Variability and trends in corticosteroid use by male United States participants with Duchenne muscular dystrophy in the Duchenne Registry

Leslie Cowen, Maria Mancini, Ann Martin, Ann Lucas, Joanne M Donovan, Leslie Cowen, Maria Mancini, Ann Martin, Ann Lucas, Joanne M Donovan

Abstract

Background: Treatment options for Duchenne muscular dystrophy remain limited, although consensus treatment guidelines recommend corticosteroid use.

Methods: This retrospective analysis assessed corticosteroid use in ambulatory and nonambulatory US males with Duchenne, age 35 and under, or Becker muscular dystrophy, who enrolled in The Duchenne Registry from 2007 to 2016 (formerly DuchenneConnect).

Results: The mean (SD) age of corticosteroid use initiation was 5.9 (2.5) years, and deflazacort use (54%) was slightly more common than prednisone/prednisolone (46%). Among all responses from those with Duchenne, 63% were currently on corticosteroids, 12% were no longer on corticosteroids, and 25% had never been on corticosteroids. Among those who were nonambulatory, 49% were currently on corticosteroids, 28% had discontinued corticosteroids, and 23% had never used corticosteroids. Primary reasons for never initiating therapy were that corticosteroids were not prescribed or recommended and concerns about side effects. Corticosteroid use was maximal at age 8 (84% on corticosteroids) and gradually declined from age 10 to 19. The primary reasons for corticosteroid discontinuation were problems with side effects (65%) or not enough benefit (28%). Average doses of corticosteroids were below recommended doses. In the 159 responses with Becker muscular dystrophy, 20% were currently using corticosteroids.

Conclusions: Recognizing the self-selected nature of participation, it appears that a considerable proportion of US participants registered with The Duchenne Registry were either not on corticosteroids or not on recommended doses despite consensus recommendations. Side effects were a consideration in initiating and discontinuing treatment. These data reinforce the need for additional treatment options for those affected by Duchenne.

Keywords: Corticosteroids; Duchenne muscular dystrophy; DuchenneConnect; Rare disease registries; The Duchenne Registry.

Conflict of interest statement

Ethics approval and consent to participate

Written informed consent from participants or their parents/guardians was obtained in compliance with all local laws and regulations, and institutional investigational review board or ethics committee approval. The Duchenne Registry and electronic consent are approved by the Geisinger Institutional Review Board (Geisinger Medical Center, Danville, PA, IRB#2014–0621).

Consent for publication

Not applicable.

Competing interests

LC, MM and JD are employees of Catabasis Pharmaceuticals, the study sponsor, which is developing an investigational drug, edasalonexent, for treatment of Duchenne muscular dystrophy, which is being studied in patients not on corticosteroids.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow Diagram for Responses in The Duchenne Registry Study for Participants with Duchenne or Becker Muscular Dystrophy
Fig. 2
Fig. 2
Age Distribution at Initiation of Corticosteroid therapy for Males with Duchenne Muscular Dystrophy. Unique responses for age at corticosteroid initiation were provided by 651 males with Duchenne that had ever used steroids
Fig. 3
Fig. 3
Corticosteroid Treatment Status for Males with Duchenne Muscular Dystrophy. The percentages of males with Duchenne receiving corticosteroid therapy, no longer receiving therapy, or never on corticosteroids are shown stratified by patient age
Fig. 4
Fig. 4
Corticosteroid Status for Males with Duchenne Muscular Dystrophy Stratified by Age. Numbers of ambulatory (a) and nonambulatory (b) patients treated with corticosteroids and not treated with corticosteroids are shown by patient age
Fig. 5
Fig. 5
Average Corticosteroid Dose Stratified by Age Group for Males with Duchenne Muscular Dystrophy. Mean reported dose of prednisone or deflazacort used by males with Duchenne is shown for each age group. Horizontal lines indicate recommended prednisone (black line) and deflazacort (grey line) starting doses [19]

