Abstract
Aim: Compare efficacies of deflazacort and prednisone/prednisolone in providing clinically meaningful delays in loss of physical milestones in patients with nonsense mutation Duchenne muscular dystrophy. Materials & methods: Placebo data from Phase IIb (ClinicalTrials.gov Identifier: NCT00592553) and ACT DMD (ClinicalTrials.gov Identifier: NCT01826487) ataluren nonsense mutation Duchenne muscular dystrophy clinical trials were retrospectively combined in meta-analyses (intent-to-treat population; for change from baseline to week 48 in 6-min walk distance [6MWD] and timed function tests). Results: Significant improvements in change in 6-min walk distance with deflazacort versus prednisone/prednisolone (least-squares mean difference 39.54 m [95% CI: 13.799, 65.286; p = 0.0026]). Significant and clinically meaningful improvements in 4-stair climb and 4-stair descend for deflazacort versus prednisone/prednisolone. Conclusion: Deflazacort provides clinically meaningful delays in loss of physical milestones over 48 weeks compared with prednisone/prednisolone for patients with nonsense mutation Duchenne muscular dystrophy.
| Original language | English |
|---|---|
| Pages (from-to) | 1337-1347 |
| Number of pages | 11 |
| Journal | Journal of Comparative Effectiveness Research |
| Volume | 10 |
| Issue number | 18 |
| DOIs | |
| State | Published - Dec 1 2021 |
Keywords
- Duchenne muscular dystrophy
- deflazacort
- meta-analysis
- nonsense mutation Duchenne muscular dystrophy
- prednisolone
- prednisone
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In: Journal of Comparative Effectiveness Research, Vol. 10, No. 18, 01.12.2021, p. 1337-1347.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Meta-analyses of deflazacort versus prednisone/prednisolone in patients with nonsense mutation Duchenne muscular dystrophy
AU - Shieh, Perry B.
AU - Elfring, Gary
AU - Trifillis, Panayiota
AU - Santos, Claudio
AU - Peltz, Stuart W.
AU - Parsons, Julie A.
AU - Apkon, Susan
AU - Darras, Basil T.
AU - Campbell, Craig
AU - McDonald, Craig M.
AU - Barohn, Richard J.
AU - Bertini, Enrico
AU - Bushby, Kate
AU - Chabrol, Brigitte
AU - Ciafaloni, Emma
AU - Columer, Jaume
AU - Comi, Giacomi Pietro
AU - Connolly, Anne
AU - Finkel, Richard S.
AU - Flanigan, Kevin M.
AU - Goemans, Nathalie
AU - Guglieri, Michela
AU - Iannaccone, Susan T.
AU - Jones, Kristi J.
AU - Kaufmann, Petra
AU - Kirschner, Janbernd
AU - Mah, Jean K.
AU - Mathews, Katherine
AU - Mercuri, Eugenio
AU - Muntoni, Francesco
AU - Nevo, Yoram
AU - Osorio, Andrés Nascimento
AU - Péréon, Yann
AU - Quinlivan, Rosaline
AU - Renfroe, J. Ben
AU - Russman, Barry
AU - Ryan, Monique
AU - Sampson, Jacinda
AU - Schara, Ulrike
AU - Selby, Kathryn
AU - Sejersen, Thomas
AU - Sproule, Douglas M.
AU - Sweeney, H. Lee
AU - Tulinius, Már
AU - Vilchez, Juan J.
AU - Vita, Giuseppe
AU - Voit, Thomas
AU - Burns-Wechsler, Stephanie
AU - Wong, Brenda
AU - Abresch, Ted
AU - Henricson, Erik K.
AU - Coleman, Kim
AU - Eagle, Michelle
AU - Florence, Julaine
AU - Gappmaier, Ed
AU - McDonald, Craig
AU - Abdel-Hamid, Hoda Z.
AU - Barohn, Richard J.
AU - Bertini, Enrico
AU - Bloetzer, Clemens
AU - Bushby, Kate
AU - Butterfield, Russell J.
AU - Chabrol, Brigitte
AU - Chae, Jong Hee
AU - Comi, Giacomi Pietro
AU - Dastgir, Jahannaz
AU - Desguerre, Isabelle
AU - Escobar, Raul G.
