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

• Autores: Bello, Luca; Gordish Dressman, Heather; Morgenroth, Lauren P.; Henricson, Erik K.; Duong, Tina; Hoffman, Eric P.; Cnaan, Avital; McDonald, Craig M.; Dubrovsky, Alberto; Andreone, Luz; Cooperative International Neuromuscular Research Group Investigators
• Año de publicación: 2015
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Duchenne Muscular Dystrophy; Glucocorticoid; Independent Ambulation
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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 x2 test. Results: Participants treated $1 year while ambulatory (n 5 252/340) 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 6 0.053 vs 0.490 6 0.08, p 5 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 5 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.
Fil: Bello, Luca. Children’s National Medical Center; Estados Unidos
Fil: Gordish Dressman, Heather. Children’s National Medical Center; Estados Unidos
Fil: Morgenroth, Lauren P.. Children’s National Medical Center; Estados Unidos
Fil: Henricson, Erik K.. University of California at Davis; Estados Unidos
Fil: Duong, Tina. Children’s National Medical Center; Estados Unidos
Fil: Hoffman, Eric P.. Children’s National Medical Center; Estados Unidos. The George Washington University; Estados Unidos
Fil: Cnaan, Avital. Children’s National Medical Center; Estados Unidos. The George Washington University; Estados Unidos
Fil: McDonald, Craig M.. University of California at Davis; Estados Unidos
Fil: Dubrovsky, Alberto. Cooperative International Neuromuscular Research Group; Argentina
Fil: Andreone, Luz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Cooperative International Neuromuscular Research Group; Argentina
Fil: Cooperative International Neuromuscular Research Group Investigators. No especifica;