More of what matters, year after year^10,11

3 Key Milestones.
A 10-Year
Follow-up Study.¹⁰

Deflazacort demonstrated differences
vs prednisone over time¹⁰

A prospective natural history observational cohort study with 440 patients ages 2 to 28 years, which evaluated the long-term effects of corticosteroids in DMD. Patients were followed up for 10 years. Patients were stratified by duration of corticosteroid treatment (<1 month or ≥12 months). Milestones for 9 groups of the Davis Duchenne Functional assessments were recorded and analyzed using Kaplan-Meier to measure disease progression.¹⁰

McDonald 2018 Study Summary

Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study

A prospective natural history observational cohort study with 440 patients ages 2 to 28 years, which evaluated the long-term effects of glucocorticoids in DMD. Patients were followed up for 10 years. Patients were stratified by duration of glucocorticoid treatment (<1 month or ≥12 months). Milestones for 9 groups of the Davis Duchenne Functional assessments were recorded and analyzed using Kaplan-Meier to measure disease progression.

The study also compared patients treated with prednisone or prednisolone (PRED) versus those treated with deflazacort (DFZ) for age at loss of milestones. Patients with cumulative glucocorticoid treatment duration of 1 year or longer had consistently delayed occurrence of ambulatory disease progression milestones by periods of 2.1 to 4.4 years compared with glucocorticoid-naive patients or those treated for less than 1 month (all log-rank, apart from time to climb four stairs). Glucocorticoid treatment for 1 year or longer was associated with significantly delayed loss of upper limb milestones by 2.8 to 8.0 years compared with treatment for less than 1 month. DFZ was associated with increased median age at loss of three milestones (age at: loss of ability to stand from supine, loss of ambulation, loss of hand-to-mouth function with retained hand function) by 2.1 to 2.7 years in comparison with PRED (log-rank). The mean age at loss of the earliest milestones typically reached (ie, supine to stand ≥5 seconds and supine to stand ≥10 seconds) showed trends in delayed loss of function favoring deflazacort, but differences between agents were not significant. Insufficient numbers of milestone transitions were observed to allow a comparison between glucocorticoid regimens for loss of distal hand function. The most common side effects of glucocorticoid treatment were weight gain, Cushingoid features, behavior changes, growth delay, fractures, cataracts, and skin changes.

Study Limitations

Based upon the study design and enrollment, the following limitations should be considered:

Steroid use was not randomized as might be in a controlled clinical trial
Comparisons between DFZ and PRED are not included in the approved Prescribing Information for DFZ, as PRED is not an approved treatment for DMD
The analyses included a comparison of multiple glucocorticoid agents and regimens (such as daily vs intermittent dosing)
An in-depth analysis of specific doses or schedules was not feasible in a long-term, prospective, observational, natural history study
DFZ and PRED utilized in this study were from various manufacturers in and outside the United States
Potential differences were noted in socioeconomic status of patients and caregivers—DFZ was not commercially available in the United States at the time of the study
DFZ may have been used more frequently in a daily dosing regimen
The daily doses of DFZ used in the population were closer to that of the benchmarked FDA-approved labeled dose of 0.90 mg/kg/day

Financial Disclosures of Study Sponsors

This study was supported by US Department of Education/NIDRR (#H133B031118, #H133B090001); US Department of Defense (#W81XWH-12-1-0417); National Institutes of Health/NIAMS (#R01AR061875); and Parent Project Muscular Dystrophy.
McDonald CM, Henricson EK, Abresch RT, et al; CINRG Investigators. 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(10119):451-461.

Deflazacort can help maintain muscle function, which may prolong ambulation¹⁰

Acting with A mind toward lung function²

Not an actual patient.