AU - Finanger, Erika
AU - Finkel, Richard S.
AU - Goemans, Nathalie
AU - Guglieri, Michela
AU - Heydemann, Peter
AU - Hughes, Imelda
AU - Iannaccone, Susan T.
AU - Jones, Kristi J.
AU - Kaminska, Anna
AU - Karachunski, Peter
AU - Kirschner, Janbernd
AU - Kudr, Martin
AU - Lotze, Timothy
AU - Mah, Jean K.
AU - Mathews, Katherine
AU - Muntoni, Francesco
AU - Nevo, Yoram
AU - Osorio, Andrés Nascimento
AU - Péréon, Yann
AU - De Queiroz Campos Araujo, Alexandra Prufer
AU - Renfroe, J. Ben
AU - Dutra De Resende, Maria Bernadete
AU - Ryan, Monique
AU - Sampson, Jacinda
AU - Schara, Ulrike
AU - Selby, Kathryn
AU - Sejersen, Thomas
AU - Sweeney, H. Lee
AU - Tennekoon, Gihan
AU - Topaloglu, Haluk
AU - Torricelli, Ricardo Erazo
AU - Tulinius, Már
AU - Vilchez, Juan J.
AU - Vita, Giuseppe
AU - Voit, Thomas
AU - Wong, Brenda
AU - Alfano, Lindsay N.
AU - Eagle, Michelle
AU - James, Meredith K.
AU - Lowes, Linda
AU - Mayhew, Anna
AU - Mazzone, Elena S.
AU - Nelson, Leslie
AU - Rose, Kristy J.
N1 - Funding Information: Professional medical writing assistance was provided by A Skorupa of EnlightenMed, LLC, and Tove Anderson of PharmaGenesis London, and was funded by PTC Therapeutics, Inc. The authors provided the initial outline draft and worked with A Skorupa to produce the first full draft of this manuscript. Editorial support was provided by PharmaGenesis London, and was funded by PTC Therapeutics, Inc. Funding Information: This research was funded by PTC Therapeutics, Inc., and did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. C Campbell has received grants from and has acted as a consultant to PTC Therapeutics, and has been a clinical trial investigator for Acceleron, AMO, Biogen, Biomarin, BMS, Catabasis, Cytokinetics, Pfizer, PTC Therapeutics, Sarepta, Wave and Roche. He did not receive any personal compensation for these activities. B Darras reports, for the last year, advisory boards for AveXis, Biogen, Cytokinetics, Dynacure, Genentech, Roche and Sarepta Therapeutics. Over the last 2 years, he has participated in advisory boards for AveXis, Biogen, Cytokinetics, Dynacure, Genentech, PTC Therapeutics, Roche and Sarepta Therapeutics. He has also received research support from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the Slaney Family Fund for SMA, the SMA Foundation and Working on Walking Fund; grants from Biogen, CureSMA and Ionis Pharmaceuticals, Inc. during CHERISH, CS2, CS11 and CS12 studies and ENDEAR, and also from AveXis, Cytokinetics, Fibrogen, PTC Therapeutics, Roche, Santhera Pharmaceuticals, Sarepta Therapeutics and Summit Therapeutics. He reports no personal financial interests in any of these companies. PB Shieh has served as an ad hoc advisory board member for AveXis, Biogen, Marathon, PTC Therapeutics and Sarepta Therapeutics, but he has no financial interests in these companies. He has received research support from Biogen and Ionis Pharmaceuticals for their SMA studies, as well as from BMS/Roche for their DMD/myostatin clinical trial, Cytokinetics for their SMA clinical trial, Pfizer for their DMD/myostatin clinical trial, PTC Therapeutics for their DMD/ataluren trial, Sanofi/Genzyme for their Pompe clinical trial, Sarepta Therapeutics for their DMD clinical trials and Summit Therapeutics for their DMD clinical trial. CM McDonald has served as a compensated consultant for clinical trials for PTC Therapeutics, and outside the submitted work as a consultant for Astellas, Biomarin, Capricor, Catabasis, Cytokinetics, Eli Lilly, Edgewise Therapeutics, Epirium Bio (formerly Cardero Therapeutics), FibroGen, Italfarmaco, Marathon, Pfizer, Santhera Pharmaceuticals and Sarepta Therapeutics. He serves on external advisory boards related to Duchenne muscular dystrophy with compensation from Capricor, Eli Lilly, PTC Therapeutics, Santhera