Comparing Deflazacort and Prednisone in Duchenne Muscular Dystrophy

Abstract

Abstract. Deflazacort and prednisone/prednisolone are the current standard of care for patients with Duchenne muscular dystrophy (DMD) based on evidence that they improve muscle strength, improve timed motor function, delay loss of ambulation, improve pulmonary function, reduce the need for scoliosis surgery, delay onset of cardiomyopathy, and increase survival. Both have been used off-label for many years (choice dependent on patient preference, cost, and geographic location) before FDA approval of deflazacort for DMD in 2017. In this review, we compare deflazacort and prednisone/prednisolone in terms of their key pharmacological features, relative efficacy, and safety profiles in patients with DMD. Differentiating features include lipid solubility, pharmacokinetics, changes in gene expression profiles, affinity for the mineralocorticoid receptor, and impact on glucose metabolism. Evidence from randomized clinical trials, prospective studies, meta-analyses, and post-hoc analyses suggests that patients receiving deflazacort experience similar or slower rates of functional decline compared with those receiving prednisone/prednisolone, with the strongest evidence being for improved muscle strength with deflazacort. Regarding side effects, weight gain and behavior side effects appear to be greater with prednisone/prednisolone than with deflazacort, whereas bone health, growth parameters, and cataracts appear worse with deflazacort.

Functional and Clinical Outcomes Associated with Steroid Treatment among Non-ambulatory Patients with Duchenne Muscular Dystrophy

“…A greater share of deflazacort- than prednisone-treated patients were on daily regimens (95.0% vs. 41.4%) and received a higher mean dose (0.61 [SD: 0.22] vs. 0.39 [0.20] mg/kg). Among the subgroup of patients on daily steroids ( n = 50), the average daily dose remained higher for deflazacort (0.61 [SD: 0.22] mg/kg/day, equivalent to 68.2% [ 24.8% ] of the recommended daily dose; n = 38) relative to prednisone (0.27 [0.16] mg/kg/day, equivalent to 36.4% [ 21.0% ] of the recommended daily dose; n = 12) (data not shown). Patients were followed for an average of 21.4 months after index, with deflazacort patients followed for a slightly shorter time relative to others (17.4 vs. 25.9 [prednisone] and 23.1 months [no steroids]) (data not shown).…”

“…The AAN guidelines classify a greater share of prednisone's efficacy evidence as Level B ("probably" effective) than Level C ("possibly" effective) [11] compared to deflazacort, but a 2016 Cochrane Review considered the quality of comparative evidence to be low [20]. More recent studies have suggested that relative to patients treated with prednisone, patients treated with deflazacort experience similar or slower rates of functional decline and different side effects [21]. A meta-analysis of placebo arm data from phase III trials found that functional decline over 48 weeks was significantly slower for deflazacort versus prednisone for five measures of ambulatory function and comparable for a sixth measure [18].…”

Targeting gut dysbiosis against inflammation and impaired autophagy in Duchenne muscular dystrophy

“…However, there is uncertainty regarding the long‐term benefits and safety of these treatments. Results from randomized controlled studies revealed that side effects including sudden weight gain, confusion, depression, growth‐related complication, and cataracts may be caused by both DFZ and PRED (Matthews et al , 2016; Biggar et al , 2022).…”

Functional abilities, respiratory and cardiac function in a large cohort of adults with Duchenne muscular dystrophy treated with glucocorticoids

“…Individuals were assessed every 6-12 months by clinicians and physiotherapists specialized in neuromuscular diseases. Clinical notes were reviewed to collect demographic, genetic, treatment [4,5,[22][23][24], functional abilities (Egen Klassifikation [EK] scale version 2) [25][26][27], respiratory and cardiac data [28]. The inclusion criteria were (i) males genetically diagnosed with DMD ≥16 years old at last assessment (LA) and (ii) ambulant or nonambulant at LA.…”