseille, 13385, France. 5. IRCCS Fondazione Ca'Granda Ospedale Maggiore Policlinico, Dino Ferrari Centre, Department of Pathophysiology & Transplantation, University of Milan, Milan, 20122, Italy. 6. Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. 7. Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. 8. St. Jude Children's Research Hospital, Memphis, TN 38105, USA. 9. Nationwide Children's Hospital, Columbus, OH 43205, USA. 10. University Hospitals Leuven, KU Leuven, Leuven, 3000, Belgium. 11. University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 12. Kids Neuroscience, The Children's Hospital at Westmead, Westmead, NSW, 2145, Australia. 13. Department of Neuropediatrics & Muscle Disorders, Medical Center, University of Freiburg, Freiburg 79110, Germany. 14. Department of Pediatrics, Division of Pediatric Neurology, Alberta Children's Hospital, University of Calgary, Calgary, AB T3B 6A8, Canada. 15. Departments of Pediatrics & Neurology, Division of Pediatric Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. 16. University of California Davis Health, Sacramento, CA 95817, USA. 17. Department of Pediatric Neurology, Catholic University, Rome, 00168, Italy. 18. Schneider Children's Medical Center, Tel Aviv University, Tel Aviv, 6997801, Israel. 19. Reference Centre for Neuromuscular Disorders AOC, Hôtel-Dieu, Nantes, 44000, France. 20. Child Neurology Center of Northwest Florida, Gulf Breeze, FL 32561, USA. 21. The Royal Children's Hospital, Parkville, Victoria, 3052, Australia. 22. Stanford University Medical Center, Department of Neurology & Neurological Sciences, Stanford, CA 94305, USA. 23. Department of Pediatric Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, 45122, Germany. 24. Karolinska University Hospital, Karolinska Institutet, Stockholm, 171 76, Sweden. 25. Division of Neurology, British Columbia Children's Hospital, Vancouver, BC, V6H 3N1, Canada. 26. Gothenburg University, Queen Silvia Children's Hospital, Gothenburg, 416 85, Sweden. 27. Hospital Universitario y Politécnico La Fe, CIBERER, Valencia, 46026, Spain. 28. 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. 29. Harvard TH Chan School of Public Health, Harvard University, Boston, MA 02115, USA. 30. University of Massachusetts Medical School, UMass, Worcester, MA 01655, USA. 31. PTC Therapeutics Inc., South Plainfield, NJ 07080, USA.
Abstract
Aim: Assess the totality of efficacy evidence for ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). Materials & methods: 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. Results: 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. Conclusion: 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.
Aim: Assess the totality of efficacy evidence for ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). Materials & methods: 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. Results: 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. Conclusion: 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.
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