Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy

• Published in: Journal of comparative effectiveness research Vol. 9; no. 14; pp. 973 - 984
• Main Authors: Campbell, Craig, Barohn, Richard J, Bertini, Enrico, Chabrol, Brigitte, Comi, Giacomo Pietro, Darras, Basil T, Finkel, Richard S, Flanigan, Kevin M, Goemans, Nathalie, Iannaccone, Susan T, Jones, Kristi J, Kirschner, Janbernd, Mah, Jean K, Mathews, Katherine D, McDonald, Craig M, Mercuri, Eugenio, Nevo, Yoram, Péréon, Yann, Renfroe, J Ben, Ryan, Monique M, Sampson, Jacinda B, Schara, Ulrike, Sejersen, Thomas, Selby, Kathryn, Tulinius, Már, Vílchez, Juan J, Voit, Thomas, Wei, Lee-Jen, Wong, Brenda L, Elfring, Gary, Souza, Marcio, McIntosh, Joseph, Trifillis, Panayiota, Peltz, Stuart W, Muntoni, Francesco
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.10.2020
• Subjects: 6-minute walk distance; 6-minute walk test; Annan medicin och hälsovetenskap; ataluren; Clinical trials; Codon, Nonsense - genetics; controlled trials; Demographics; Duchenne muscular dystrophy; efficacy; end-points; Health Care Sciences & Services; Humans; meta-analyses; Meta-analysis; multicenter; Muscular dystrophy; Muscular Dystrophy, Duchenne - drug therapy; Muscular Dystrophy, Duchenne - genetics; Mutation; nonsense mutation Duchenne muscular dystrophy; Other Medical and Health Sciences; Oxadiazoles - therapeutic use; Patients; randomized; randomized controlled trials; Randomized Controlled Trials as Topic; Statistical analysis; Ukraine; nonsense mutation Duchenne muscular dystrophy; meta-analyses; Duchenne muscular dystrophy; ataluren; 6-minute walk distance; randomized controlled trials; efficacy
• ISSN: 2042-6305; 2042-6313; 2042-6313
• DOI: 10.2217/cer-2020-0095

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.