Bello Luca, Gordish-Dressman Heather, Morgenroth Lauren P, Henricson Erik K, Duong Tina, Hoffman Eric P, Cnaan Avital, McDonald Craig M
From the Children's National Medical Center (L.B., H.G.-D., L.P.M., T.D., E.P.H., A.C.), Washington, DC; University of California Davis Medical Center (E.K.H., C.M.M.), Sacramento, CA; and The George Washington University (E.P.H., A.C.), Washington, DC.
Neurology. 2015 Sep 22;85(12):1048-55. doi: 10.1212/WNL.0000000000001950. Epub 2015 Aug 26.
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).
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 χ(2) test.
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.
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.
This study provides Class IV evidence that GCs are effective in delaying LoA in patients with DMD.
我们旨在对杜氏肌营养不良症（DMD）患者中独立行走能力丧失（LoA）的年龄以及与不同糖皮质激素（GC）治疗方案相关的副作用情况进行一项观察性研究。
我们研究了国际神经肌肉合作研究组杜氏自然史研究（CINRG-DNHS）中的340名参与者。LoA被定义为持续使用轮椅。通过时变Cox回归分析泼尼松或泼尼松龙（PRED）/地夫可特（DFZ）、给药频率和剂量的影响。使用χ²检验比较副作用频率。
在仍能行走时接受治疗≥1年的参与者（n = 252/340）显示LoA的中位延迟时间为3年（p < 0.001）。观察到14种不同的治疗方案。PRED非每日治疗很常见（37%），而DFZ非每日治疗很少见（3%）。与PRED相比，DFZ与更晚出现LoA相关（风险比0.294±0.053对0.490±0.08，p = 0.003；每日给药时LoA的中位差异为2年，p < 0.001）。每日PRED的平均剂量（0.56 mg/kg/d，为推荐剂量的75%）低于每日DFZ（0.75 mg/kg/d，为推荐剂量的83%，p < 0.001）。DFZ出现生长发育迟缓（p < 0.001）、库欣样外观（p = 0.002）和白内障（p < 0.001）的频率更高，但体重增加情况并非如此。
DFZ的使用与更晚出现LoA以及副作用频率增加相关。护理标准和给药方式的差异使这一发现的解读变得复杂，但在临床试验中可考虑按PRED/DFZ进行分层。本研究强调了对DMD患者的GC治疗方案进行随机、盲法试验的必要性。
本研究提供了IV级证据，表明GCs在延迟DMD患者的LoA方面是有效的。
