Dataset Information

Deflazacort versus prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: A post HOC analysis from the ACT DMD trial.

ABSTRACT: INTRODUCTION:ACT DMD was a 48-week trial of ataluren for nonsense mutation Duchenne muscular dystrophy (nmDMD). Patients received corticosteroids for ?6 months at entry and stable regimens throughout study. This post hoc analysis compares efficacy and safety for deflazacort and prednisone/prednisolone in the placebo arm. METHODS:Patients received deflazacort (n?=?53) or prednisone/prednisolone (n?=?61). Endpoints included change from baseline in 6-minute walk distance (6MWD), timed function tests, estimated age at loss of ambulation (extrapolated from 6MWD). RESULTS:Mean changes in 6MWD were -39.0?m (deflazacort; 95% confidence limit [CL], -68.85, -9.17) and -70.6?m (prednisone/prednisolone; 95% CL, -97.16, -44.02). Mean changes in 4-stair climb were 3.79 s (deflazacort; 95% CL, 1.54, 6.03) and 6.67 s (prednisone/prednisolone; 95% CL, 4.69, 8.64). CONCLUSIONS:This analysis, limited by its post hoc nature, suggests greater preservation of 6MWD and 4-stair climb with deflazacort vs. prednisone/prednisolone. A head-to-head comparison will better define these differences. Muscle Nerve 58: 639-645, 2018.

SUBMITTER: Shieh PB

PROVIDER: S-EPMC6767037 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Deflazacort versus prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: A post HOC analysis from the ACT DMD trial.

Shieh Perry B PB Mcintosh Joseph J Jin Fengbin F Souza Marcio M Elfring Gary G Narayanan Siva S Trifillis Panayiota P Peltz Stuart W SW Mcdonald Craig M CM Darras Basil T BT

Muscle & nerve 20180927 5

<h4>Introduction</h4>ACT DMD was a 48-week trial of ataluren for nonsense mutation Duchenne muscular dystrophy (nmDMD). Patients received corticosteroids for ≥6 months at entry and stable regimens throughout study. This post hoc analysis compares efficacy and safety for deflazacort and prednisone/prednisolone in the placebo arm.<h4>Methods</h4>Patients received deflazacort (n = 53) or prednisone/prednisolone (n = 61). Endpoints included change from baseline in 6-minute walk distance (6MWD), time ...[more]

PMID: 30028519

Similar Datasets

Project description:The corticosteroid prednisone is an important component of posttransplantation immunosuppressive therapy. Pharmacokinetic parameters of prednisone or its pharmacologically active metabolite, prednisolone, are not well characterized in transplant recipients. The objective of this study was to compare the pharmacokinetics of total and unbound prednisone and prednisolone in diabetic and nondiabetic stable kidney transplant recipients and to evaluate the factors influencing plasma protein binding of prednisolone.Prednisone and prednisolone concentration-time profiles were obtained in 20 diabetic and 18 nondiabetic stable kidney transplant recipients receiving an oral dose of 5-10 mg prednisone per day. In addition to drug and metabolite exposures, factors influencing prednisolone protein binding were evaluated using a nonlinear mixed-effects modeling approach. This model takes into account the binding of prednisolone and cortisol to corticosteroid-binding globulin (CBG) in a saturable fashion and binding of prednisolone to albumin in a nonsaturable fashion. Finally, we have investigated the influence of several covariates including diabetes, glucose concentration, hemoglobin A1c, creatinine clearance, body mass index, gender, age, and time after transplantation on the affinity constant (K) between corticosteroids and their binding proteins.In patients with diabetes, the values of dose-normalized area under the concentration-time curves were 27% and 23% higher for total and unbound prednisolone, respectively. Moreover, the ratio of total prednisolone to prednisone concentrations (active/inactive forms) was higher in diabetic subjects (P < 0.001). Modeling protein binding results revealed that the affinity constant of corticosteroid-binding globulin-prednisolone (KCBG,PL) was related to the patient's gender and diabetes status.Higher prednisolone exposure could potentially lead to the increased risk of corticosteroid-related complications in diabetic kidney transplant recipients.

Dataset Information

Deflazacort versus prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: A post HOC analysis from the ACT DMD trial.

Publications

Deflazacort versus prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: A post HOC analysis from the ACT DMD trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets