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

Craig Campbell; Richard J. Barohn; Enrico Bertini; Brigitte Chabrol; Giacomo Pietro Comi; Basil T. Darras; Richard S. Finkel; Kevin M. Flanigan; Nathalie Goemans; Susan T. Iannaccone; Kristi J. Jones; Janbernd Kirschner; Jean K. Mah; Katherine D. Mathews; Craig M. McDonald; Eugenio Mercuri; Yoram Nevo; Yann Péreón; J. Ben Renfroe; Monique M. Ryan; Jacinda B. Sampson; Ulrike Schara; Thomas Sejersen; Kathryn Selby; Már Tulinius; Juan J. Vílchez; Thomas Voit; Lee Jen Wei; Brenda L. Wong; Gary Elfring; Marcio Souza; Joseph McIntosh; Panayiota Trifillis; Stuart W. Peltz; Francesco Muntoni

doi:10.2217/cer-2020-0095

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

Craig Campbell, Richard J. Barohn, Enrico Bertini, Brigitte Chabrol, Giacomo Pietro Comi, Basil T. Darras, Richard S. Finkel, Kevin M. Flanigan, Nathalie Goemans, Susan T. Iannaccone, Kristi J. Jones, Janbernd Kirschner, Jean K. Mah, Katherine D. Mathews, Craig M. McDonald, Eugenio Mercuri, Yoram Nevo, Yann Péreón, J. Ben Renfroe, Monique M. RyanJacinda B. Sampson, Ulrike Schara, Thomas Sejersen, Kathryn Selby, Már Tulinius, Juan J. Vílchez, Thomas Voit, Lee Jen Wei, Brenda L. Wong, Gary Elfring, Marcio Souza, Joseph McIntosh, Panayiota Trifillis, Stuart W. Peltz, Francesco Muntoni

Research output: Contribution to journal › Review article › peer-review

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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.

Original language	English (US)
Pages (from-to)	973-984
Number of pages	12
Journal	Journal of Comparative Effectiveness Research
Volume	9
Issue number	14
DOIs	https://doi.org/10.2217/cer-2020-0095
State	Published - Oct 2020

Keywords

6-minute walk distance
Duchenne muscular dystrophy
ataluren
efficacy
meta-analyses
nonsense mutation Duchenne muscular dystrophy
randomized controlled trials

ASJC Scopus subject areas

Health Policy

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Campbell, C., Barohn, R. J., Bertini, E., Chabrol, B., Comi, G. P., Darras, B. T., Finkel, R. S., Flanigan, K. M., Goemans, N., Iannaccone, S. T., Jones, K. J., Kirschner, J., Mah, J. K., Mathews, K. D., McDonald, C. M., Mercuri, E., Nevo, Y., Péreón, Y., Renfroe, J. B., ... Muntoni, F. (2020). Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy. Journal of Comparative Effectiveness Research, 9(14), 973-984. https://doi.org/10.2217/cer-2020-0095

Campbell, C, Barohn, RJ, Bertini, E, Chabrol, B, Comi, GP, Darras, BT, Finkel, RS, Flanigan, KM, Goemans, N, Iannaccone, ST, Jones, KJ, Kirschner, J, Mah, JK, Mathews, KD, McDonald, CM, Mercuri, E, Nevo, Y, Péreón, Y, Renfroe, JB, Ryan, MM, Sampson, JB, Schara, U, Sejersen, T, Selby, K, Tulinius, M, Vílchez, JJ, Voit, T, Wei, LJ, Wong, BL, Elfring, G, Souza, M, McIntosh, J, Trifillis, P, Peltz, SW & Muntoni, F 2020, 'Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy', Journal of Comparative Effectiveness Research, vol. 9, no. 14, pp. 973-984. https://doi.org/10.2217/cer-2020-0095

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title = "Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy",

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.",

keywords = "6-minute walk distance, Duchenne muscular dystrophy, ataluren, efficacy, meta-analyses, nonsense mutation Duchenne muscular dystrophy, randomized controlled trials",

author = "Craig Campbell and Barohn, {Richard J.} and Enrico Bertini and Brigitte Chabrol and Comi, {Giacomo Pietro} and Darras, {Basil T.} and Finkel, {Richard S.} and Flanigan, {Kevin M.} and Nathalie Goemans and Iannaccone, {Susan T.} and Jones, {Kristi J.} and Janbernd Kirschner and Mah, {Jean K.} and Mathews, {Katherine D.} and McDonald, {Craig M.} and Eugenio Mercuri and Yoram Nevo and Yann P{\'e}re{\'o}n and Renfroe, {J. Ben} and Ryan, {Monique M.} and Sampson, {Jacinda B.} and Ulrike Schara and Thomas Sejersen and Kathryn Selby and M{\'a}r Tulinius and V{\'i}lchez, {Juan J.} and Thomas Voit and Wei, {Lee Jen} and Wong, {Brenda L.} and Gary Elfring and Marcio Souza and Joseph McIntosh and Panayiota Trifillis and Peltz, {Stuart W.} and Francesco Muntoni",

note = "Publisher Copyright: {\textcopyright} 2020 Campbell C et al.",

year = "2020",

month = oct,

doi = "10.2217/cer-2020-0095",

language = "English (US)",

volume = "9",

pages = "973--984",

journal = "Journal of Comparative Effectiveness Research",

issn = "2042-6305",

publisher = "Future Medicine Ltd.",

number = "14",

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TY - JOUR

T1 - Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy

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 - Péreón, 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

Y1 - 2020/10

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 - Duchenne muscular dystrophy

KW - ataluren

KW - efficacy

KW - meta-analyses

KW - nonsense mutation Duchenne muscular dystrophy

KW - randomized controlled trials

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DO - 10.2217/cer-2020-0095

M3 - Review article

C2 - 32851872

AN - SCOPUS:85092802001

SN - 2042-6305

VL - 9

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JO - Journal of Comparative Effectiveness Research

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ER -

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

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