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

被引：42

作者：

Campbell, Craig ^{[1
]}

Barohn, Richard J. ^{[2
]}

Bertini, Enrico ^{[3
]}

Chabrol, Brigitte ^{[4
]}

Comi, Giacomo Pietro ^{[5
]}

Darras, Basil T. ^{[6
]}

Finkel, Richard S. ^{[7
,8
]}

Flanigan, Kevin M. ^{[9
]}

Goemans, Nathalie ^{[10
]}

Iannaccone, Susan T. ^{[11
]}

Jones, Kristi J. ^{[12
]}

Kirschner, Janbernd ^{[13
]}

Mah, Jean K. ^{[14
]}

Mathews, Katherine D. ^{[15
,16
]}

McDonald, Craig M. ^{[17
]}

Mercuri, Eugenio ^{[18
]}

Nevo, Yoram ^{[19
]}

Pereon, Yann ^{[20
]}

Ben Renfroe, J. ^{[21
]}

Ryan, Monique M. ^{[22
]}

Sampson, Jacinda B. ^{[23
]}

Schara, Ulrike ^{[24
]}

Sejersen, Thomas ^{[25
]}

Selby, Kathryn ^{[26
]}

Tulinius, Mar ^{[27
]}

Vilchez, Juan J. ^{[28
]}

Voit, Thomas ^{[29
,30
]}

Wei, Lee-Jen ^{[31
]}

Wong, Brenda L. ^{[32
]}

Elfring, Gary ^{[33
]}

Souza, Marcio ^{[33
]}

McIntosh, Joseph ^{[33
]}

Trifillis, Panayiota ^{[33
]}

Peltz, Stuart W. ^{[33
]}

Muntoni, Francesco ^{[29
,30
]}

机构：

[1] Western Univ, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada

[2] Univ Kansas, Med Ctr, Kansas City, KS 66160 USA

[3] Bambino Gesu Childrens Res Hosp, I-00146 Rome, Italy

[4] Hop La Timone, Unite Med Infantile, F-13385 Marseille, France

[5] Univ Milan, IRCCS Fdn Ca Granda Osped Maggiore Policlin, Dino Ferrari Ctr, Dept Pathophysiol & Transplantat, I-20122 Milan, Italy

[6] Harvard Med Sch, Boston Childrens Hosp, Boston, MA 02115 USA

[7] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[8] St Jude Childrens Res Hosp, Memphis, TN 38105 USA

[9] Nationwide Childrens Hosp, Columbus, OH 43205 USA

[10] Katholieke Univ Leuven, Univ Hosp Leuven, B-3000 Leuven, Belgium

[11] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA

[12] Childrens Hosp Westmead, Kids Neurosci, Westmead, NSW 2145, Australia

[13] Univ Freiburg, Med Ctr, Dept Neuropediat & Muscle Disorders, D-79110 Freiburg, Germany

[14] Univ Calgary, Alberta Childrens Hosp, Dept Pediat, Div Pediat Neurol, Calgary, AB T3B 6A8, Canada

[15] Univ Iowa, Dept Pediat, Div Pediat Neurol, Carver Coll Med, Iowa City, IA 52242 USA

[16] Univ Iowa, Dept Neurol, Div Pediat Neurol, Carver Coll Med, Iowa City, IA 52242 USA

[17] Univ Calif Davis Hlth, Sacramento, CA 95817 USA

[18] Catholic Univ, Dept Pediat Neurol, I-00168 Rome, Italy

[19] Tel Aviv Univ, Schneider Childrens Med Ctr, IL-6997801 Tel Aviv, Israel

[20] Hop Hotel Dieu, Reference Ctr Neuromuscular Disorders AOC, F-44000 Nantes, France

[21] Child Neurol Ctr Northwest Florida, Gulf Breeze, FL 32561 USA

[22] Royal Childrens Hosp, Parkville, Vic 3052, Australia

[23] Stanford Univ, Dept Neurol & Neurol Sci, Med Ctr, Stanford, CA 94305 USA

[24] Univ Duisburg Essen, Univ Hosp Essen, Dept Pediat Neurol, D-45122 Essen, Germany

[25] Karolinska Inst, Karolinska Univ Hosp, S-17176 Stockholm, Sweden

[26] British Columbia Childrens Hosp, Div Neurol, Vancouver, BC V6H 3N1, Canada

[27] Gothenburg Univ, Queen Silvia Childrens Hosp, S-41685 Gothenburg, Sweden

[28] Hosp Univ & Politecn La Fe, CIBERER, Valencia 46026, Spain

[29] UCL, NIHR Great Ormond St Hosp Biomed Res Ctr, London WC1N 1EH, England

[30] Great Ormond St Hosp Trust, UCL Great Ormond St Inst Child Hlth, London WC1N 1EH, England

[31] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA

[32] Univ Massachusetts, UMass, Med Sch, Worcester, MA 01655 USA

[33] PTC Therapeut Inc, South Plainfield, NJ 07080 USA

来源：

JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH | 2020年 / 9卷 / 14期

基金：

美国国家卫生研究院;

关键词：

6-minute walk distance; ataluren; Duchenne muscular dystrophy; efficacy; meta-analyses; nonsense mutation Duchenne muscular dystrophy; randomized controlled trials; 6-MINUTE WALK TEST; END-POINTS; MULTICENTER;

D O I：

10.2217/cer-2020-0095

中图分类号：

R19 [保健组织与事业（卫生事业管理）];

学科分类号：

100404 [儿少卫生与妇幼保健学];

摘要：

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.

引用

页码：973 / 984

页数：12

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