References

    1. Emery AE. The muscular dystrophies. Lancet. 2002;359:687–695. doi: 10.1016/S0140-6736(02)07815-7.
    1. Blake DJ, Weir A, Newey SE, Davies KE. Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev. 2002;82:291–329. doi: 10.1152/physrev.00028.2001.
    1. Ryder S, Leadley RM, Armstrong N, Westwood M, de Kock S, Butt T, et al. The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review. Orphanet J Rare Dis. 2017;12:79. doi: 10.1186/s13023-017-0631-3.
    1. Flanigan KM. Duchenne and Becker muscular dystrophies. Neurol Clin. 2014;32:671–688. doi: 10.1016/j.ncl.2014.05.002.
    1. Chen YW, Nagaraju K, Bakay M, McIntyre O, Rawat R, Shi R, et al. Early onset of inflammation and later involvement of TGFbeta in Duchenne muscular dystrophy. Neurology. 2005;65:826–834. doi: 10.1212/01.wnl.0000173836.09176.c4.
    1. McDonald CM, Mercuri E. Evidence-based care in Duchenne muscular dystrophy. Lancet Neurol. 2018;17:389–391. doi: 10.1016/S1474-4422(18)30115-7.
    1. McDonald CM, Henricson EK, Abresch RT, Duong T, Joyce NC, Hu F, 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. 2018;391:451–461. doi: 10.1016/S0140-6736(17)32160-8.
    1. Kohler M, Clarenbach CF, Bahler C, Brack T, Russi EW, Bloch KE. Disability and survival in Duchenne muscular dystrophy. J Neurol Neurosurg Psychiatry. 2009;80:320–325. doi: 10.1136/jnnp.2007.141721.
    1. Kieny P, Chollet S, Delalande P, Le Fort M, Magot A, Pereon Y, et al. Evolution of life expectancy of patients with Duchenne muscular dystrophy at AFM Yolaine de Kepper Centre between 1981 and 2011. Ann Phys Rehabil Med. 2013;56:443–454. doi: 10.1016/j.rehab.2013.06.002.
    1. Mendell JR, Goemans N, Lowes LP, Alfano LN, Berry K, Shao J, et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016;79:257–271. doi: 10.1002/ana.24555.
    1. Gloss D, Moxley RT, 3rd, Ashwal S, and 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 2016;86:465–472.
    1. Bello L, Gordish-Dressman H, Morgenroth LP, Henricson EK, Duong T, Hoffman EP, et al. Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne natural history study. Neurology. 2015;85:1048–1055. doi: 10.1212/WNL.0000000000001950.
    1. Henricson EK, Abresch RT, Cnaan A, Hu F, Duong T, Arrieta A, et al. The cooperative international neuromuscular research group Duchenne natural history study: glucocorticoid treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by manual muscle testing and other commonly used clinical trial outcome measures. Muscle Nerve. 2013;48:55–67. doi: 10.1002/mus.23808.
    1. Wong BL, Rybalsky I, Shellenbarger KC, Tian C, McMahon MA, Rutter MM, et al. Long-term outcome of interdisciplinary Management of Patients with Duchenne muscular dystrophy receiving daily glucocorticoid treatment. J Pediatr. 2017;182:296–303.e1. doi: 10.1016/j.jpeds.2016.11.078.
    1. Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010;9:77–93. doi: 10.1016/S1474-4422(09)70271-6.
    1. Ward LM, Kinnett K, Bonewald L. Proceedings of a Parent Project Muscular Dystrophy bone health workshop: morbidity due to osteoporosis in DMD: the Path forward may 12-13, 2016, Bethesda, Maryland, USA. Neuromuscul Disord. 2018;28:64–76. doi: 10.1016/j.nmd.2017.05.012.
    1. Hanaoka BY, Peterson CA, Horbinski C, Crofford LJ. Implications of glucocorticoid therapy in idiopathic inflammatory myopathies. Nat Rev Rheumatol. 2012;8:448–457. doi: 10.1038/nrrheum.2012.85.
    1. Schakman O, Gilson H, Kalista S, Thissen J. Mechanisms of muscle atrophy induced by glucocorticoids. Hormone Res. 72(Suppl 1):36–41.
    1. Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Brumbaugh D, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018;17:251–267. doi: 10.1016/S1474-4422(18)30024-3.
    1. Voelker R. First corticosteroid approved for Duchenne muscular dystrophy. Jama. 2017;317:1110.
    1. Griggs RC, Miller JP, Greenberg CR, Fehlings DL, Pestronk A, Mendell JR, et al. Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy. Neurology. 2016;87:2123–2131. doi: 10.1212/WNL.0000000000003217.
    1. Shieh PB, McIntosh J, Jin F, Souza M, Elfring G, Narayanan S, et al. Deflazacort versus prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: a post HOC analysis from the ACT DMD trial. Muscle Nerve. 2018;58:639–645. doi: 10.1002/mus.26191.
    1. Guglieri M, Bushby K, McDermott MP, Hart KA, Tawil R, Martens WB, et al. Developing standardized corticosteroid treatment for Duchenne muscular dystrophy. Contemp Clin Trials. 2017;58:34–39. doi: 10.1016/j.cct.2017.04.008.
    1. Griggs RC, Herr BE, Reha A, Elfring G, Atkinson L, Cwik V, et al. Corticosteroids in Duchenne muscular dystrophy: major variations in practice. Muscle Nerve. 2013;48:27–31. doi: 10.1002/mus.23831.
    1. Rangel V, Martin AS, Peay HL. DuchenneConnect registry report. PLoS Curr. 2012;4:RRN1309. doi: 10.1371/currents.RRN1309.
    1. Matthews E, Brassington R, Kuntzer T, Jichi F, Manzur AY. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2016:Cd003725.
    1. Kinnett K, Noritz G. The PJ Nicholoff steroid protocol for Duchenne and Becker muscular dystrophy and adrenal suppression. PLoS Curr. 2017;9. 10.1371/currents.md.d18deef7dac96ed135e0dc8739917b6e.
    1. Johnsen SD. Prednisone therapy in Becker’s muscular dystrophy. J Child Neurol. 2001;16:870–871. doi: 10.1177/08830738010160111406.
    1. Nakamura M, Sunagawa O, Hokama R, Tsuchiya H, Miyara T, Taba Y, et al. A Case of refractory heart failure in Becker muscular dystrophy improved with corticosteroid therapy. Int Heart J. 2016;57:640–644. doi: 10.1536/ihj.16-044.
    1. Biggar WD, Harris VA, Eliasoph L, Alman B. Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord. 2006;16:249–255. doi: 10.1016/j.nmd.2006.01.010.
    1. King WM, Ruttencutter R, Nagaraja HN, Matkovic V, Landoll J, Hoyle C, et al. Orthopedic outcomes of long-term daily corticosteroid treatment in Duchenne muscular dystrophy. Neurology. 2007;68:1607–1613. doi: 10.1212/01.wnl.0000260974.41514.83.
    1. Fox DJ, Kumar A, West NA, DiRienzo AG, James KA, Oleszek J. Trends with corticosteroid use in males with Duchenne muscular dystrophy born 1982-2001. J Child Neurol. 2015;30:21–26. doi: 10.1177/0883073813517263.
    1. McDonald CM, Henricson EK, Abresch RT, Han JJ, Escolar DM, Florence JM, et al. The cooperative international neuromuscular research group Duchenne natural history study--a longitudinal investigation in the era of glucocorticoid therapy: design of protocol and the methods used. Muscle Nerve. 2013;48:32–54. doi: 10.1002/mus.23807.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する