Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne Natural History Study

L Bello, H Gordish-Dressman, LP Morgenroth… - Neurology, 2015 - AAN Enterprises
Neurology, 2015AAN Enterprises
Objective: We aimed to perform an observational study of age at loss of independent
ambulation (LoA) and side-effect profiles associated with different glucocorticoid
corticosteroid (GC) regimens in Duchenne muscular dystrophy (DMD). Methods: We studied
340 participants in the Cooperative International Neuromuscular Research Group
Duchenne Natural History Study (CINRG-DNHS). LoA was defined as continuous
wheelchair use. Effects of prednisone or prednisolone (PRED)/deflazacort (DFZ) …
Objective
We aimed to perform an observational study of age at loss of independent ambulation (LoA) and side-effect profiles associated with different glucocorticoid corticosteroid (GC) regimens in Duchenne muscular dystrophy (DMD).
Methods
We studied 340 participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS). LoA was defined as continuous wheelchair use. Effects of prednisone or prednisolone (PRED)/deflazacort (DFZ), administration frequency, and dose were analyzed by time-varying Cox regression. Side-effect frequencies were compared using χ2 test.
Results
Participants treated ≥1 year while ambulatory (n = 252/340) showed a 3-year median delay in LoA (p < 0.001). Fourteen different regimens were observed. Nondaily treatment was common for PRED (37%) and rare for DFZ (3%). DFZ was associated with later LoA than PRED (hazard ratio 0.294 ± 0.053 vs 0.490 ± 0.08, p = 0.003; 2-year difference in median LoA with daily administration, p < 0.001). Average dose was lower for daily PRED (0.56 mg/kg/d, 75% of recommended) than daily DFZ (0.75 mg/kg/d, 83% of recommended, p < 0.001). DFZ showed higher frequencies of growth delay (p < 0.001), cushingoid appearance (p = 0.002), and cataracts (p < 0.001), but not weight gain.
Conclusions
Use of DFZ was associated with later LoA and increased frequency of side effects. Differences in standards of care and dosing complicate interpretation of this finding, but stratification by PRED/DFZ might be considered in clinical trials. This study emphasizes the necessity of a randomized, blinded trial of GC regimens in DMD.
Classification of evidence
This study provides Class IV evidence that GCs are effective in delaying LoA in patients with DMD.
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