Mercuri Eugenio, Signorovitch James Edward, Swallow Elyse, Song Jinlin, Ward Susan J
Paediatric Neurology Unit, Catholic University, Rome, Italy.
Analysis Group, Inc., 111 Huntington Ave, 10th Floor, Boston, MA, USA; The TAP Collaboration, One Broadway, 14th Floor, Cambridge, MA, USA.
Neuromuscul Disord. 2016 Sep;26(9):576-83. doi: 10.1016/j.nmd.2016.05.016. Epub 2016 May 27.
High variability in patients' changes in 6 minute walk distance (6MWD) over time has complicated clinical trials of treatment efficacy in Duchenne muscular dystrophy (DMD). We assessed whether boys with DMD could be grouped into classes that shared similar ambulatory function trajectories as measured by 6MWD. Ambulatory boys aged 5 years or older with genetically confirmed DMD who were enrolled in a natural history study at 11 care centers throughout Italy were included. For each boy, standardized assessments of 6MWD were available at annual intervals spanning 3 years. Trajectories of 6MWD vs. age and trajectories of 6MWD vs. time from enrollment were examined using latent class analysis. A total of 96 boys were included. At enrollment, the mean age was 8.3 years (mean 6MWD: 374 meters). After accounting for age, baseline 6MWD, and steroid use, four latent trajectory classes were identified as explaining 3-year 6MWD outcomes significantly better than a single average trajectory. Patient trajectories of 6MWD change from enrollment were categorized as having fast decline (n = 25), moderate decline (n = 19), stable function (n = 37), and improving function (n = 15) during the 3-year follow-up. After accounting for trajectory classes, the standard deviation of variation in 6MWD was reduced by approximately 40%. The natural history of ambulatory function in DMD may be composed of distinct trajectory classes. The extent to which trajectories are associated with novel and established prognostic factors warrants further study. Reducing unexplained variation in patient outcomes could help to further improve DMD clinical trial design and analysis.
杜氏肌营养不良症（DMD）患者6分钟步行距离（6MWD）随时间的变化差异很大，这使得治疗效果的临床试验变得复杂。我们评估了患有DMD的男孩是否可以被分为具有相似动态功能轨迹（通过6MWD测量）的类别。纳入了年龄在5岁及以上、经基因确诊患有DMD且在意大利11个护理中心参加自然史研究的能行走的男孩。对于每个男孩，在3年的时间里每年都有6MWD的标准化评估。使用潜在类别分析检查了6MWD与年龄的轨迹以及6MWD与入组时间的轨迹。总共纳入了96名男孩。入组时，平均年龄为8.3岁（平均6MWD：374米）。在考虑年龄、基线6MWD和类固醇使用情况后，确定了四个潜在轨迹类别，它们对3年6MWD结果的解释明显优于单一的平均轨迹。在3年随访期间，患者从入组开始的6MWD变化轨迹被分类为快速下降（n = 25）、中度下降（n = 19）、功能稳定（n = 37）和功能改善（n = 15）。在考虑轨迹类别后，6MWD变化的标准差降低了约40%。DMD能行走功能的自然史可能由不同的轨迹类别组成。轨迹与新的和已确定的预后因素相关的程度值得进一步研究。减少患者结果中无法解释的变异有助于进一步改进DMD临床试验的设计和分析。
