Steroids in duchenne muscular dystrophy — Deflazacort trial

doi:10.1016/0960-8966(91)90099-E

Neuromuscular Disorders

Volume 1, Issue 4, 1991, Pages 261-266

https://doi.org/10.1016/0960-8966(91)90099-E Get rights and content

Abstract

We conducted a double blind controlled trial in 28 Duchenne muscular dystrophy (DMD) patients with Deflazacort (DF), an oxazoline derivative of prednisolone which reduces its side-effects. Myometric muscle strength measurements, Scott Score and timed tests showed statistically significant improvement for the treated group (P < 0.05). Side-effects after 9 months of treatment included mild cushingoid appearance in four patients (28%) and moderate in only one (7%), increased appetite in seven (50%), increased body hair in four (28%), irritability and hyperactivity in three (21%). Increased body weight was not prominent and was controlled with dietary measures. No patient had to be withdrawn from medication. More research and long-term follow-up are needed in order to establish the mechanism of improvement and the consequences of long-term steroid administration in DMD. In this regard DF appears as an alternative to prednisone preserving its benefits but with fewer side-effects.

References (19)

E.P. Hoffman et al.
Dystrophin: the protein product of the Duchenne muscular dystrophy locus
Cell
(1987)
M. Koenig et al.
Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals
Cell
(1987)
D.B. Drachman et al.
Prednisone in Duchenne muscular dystrophy
Lancet
(1974)
E.E. Zubrzycka-Gaarn et al.
The Duchenne muscular dystrophy gene product is localized in the sarcolemma of human skeletal muscle fibers
Nature
(1988)
I.M. Siegel et al.
Failure of corticosteroid in the treatment of Duchenne (pseudo hypertrophic) muscular dystrophy: report of a clinically age matched three year double-blind suty
Int Med J
(1974)
S. De Silva et al.
Prednisone treatment in Duchenne muscular dystrophy. Long term benefit
Arch Neurol
(1987)
M.H. Brooke et al.
Clinical investigation of Duchenne muscular dystrophy. Interesting results in a trial of prednisone
Arch Neurol
(1987)
J.R. Mendell et al.
Randomized double blind trial of prednisone in Duchenne's muscular dystrophy
N Eng J Med
(1989)
R.C. Griggs et al.
Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response
Arch Neurol
(1990)

There are more references available in the full text version of this article.

Cited by (98)

Treatment and Management of Muscular Dystrophies
2021, Neuromuscular Disorders: Treatment and Management
Muscular dystrophies have long been recognized as heterogeneous inherited disorders, characterized by progressive skeletal muscle degeneration, weakness, and dystrophic changes in muscle biopsy. These diseases are known to have autosomal dominant, recessive, or X-linked inheritance. The increasing understanding of genetic and biological pathology of these diseases has resulted in a tremendous increase in therapeutic approaches for many of these disorders and newly approved drugs for Duchenne muscular dystrophy, the most common childhood muscular dystrophy. A multidisciplinary approach to the diagnosis and management of muscular dystrophies remains of paramount importance.
Cataract development associated with long-term glucocorticoid therapy in Duchenne muscular dystrophy patients
2018, Journal of AAPOS
To evaluate the development of cataracts or elevated intraocular pressure (IOP) in patients with Duchenne muscular dystrophy (DMD) on long-term glucocorticoid (GC) treatment.
The medical records of DMD patients evaluated from 2010 to 2015 at a single center were reviewed retrospectively. The main outcome measures were prevalence of cataracts and elevated IOP, age of first detection of cataract, time from initial steroid use to first detection of cataract, and relative risk of cataract development for deflazacort versus prednisone treatment.
Of 596 DMD patients, 514 underwent GC therapy; all but one was male. The racial distribution was 82.1% white, 1.0% African American, 5.0% Hispanic, 2.9% Asian, and 8.0% more than one race or “other.” The prevalence of cataracts was 22.4% in patients on GC therapy. The mean age at which cataract formation was first documented was 12.9 ± 4.1 years (IQR, 9.6-14.6). The mean time from initial steroid use to the first detection of cataract was 6.5 ± 3.6 years (IQR, 4.0-8.6). The odds of cataract development were 2.4-fold higher for patients on deflazacort compared with prednisone (95% CI, 1.3-4.5; P = 0.004). Only 7 patients (1.4%) underwent cataract surgery, at a mean age of 16.9 years (range, 10.7-24.6 years); all were on deflazacort. Among patients with available intraocular pressure measurements, elevated IOP occurred in only 1 patient (1.1%), who was on deflazacort.
In patients undergoing GC therapy for DMD, the rate of cataract formation was slow and well tolerated, with a higher risk among deflazacort patients. The percentage of patients requiring cataract extraction or with elevated IOP was very small. These findings suggest that a schedule of annual eye examinations is appropriate.
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
2018, Neuromuscular Disorders
Novel Approaches to Corticosteroid Treatment in Duchenne Muscular Dystrophy
2012, Physical Medicine and Rehabilitation Clinics of North America
Idiopathic intracranial hypertension in a child with duchenne muscular dystrophy
2011, Pediatric Neurology
Citation Excerpt :
It is less potent than prednisone or prednisolone, with an estimated dose equivalency of 1.3 mg deflazacort to 1 mg prednisone [5]. Several studies reported sustained improvement in muscle strength with deflazacort administered at doses of 0.9-1.0 mg/kg/day [6,7]. In addition, deflazacort at a dose of 0.9 mg/kg/day proved as effective in preserving muscle function as prednisone at 0.75 mg/kg/day [8].
Duchenne muscular dystrophy is an X-linked, recessively inherited disorder characterized by progressive weakness attributable to the absence of dystrophin expression in muscle. In multiple studies, the chronic administration of corticosteroids slowed the loss of ambulation that develops in mid to late childhood. Corticosteroids, however, frequently produce unacceptable side effects, including Cushingoid appearance and weight gain. Deflazacort, an oxazoline analogue of prednisolone, produces equivalent benefits on muscle with fewer reported Cushingoid side effects. We present a 9-year-old boy with Duchenne muscular dystrophy who developed morbid obesity and subsequent idiopathic intracranial hypertension after 2 years of receiving deflazacort. Although deflazacort is typically thought to produce less obesity than prednisone, severe Cushingoid side effects may occur in some individuals. To our knowledge, this description is the first of idiopathic intracranial hypertension complicating chronic corticosteroid treatment of Duchenne muscular dystrophy.
Treatment and Management of Muscular Dystrophies
2011, Neuromuscular Disorders

View all citing articles on Scopus

View full text

Research paperSteroids in duchenne muscular dystrophy — Deflazacort trial

Abstract

Cell

Cell

Lancet

The Duchenne muscular dystrophy gene product is localized in the sarcolemma of human skeletal muscle fibers

Nature

Failure of corticosteroid in the treatment of Duchenne (pseudo hypertrophic) muscular dystrophy: report of a clinically age matched three year double-blind suty

Int Med J

Prednisone treatment in Duchenne muscular dystrophy. Long term benefit

Arch Neurol

Clinical investigation of Duchenne muscular dystrophy. Interesting results in a trial of prednisone

Arch Neurol

Randomized double blind trial of prednisone in Duchenne's muscular dystrophy

N Eng J Med

Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response

Arch Neurol

Research paper
Steroids in duchenne muscular dystrophy — Deflazacort trial