TY - JOUR
T1 - Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy
AU - PTC124-GD-007-DMD Study Group
AU - ACT DMD Study Group
AU - Clinical Evaluator Training Groups
AU - Campbell, Craig
AU - Barohn, Richard J.
AU - Bertini, Enrico
AU - Chabrol, Brigitte
AU - Comi, Giacomo Pietro
AU - Darras, Basil T.
AU - Finkel, Richard S.
AU - Flanigan, Kevin M.
AU - Goemans, Nathalie
AU - Iannaccone, Susan T.
AU - Jones, Kristi J.
AU - Kirschner, Janbernd
AU - Mah, Jean K.
AU - Mathews, Katherine D.
AU - McDonald, Craig M.
AU - Mercuri, Eugenio
AU - Nevo, Yoram
AU - Péréon, Yann
AU - Renfroe, J. Ben
AU - Ryan, Monique M.
AU - Sampson, Jacinda B.
AU - Schara, Ulrike
AU - Sejersen, Thomas
AU - Selby, Kathryn
AU - Tulinius, Már
AU - Vílchez, Juan J.
AU - Voit, Thomas
AU - Wei, Lee Jen
AU - Wong, Brenda L.
AU - Elfring, Gary
AU - Souza, Marcio
AU - McIntosh, Joseph
AU - Trifillis, Panayiota
AU - Peltz, Stuart W.
AU - Muntoni, Francesco
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
KW - 6-minute walk distance
KW - ataluren
KW - Duchenne muscular dystrophy
KW - efficacy
KW - meta-analyses
KW - nonsense mutation Duchenne muscular dystrophy
KW - randomized controlled trials
UR - http://www.scopus.com/inward/record.url?scp=85092802001&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092802001&partnerID=8YFLogxK
U2 - 10.2217/cer-2020-0095
DO - 10.2217/cer-2020-0095
M3 - Article
C2 - 32851872
AN - SCOPUS:85092802001
VL - 9
SP - 973
EP - 984
JO - Journal of Comparative Effectiveness Research
JF - Journal of Comparative Effectiveness Research
SN - 2042-6305
IS - 14
ER -