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.
Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy / C. Campbell, R.J. Barohn, E. Bertini, B. Chabrol, G.P. Comi, B.T. Darras, R.S. Finkel, K.M. Flanigan, N. Goemans, S.T. Iannaccone, K.J. Jones, J. Kirschner, J.K. Mah, K.D. Mathews, C.M. McDonald, E. Mercuri, Y. Nevo, Y. Péréon, J.B. Renfroe, M.M. Ryan, J.B. Sampson, U. Schara, T. Sejersen, K. Selby, M. Tulinius, J.J. Vílchez, T. Voit, L. Wei, B.L. Wong, G. Elfring, M. Souza, J. McIntosh, P. Trifillis, S.W. Peltz, F. Muntoni. - In: JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH. - ISSN 2042-6305. - 9:14(2020 Oct), pp. 973-984.
Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy
G.P. Comi;
2020
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.
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