Comparing Deflazacort and Prednisone in Duchenne Muscular Dystrophy.

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. 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.

Development of a New Self-Reporting Instrument Measuring Benefits and Side Effects of Corticosteroids in Duchenne Muscular Dystrophy: Report from a Pilot Study.

BACKGROUND: There is no cure for Duchenne Muscular Dystrophy (DMD); treatment is symptomatic and corticosteroids slow the progression. Side effects of corticosteroids - especially the physical effects - have been described, however patients' and caregivers perception on chronic corticosteroid treatment and their side effects is less well known, in particular with regards to cognition, behaviour, and emotional functioning. OBJECTIVE: The primary aim of this pilot study was to (i) construct a self-report questionnaire to assess the perceived benefits and side effects of corticosteroids for patients with DMD and their parents. Furthermore we aimed to (ii) investigate the psychometric qualities of this questionnaire, (iii) whether there was a difference between parents' and patient's perceptions, and finally (iv) to what extent reported side effects may alter over time. METHODS: A 23-item questionnaire (SIDECORT: side effect of corticosteroids) was constructed to assess the perception of these benefits and side effects in a systematic manner. RESULTS: In total, 86 patients (aged 5 - 28 years) and 125 of their parents completed the questionnaire. Internal consistency was good. Using factor analyses on the side effect items as reported by parents, two underlying factors were found, with the first factor describing cognitive, behavioural and emotional functioning, and the second factor describing physical functioning. The potential benefits of corticosteroids were highly rated among both parents and patients, although parents rated the importance of the benefits higher than their sons (p = 0.002). Similarly, parents rated the severity of the side effects generally higher than their sons (p = 0.011), especially with regards to the physical side effects (p = 0.014). Based on the parent's perception, the neurodevelopmental side effects generally appeared to decline the longer corticosteroids were used. CONCLUSIONS: To our knowledge, this is the first explicit study on perceived cognitive-, behavioural-, and emotional side effects and the allocation of benefits to corticosteroids in DMD. On the basis of our research we suggest a short form questionnaire, which proves to be reliable and valid for research- and clinical practice. This questionnaire could provide useful insights for the care of boys and men with DMD.

Glucocorticoid treatment for the prevention of scoliosis in children with Duchenne muscular dystrophy: long-term follow-up.

BACKGROUND: Duchenne muscular dystrophy, a progressive muscle disorder that occurs in males, causes a gradual decline in muscle strength. This progressive decline is associated with the development of scoliosis. Previous studies have shown that the use of glucocorticoids slows the progression of scoliosis, but it is unknown if the spine remains straight in the long term. We examined if glucocorticoid treatment has a long-term effect on the prevalence of scoliosis. METHODS: Fifty-four boys who had been diagnosed with Duchenne muscular dystrophy while they were still walking were enrolled in a non-randomized comparative study of the glucocorticoid deflazacort. The families of thirty boys elected for them to use glucocorticoid treatment and the families of twenty-four boys elected for them not to have this treatment. The boys were matched for important baseline characteristics including age and pulmonary function. Every four to six months, they were examined for the development of scoliosis, and the duration of follow-up for surviving patients was fifteen years. Because surgery was recommended for spinal curves measuring >20° on sitting posteroanterior radiographs, a curve of this magnitude was used as the definition for a patient developing scoliosis. RESULTS: Five boys (21%) in the non-treatment group and one boy (3%) in the glucocorticoid treatment group died. At the most recent follow-up, of the boys who survived, six (20%) in the glucocorticoid treatment group and twenty-two (92%) in the non-treatment group developed scoliosis and underwent spinal surgery. After fifteen years of follow-up, the survivorship analysis (avoiding surgery) was 78% (95% confidence interval, 57% to 89%) in the treatment group and 8.3% (95% confidence interval, 0.8% to 28%) in the non-treatment group. Significance (p = 5.8 × 10(-7)) was calculated with log-rank and chi-square tests. None of the patients in the glucocorticoid group developed scoliosis after ten years of deflazacort treatment. CONCLUSION: The long-term use of the glucocorticoid results in a substantial decreased need for spinal surgery to treat scoliosis.

The Canadian experience with long-term deflazacort treatment in Duchenne muscular dystrophy.

Deflazacort is the most commonly prescribed corticosteroid for the treatment of Duchenne muscular dystrophy in Canada. We review the long-term experience with deflazacort treatment at two centers in Canada; Montreal and Toronto. Deflazacort has benefitted both cohorts by prolonged ambulation, preserved cardiac and respiratory function, less scoliosis and improved survival. Common side effects in both cohorts include weight gain, decreased height and cataract formation. The Canadian experience supports the use of deflazacort in treating boys with Duchenne muscular dystrophy.

