A Review of Deflazacort for Patients With Duchenne Muscular Dystrophy

Abstract

<jats:p> Objective: The objective of this article is to review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, and formulary considerations of deflazacort. Data Sources: A search of MEDLINE and EMBASE (1946 to December 31, 2019) was conducted using the terms deflazacort and Duchenne muscular dystrophy (DMD). Results were limited to clinical trials, humans, and English. Additional sources and data were obtained from the references of included articles and prescribing information. Study Selection and Data Extraction: All articles published after July 2014 related to pharmacology, pharmacokinetics, efficacy, or safety of the therapy in human subjects were included. Data Synthesis: Deflazacort 0.9 mg/kg/d is a once-daily oral corticosteroid and is the first drug of its class to be Food and Drug Administration (FDA) approved for DMD. Studies with deflazacort show improved functional outcomes, delayed onset of cardiomyopathy, reduction in scoliosis surgery, and improved survival, but these improvements are supported by relatively weak evidence. Relevance to Patient Care and Clinical Practice: This review presents data from studies published after the most recent DMD 2016 treatment guidelines and offers prescribing considerations, including pharmacology, pharmacokinetics, adverse effects, formulary considerations, and areas of uncertainty. Conclusions: Deflazacort presents an additional, FDA-approved corticosteroid option for patients that offers improved quality of life for DMD patients. However, there is weak evidence to support these benefits; a full risk-benefit analysis considering adverse events, efficacy, cost, and previous trials of steroid therapy is necessary when selecting therapy. Further research will help clarify deflazacort’s optimal dose, duration of treatment, and impact on quality of life. </jats:p>

Cardioprotective Effect of Whole Body Periodic Acceleration in Dystrophic Phenotype mdx Rodent

“…Although various therapeutic approaches have been developed, they have not had a meaningful impact on DMD patients’ long-term health ( Schinkel et al, 2012 ; Zhang and Duan, 2012 ) or unexpectedly have aggravated the cardiomyopathy in those patients ( Townsend et al, 2009 ). Corticosteroid therapy still represents the primary treatment option, but it has serious side effects, limited skeletal muscle improvement, and it has and few to no benefits in preventing or treating DMD cardiomyopathy ( Malik et al, 2012 ; Bylo et al, 2020 ).…”

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

“…better ambulatory function compared with prednisone-treated patients [19]. A 2020 systematic literature review of the safety and efficacy of deflazacort for DMD reported that deflazacort was associated with improved functional outcomes, delayed onset of cardiomyopathy, reduction in scoliosis surgery and improved survival [24]. Thus, the trend exhibited in the present study of better CGI scores following deflazacort treatment is consistent with the prior literature which assessed specific functional changes in clinical trials and prospective databases, and contributes a new perspective specific to patients who switched from prednisone to deflazacort in a broad, representative sample of clinical practice.…”

The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene

“…Only a minority of patients can benefit from these treatments, and the mainstay of disease management is GC steroids. GC steroid treatment (mainly prednisone and Deflazacort) was shown to beneficially influence all disease trajectories, including survival and prolonged ambulation in DMD patients [ 9 – 11 ], but this benefit comes at the cost of significant side effects such as body weight (BW) increase, growth stunting, Cushing-like symptoms, mood changes, increased incidence of fractures, and susceptibility to infections [ 12 , 13 ]. Paradoxically, chronic GC steroid administration may promote muscle atrophy, and mdx mice subjected to chronic GC steroid treatment show a significant impairment of heart function and an increase of cardiac fibrosis, suggesting that prolonged steroid treatment may be detrimental to dystrophic heart muscle [ 14 , 15 ].…”