Meta-analyses of deflazacort versus prednisone/prednisolone in patients with nonsense mutation Duchenne muscular dystrophy
Publication: Journal of Comparative Effectiveness Research
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.
Supplementary Material
References
1.
Bushby K, Finkel R, Birnkrant DJ et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 9(1), 77–93 (2010).
2.
Birnkrant DJ, Bushby K, Bann CM et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 17(3), 251–267 (2018).
3.
Birnkrant DJ, Bushby K, Bann CM et al. Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan. Lancet Neurol. 17(5), 445–455 (2018).
4.
McDonald CM, Henricson EK, Abresch RT et al. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study. Lancet 391(10119), 451–461 (2018).
5.
Gloss D, Moxley RT 3rd, Ashwal S, Oskoui M. Practice guideline update summary: corticosteroid treatment of Duchenne muscular dystrophy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 86(5), 465–472 (2016).
6.
Barber BJ, Andrews JG, Lu Z et al. Oral corticosteroids and onset of cardiomyopathy in Duchenne muscular dystrophy. J. Pediatr. 163(4), 1080–1084 e1081 (2013).
7.
Desguerre I, Christov C, Mayer M et al. Clinical heterogeneity of duchenne muscular dystrophy (DMD): definition of sub-phenotypes and predictive criteria by long-term follow-up. PLoS ONE 4(2), e4347 (2009).
8.
Gopalakrishnan S, Ganeshkumar P. Systematic reviews and meta-analysis: understanding the best evidence in primary healthcare. J. Family Med. Prim. Care 2(1), 9–14 (2013).
9.
Friede T, Rover C, Wandel S, Neuenschwander B. Meta-analysis of few small studies in orphan diseases. Res. Synth. Methods 8(1), 79–91 (2017).
10.
McDonald CM, Sajeev G, Yao Z et al. Deflazacort vs prednisone treatment for Duchenne muscular dystrophy: a meta-analysis of disease progression rates in recent multicenter clinical trials. Muscle Nerve 61(1), 26–35 (2020).
11.
McDonald CM, Campbell C, Torricelli RE et al. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, Phase III trial. Lancet 390(10101), 1489–1498 (2017).
12.
Victor RG, Sweeney HL, Finkel R et al. A Phase III randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy. Neurology 89(17), 1811–1820 (2017).
13.
Bushby K, Finkel R, Wong B et al. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve 50(4), 477–487 (2014).
14.
Bonifati MD, Ruzza G, Bonometto P et al. A multicenter, double-blind, randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy. Muscle Nerve 23(9), 1344–1347 (2000).
15.
Griggs RC, Miller JP, Greenberg CR et al. Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy. Neurology 87(20), 2123–2131 (2016).
16.
Karimzadeh P, Ghazavi A. Comparison of deflazacort and prednisone in Duchenne muscular dystrophy. Iran. J. Child Neurol. 6(1), 8 (2012).
17.
Shieh PB, McIntosh J, Jin F et al. Deflazacort vs prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: a post hoc analysis from the ACT DMD trial. Muscle Nerve 58(5), 639–645 (2018).
18.
Balaban B, Matthews DJ, Clayton GH, Carry T. Corticosteroid treatment and functional improvement in Duchenne muscular dystrophy: long-term effect. Am. J. Phys. Med. Rehabil. 84(11), 843–850 (2005).
19.
Bello L, Gordish-Dressman H, Morgenroth LP et al. Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne Natural History Study. Neurology 85(12), 1048–1055 (2015).
20.
Lamb MM, West NA, Ouyang L et al. Corticosteroid treatment and growth patterns in ambulatory males with duchenne muscular dystrophy. J. Pediatr. 173, 207–213 e203 (2016).
21.
Marden JR, Freimark J, Yao Z, Signorovitch J, Tian C, Wong BL. Real-world outcomes of long-term prednisone and deflazacort use in patients with Duchenne muscular dystrophy: experience at a single, large care center. J. Comp. Eff. Res. 9(3), 177–189 (2020).
22.
Rice ML, Wong B, Horn PS, Yang MB. Cataract development associated with long-term glucocorticoid therapy in Duchenne muscular dystrophy patients. J AAPOS 22(3), 192–196 (2018).
23.
Moher D, Liberati A, Tetzlaff J, Altman DG. Prisma Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339, b2535 (2009).
24.
Muntoni F, Mercuri E, Luo G et al. Meta-analyses of ataluren in patients with nonsense mutation Duchenne muscular dystrophy. Neuromuscular Disord. 28(Suppl. 1), S12 (2018).
25.
Stanley TD, Doucouliagos H. Neither fixed nor random: weighted least squares meta-analysis. Stat. Med. 34(13), 2116–2127 (2015).
26.
McDonald CM, Henricson EK, Abresch RT et al. The 6-minute walk test and other clinical endpoints in duchenne muscular dystrophy: reliability, concurrent validity, and minimal clinically important differences from a multicenter study. Muscle Nerve 48(3), 357–368 (2013).
27.
ClinicalTrials.gov. Finding the optimum regimen for Duchenne muscular dystrophy (FOR-DMD) (2021). https://clinicaltrials.gov/ct2/show/NCT01603407
28.
Assandri A, Buniva G, Martinelli E, Perazzi A, Zerilli L. Pharmacokinetics and metabolism of deflazacort in the rat, dog, monkey and man. Adv. Exp. Med. Biol. 171, 9–23 (1984).
29.
Markham A, Bryson HM. Deflazacort. A review of its pharmacological properties and therapeutic efficacy. Drugs 50(2), 317–333 (1995).
30.
Nayak S, Acharjya B. Deflazacort versus other glucocorticoids: a comparison. Indian J. Dermatol. 53(4), 167–170 (2008).
31.
Marden JR, Santos C, Pfister B et al. Steroid switching in dystrophinopathy treatment: a US chart review of patient characteristics and clinical outcomes. J. Comp. Eff. Res. (2021) (Epub ahead of print).
32.
U.S. Food and Drug Administration. Duchenne muscular dystrophy and related dystrophinopathies: developing drugs for treatment guidance for industry (2018). www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm450229.pdf
33.
European Medicines Agency. Guideline on the clinical investigation of medicinal products for the treatment of Duchenne and Becker muscular dystrophy (2015). www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/12/WC500199239.pdf
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Pages: 1337 - 1347
PubMed: 34693725
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© 2021 Shieh et al. This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License
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Received: 22 January 2021
Accepted: 2 September 2021
Published online: 25 October 2021
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Meta-analyses of deflazacort versus prednisone/prednisolone in patients with nonsense mutation Duchenne muscular dystrophy. (2021) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2021-0018
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