Alendronate in the treatment of low bone mass in steroid-treated boys with Duchennes muscular dystrophy.

OBJECTIVE: To examine alendronates side-effect profile and effect on bone mineral density (BMD) in deflazacort-treated boys with Duchennes muscular dystrophy (DMD) and low BMD. DESIGN: Before-after trial. SETTING: Neuromuscular clinic at a children's hospital in Canada between 1999 and 2000. PARTICIPANTS: All consenting boys with DMD who had z scores less than -1.00 (spine and/or total body) and in whom BMD testing was feasible. INTERVENTION: Boys received .08 mg.kg(-1) .d(-1) of alendronate orally, with 750 mg of daily calcium and 1000 IU of vitamin D. BMD, height, weight, physical activity, Tanner stage, and adverse effects were followed for 2 years. MAIN OUTCOME MEASURES: BMD z scores at the lumbar spine (L1-4) and total body. RESULTS: Of the 42 eligible boys assessed, 23 had low BMD; for 16 of the 23, future BMD testing was feasible. Mean age was 10.8 years (range, 6.9-15.6 y). Mean baseline z scores at the total body and spine were -0.80 and -1.94, respectively. At 2 years, mean z scores were unchanged. Furthermore, alendronate response varied by baseline age. In multivariable analysis, improvement in total body and spine z scores was associated with younger age at baseline ( P =.01 for both). CONCLUSIONS: In deflazacort-treated boys, alendronate had a positive effect on BMD z scores; the effect was greatest when given early in the course of disease.

Steroid treatment and the development of scoliosis in males with duchenne muscular dystrophy.

BACKGROUND: Scoliosis due to progressive muscle weakness occurs in almost all males with Duchenne muscular dystrophy, and it progresses relentlessly. Previous studies have shown that corticosteroid treatment slows the decline in muscle strength and stabilizes muscle strength in patients with this disease. We hypothesized that steroids may also attenuate the development of scoliosis. The purpose of this study was to compare the prevalence of scoliosis in male patients with Duchenne muscular dystrophy who received steroids with a control group of such patients who did not. METHODS: A group of seven to ten-year-old boys with Duchenne muscular dystrophy who were able to walk were enrolled in a nonrandomized comparative study to determine the effect of deflazacort (a derivative of prednisone) on muscle strength and pulmonary function. Thirty patients were treated with deflazacort (treatment group), and twenty-four were not (control group). The patients were matched for age and pulmonary function at baseline. To assess the development of scoliosis, the patients in each group were followed for at least five years. Survival curves were plotted to determine the chance of scoliosis of >/==" BORDER="0">20 degrees developing. The difference between the groups with respect to the chance of scoliosis developing was determined with Kaplan-Meier analysis. RESULTS: A curve of >/==" BORDER="0">20 degrees developed during the follow-up period in sixteen (67%) of the twenty-four patients in the control group but in only five (17%) of the thirty patients in the treatment group. Fifteen of the twenty-four patients in the control group underwent spine surgery, at a mean age of thirteen years, whereas only five of the thirty patients in the treatment group underwent spine surgery, at a mean age of fifteen years. Kaplan-Meier analysis demonstrated a significant difference between the two groups with regard to development of scoliosis of >/==" BORDER="0">20 degrees (p < 0.001). Cataracts developed in ten patients in the treatment group, and stress fractures developed in three patients in the treatment group. Patients in the treatment group weighed a mean of 3.7 kg more than did those in the control group. CONCLUSIONS: Steroid treatment slows the progression of scoliosis in males with Duchenne muscular dystrophy; however, longer-term evaluation will be necessary to determine if the treatment prevents the development of scoliosis or just delays its onset. At the very least, steroid treatment delays the need for spinal surgery. LEVEL OF EVIDENCE: Therapeutic study, Level II-1 (prospective cohort study). See Instructions to Authors for a complete description of levels of evidence.

Duchenne muscular dystrophy: current knowledge, treatment, and future prospects.

The cloning of the dystrophin gene has led to major advances in the understanding of the molecular genetic basis of Duchenne, Becker, and other muscular dystrophies associated with mutations in genes encoding members of the dystrophin-associated glycoprotein complex. The recent introduction of pharmaceutical agents such as prednisone has shown great promise in delaying the progression of Duchenne muscular dystrophy but there remains a need to develop more long-term therapeutic interventions. Knowledge of the nature of the dystrophin gene and the glycoprotein complex has led many researchers to think that somatic gene replacement represents the most promising approach to treatment. The potential use of this strategy has been shown in the mdx mouse model of Duchenne muscular dystrophy, where germ line gene transfer of either a full-length or a smaller Becker-type dystrophin minigene prevents necrosis and restores normal muscle function.