Deflazacort Preserved Pulmonary Function Better Than Prednisone²

Results from a real-world, single-center, retrospective cohort analysis of 435 boys with DMD who attended the Comprehensive Neuromuscular Center at Cincinnati Children’s Hospital Medical Center (CCHMC) from 2004 to March 2017.²

Marden 2020 Study Summary

Real-world outcomes of long-term prednisone and deflazacort use in patients with Duchenne muscular dystrophy: experience at a single, large care center

A retrospective study assessing outcomes among patients with DMD receiving deflazacort or prednisone in real-world practice. 435 DMD patients, aged 4 years and older, who attended the CCHMC from 2004 to March 2017 were studied retrospectively using time-to-event and regression analyses. Loss of ambulation was identified as functional mobility scale (FMS) score >4, which is indicative of patients’ full-time use of a wheelchair for mobility in DMD. Age at onset of scoliosis was defined as the first recorded clinical diagnosis of scoliosis in the patient’s medical record. Age at first occurrence of FMS >4 and first diagnosis of scoliosis were studied in time-to-event analyses, with age as the time variable, and censoring at the end of data availability. Kaplan-Meier curves and log-rank tests were calculated to compare these outcomes between steroid initiation groups. Cox proportional hazards analyses were used to estimate the association between steroid type and age at event while adjusting for age at steroid initiation, the calendar year during which the patient had initiated steroid use, and whether the patient had initiated steroids prior to or after their first clinic visit at CCHMC. The adjusted analyses thus accounted for differences in the duration of steroid exposure, potential temporal trends that might impact outcomes across groups, and potential differences in care received prior to CCHMC. Sensitivity analyses were conducted distinguishing between patients who received daily versus other regimens of prednisone and, separately, distinguishing those who maintained prednisone versus those who switched to deflazacort after initiation.
Among n = 600 total boys in the CCHMC database, n = 559 had their date of steroid initiation recorded and n = 500 had a steroid type recorded at some point during their follow-up history at CCHMC. A further n = 435 of these patients had at least one assessment of FMS or an assessment for scoliosis. The overall average follow-up included in the time-to-event analyses was 11.2 years in the FMS analyses and 11.9 years in the scoliosis analyses. The follow-up time was similar across prednisone- and deflazacort-initiated patients (<6 months difference in mean follow-up time). At first clinic visit at CCHMC with functional data recorded, deflazacort-initiated patients were on average younger, shorter and weighed less, compared with prednisone-initiated patients. The deflazacort-initiated group was also younger on average at steroid initiation compared with the prednisone-initiated group (5.7 vs 6.4 years, respectively). Across measures of ambulatory, pulmonary and cardiac function at the first clinic visit at CCHMC, deflazacort-treated patients tended to have better or similar function compared with prednisone-treated patients.

Study Limitations

Steroid use was not randomized as in a clinical trial. Therefore:

Differences in outcomes between steroid groups could be confounded by factors that differ between these groups
It could also be hypothesized that differences in care received prior to CCHMC, including potential differences in steroid dosing or supportive care, could have impacted outcomes
A higher proportion of patients initiating prednisone did so prior to CCHMC compared with those initiating deflazacort it is possible that unobserved differences are present
Cost has been a factor for most families at CCHMC who opt for prednisone instead of out-of-pocket, imported deflazacort
The impact of different dosing regimens is a plausible contributor to the differences in outcomes observed in the present study between patients receiving prednisone and deflazacort
Ambulatory test results were not available from patients who were unable or unwilling to complete the assessments

This study was facilitated by cTAP with funding from PTC. cTAP is a pre-competitive coalition of academic clinicians, drug developers and patient foundations formed in 2015 to overcome challenges affecting clinical trials in DMD. cTAP has received sponsorship from Astellas Pharma (Mitobridge), BioMarin, Biophytis, Bristol-Myers Squibb, Catabasis, FibroGen, Inc., Italfarmaco SpA, Marathon Pharmaceuticals, Pfizer, Inc., PTC Therapeutics, Roche, Sarepta Therapeutics, Shire plc, Solid Biosciences, Summit Plc., Wave Life Sciences, Parent Project Muscular Dystrophy, Charley’s Fund and CureDuchenne, a founding patient advocacy partner and provider of initial seed funding to cTAP.

Marden JR, Freimark J, Yao Z, Signorovitch J, Tian C, Wong BL. Real-world outcomes of long-term prednisone and deflazacort use in patients with Duchenne muscular dystrophy: experience at a single, large care center. J Comp Eff Res. 2020;9(3):177-189.

Study Limitations

Comparisons between deflazacort and prednisone are not included in the Prescribing Information for deflazacort because prednisone is not an approved treatment for DMD.