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Research Article
19 July 2021

Steroid switching in dystrophinopathy treatment: a US chart review of patient characteristics and clinical outcomes

Authors: Jessica R Marden https://orcid.org/0000-0002-8360-7558 [email protected], Claudio Santos, Brian Pfister, Richard Able, Henry Lane, Michael Somma, Jing Zhao, James Signorovitch, Julie Parsons, and Susan ApkonAuthor Info & Affiliations
Volume 10, Number 14
https://doi.org/10.2217/cer-2021-0110
PDFFormats

Abstract

Aim: To describe reasons for switching from prednisone/prednisolone to deflazacort and associated clinical outcomes among patients with Duchenne and Becker muscular dystrophy (DMD and BMD, respectively) in the USA. Methods: A chart review of patients with DMD (n = 62) or BMD (n = 30) who switched from prednisone to deflazacort (02/2017–12/2018) collected demographic/clinical characteristics, reasons for switching, outcomes and common adverse events. Results: The mean ages at switch were 20.1 (DMD) and 9.2 (BMD) years. The primary physician-reported reasons for switching were ‘to slow disease progression’ (DMD: 83%, BMD: 79%) and ‘tolerability’ (67 and 47%). Switching was ‘very’ or ‘somewhat’ effective at addressing the primary reasons in 90–95% of patients. Conclusion: Physician-reported outcomes were consistent with deflazacort addressing patients' primary reasons for switching.

Supplementary Material

File (supplemental materials.docx)

References

Papers of special note have been highlighted as: • of interest
1.
Hoffman EP, Brown RH Jr, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51(6), 919–928 (1987).
PubMed
Google Scholar
2.
National Institute of Health (Genetic and Rare Disease Information Center). Becker muscular dystrophy. https://rarediseases.info.nih.gov/diseases/5900/becker-muscular-dystrophy
Google Scholar
3.
Romitti PA, Zhu Y, Puzhankara S et al. Prevalence of Duchenne and Becker muscular dystrophies in the United States. Pediatrics 135(3), 513–521 (2015).
PubMed
Google Scholar
4.
Darras BT, Menache-Starobinski CC, Hinton V, Kunkel LM. Chapter 30 – dystrophinopathies. In: Neuromuscular Disorders of Infancy, Childhood, and Adolescence (2nd Edition). Darras BT, Jones HR, Ryan MM, Devivo DC (Eds). Academic Press, CA, USA, 551–592 (2015).
Google Scholar
5.
Emery AEH, Muntoni F, Quinlivan R. Duchenne Muscular Dystrophy (4th Edition). Oxford University Press, UK (2015).
Google Scholar
6.
Ricotti V, Ridout DA, Scott E et al. Long-term benefits and adverse effects of intermittent versus daily glucocorticoids in boys with Duchenne muscular dystrophy. J. Neurol. Neurosurg. Psych. 84(6), 698–705 (2013).
PubMed
Google Scholar
• Assessed the use of glucocorticoids in Duchenne muscular dystrophy (DMD) in the UK and compared the benefits and risk of daily versus intermittent prednisolone regimens. Adverse effects (AEs) were more common in daily versus intermittant use, but boys with intermmitent use declined faster (per NorthStar Ambulatory Assessment) after age 7 years.
7.
Pane M, Fanelli L, Mazzone ES et al. Benefits of glucocorticoids in non-ambulant boys/men with Duchenne muscular dystrophy: a multicentric longitudinal study using the Performance of Upper Limb test. Neuromuscul. Disord. 25(10), 749–753 (2015).
PubMed
Google Scholar
• Assessed the effect of glucocorticoids on upper limb function (per performance of upper limb test) in 91 non-ambulant DMD boys and adults aged between 11 and 26 years. The 12-month changes ranged between -20 and 4 (mean -4.4), with -3.79 in the glucocorticoid group, -5.52 in those who discontinued at loss of ambulation and -4.44 in the treatment-naïve group.
8.
Mazzone E, Bianco F, Main M et al. Six minute walk test in type III spinal muscular atrophy: a 12-month longitudinal study. Neuromuscul. Disord. 23(8), 624–628 (2013).
PubMed
Google Scholar
9.
Seferian AM, Moraux A, Annoussamy M et al. Upper limb strength and function changes during a one-year follow-up in non-ambulant patients with Duchenne muscular dystrophy: an observational multicenter trial. PLoS ONE 10(2), e0113999 (2015).
PubMed
Google Scholar
10.
Passamano L, Taglia A, Palladino A et al. Improvement of survival in Duchenne muscular dystrophy: retrospective analysis of 835 patients. Acta Myol. 31(2), 121–125 (2012).
PubMed
Google Scholar
11.
Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2(12), 731–740 (2003).
PubMed
Google Scholar
12.
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).
PubMed
Google Scholar
13.
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).
PubMed
Google Scholar
• This Phase III, double-blind, randomized study assessed the safety and efficacy of deflazacort and prednisone versus placebo in 196 boys with DMD (aged 5–15 years). After 12 weeks of treatment, prednisone and both doses of deflazacort improved muscle strength versus placebo; at 52 weeks, deflazacort was associated with less weight gain than prednisone.
14.
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).
PubMed
Google Scholar
15.
Matthews DJ, James KA, Miller LA et al. Use of corticosteroids in a population-based cohort of boys with Duchenne and Becker muscular dystrophy. J. Child Neurol. 25(11), 1319–1324 (2010).
PubMed
Google Scholar
16.
United States Food and Drug Administration. Highlights of prescribing information: emflaza (deflazacort). https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208684s000,208685s000lbl.pdf
Google Scholar
17.
Center for Drug Evaluation and Research. Approval package for Emflaza (deflazacort). https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208684,208685Orig1s000Approv.pdf
Google Scholar
18.
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).
PubMed
Google Scholar
• This meta-analysis characterized disease progression among boys receiving deflazacort versus prednisone/prednisolone in two DMD clinical trials. It found that deflazacort-treated patients experienced significantly lower functional decline over 48 weeks.
19.
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).
PubMed
Google Scholar
• Assessed outcomes among 435 boys with DMD receiving deflazacort or prednisone in real-world practice. Deflazacort was also associated with a lower risk of scoliosis and better ambulatory function, greater % lean body mass, shorter stature and lower weight, after adjusting for age and steroid duration.
20.
Poysky J. Behavior patterns in Duchenne muscular dystrophy: Report on the Parent Project Muscular Dystrophy behavior workshop 8–9 of December 2006, PA, USA. Neuromuscul. Disord. 17(11), 986–994 (2007).
PubMed
Google Scholar
21.
Torgan C. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Optimizing steroid treatment for Duchenne muscular dystrophy. https://www.niams.nih.gov/newsroom/spotlight-on-research/optimizing-steroid-treatment-duchenne-muscular-dystrophy
Google Scholar
22.
Matthews E, Brassington R, Kuntzer T, Jichi F, Manzur AY. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst. Rev. 5(5), CD003725 (2016).
Google Scholar
23.
United States Food and Drug Administration. Highlights of prescribing information: rayos (prednisone). https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202020s000lbl.pdf
Google Scholar
24.
Bylo M, Farewell R, Coppenrath VA, Yogaratnam D. A review of deflazacort for patients with Duchenne muscular dystrophy. Ann. Pharmacother. 54(8), 788–794 (2020).
PubMed
Google Scholar
• Reviews the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration and other considerations of deflazacort treatment. It summarizes the evidence that deflazacort shows improved functional outcomes, delayed onset of cardiomyopathy, reduction in scoliosis surgery and improved survival.
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