Pharmaceuticals and Sarepta Therapeutics, and held grants from NIDILRR, Parent Project Muscular Dystrophy US, the US Department of Education/NIDRR, US NIH/NIAMS and the US Department of Defense during the time of the study. J Parsons has served as an ad hoc scientific advisory board member for AveXis, Biogen, Genentech and Sarepta Therapeutics. She has been a clinical investigator for PTC Therapeutics and Sarepta Therapeutics for their DMD clinical trials. She has no financial interests in these companies. S Apkon has served as a consultant for Biogen. She has received research support from BMS/Roche for their DMD/myostatin clinical trial, PTC Therapeutics for their DMD/ataluren trials and Sarepta Therapeutics for their DMD/eteplirsen clinical trials. She has not received personal payment for these activities. G Elfring, P Trifillis, C Santos and SW Peltz are employees and stockholders of PTC Therapeutics, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Publisher Copyright: © 2021 Shieh.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Aim: Compare efficacies of deflazacort and prednisone/prednisolone in providing clinically meaningful delays in loss of physical milestones in patients with nonsense mutation Duchenne muscular dystrophy. Materials & methods: Placebo data from Phase IIb (ClinicalTrials.gov Identifier: NCT00592553) and ACT DMD (ClinicalTrials.gov Identifier: NCT01826487) ataluren nonsense mutation Duchenne muscular dystrophy clinical trials were retrospectively combined in meta-analyses (intent-to-treat population; for change from baseline to week 48 in 6-min walk distance [6MWD] and timed function tests). Results: Significant improvements in change in 6-min walk distance with deflazacort versus prednisone/prednisolone (least-squares mean difference 39.54 m [95% CI: 13.799, 65.286; p = 0.0026]). Significant and clinically meaningful improvements in 4-stair climb and 4-stair descend for deflazacort versus prednisone/prednisolone. Conclusion: Deflazacort provides clinically meaningful delays in loss of physical milestones over 48 weeks compared with prednisone/prednisolone for patients with nonsense mutation Duchenne muscular dystrophy.
AB - Aim: Compare efficacies of deflazacort and prednisone/prednisolone in providing clinically meaningful delays in loss of physical milestones in patients with nonsense mutation Duchenne muscular dystrophy. Materials & methods: Placebo data from Phase IIb (ClinicalTrials.gov Identifier: NCT00592553) and ACT DMD (ClinicalTrials.gov Identifier: NCT01826487) ataluren nonsense mutation Duchenne muscular dystrophy clinical trials were retrospectively combined in meta-analyses (intent-to-treat population; for change from baseline to week 48 in 6-min walk distance [6MWD] and timed function tests). Results: Significant improvements in change in 6-min walk distance with deflazacort versus prednisone/prednisolone (least-squares mean difference 39.54 m [95% CI: 13.799, 65.286; p = 0.0026]). Significant and clinically meaningful improvements in 4-stair climb and 4-stair descend for deflazacort versus prednisone/prednisolone. Conclusion: Deflazacort provides clinically meaningful delays in loss of physical milestones over 48 weeks compared with prednisone/prednisolone for patients with nonsense mutation Duchenne muscular dystrophy.
KW - Duchenne muscular dystrophy
KW - deflazacort
KW - meta-analysis
KW - nonsense mutation Duchenne muscular dystrophy
KW - prednisolone
KW - prednisone
UR - http://www.scopus.com/inward/record.url?scp=85120708840&partnerID=8YFLogxK
U2 - 10.2217/cer-2021-0018
DO - 10.2217/cer-2021-0018
M3 - Article
C2 - 34693725
AN - SCOPUS:85120708840
SN - 2042-6305
VL - 10
SP - 1337
EP - 1347
JO - Journal of Comparative Effectiveness Research
JF - Journal of Comparative Effectiveness Research
IS - 18
ER -