Pfizer Inc, Cambridge, MA, USA.
Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Sci Rep. 2022 Nov 5;12(1):18762. doi: 10.1038/s41598-022-23072-5.
We evaluated whether whole-body dual-energy X-ray absorptiometry (DXA) measures of lean body mass can be used as biomarkers for disease progression and treatment effects in patients with Duchenne muscular dystrophy. This post hoc analysis utilized data from a randomized, 2-period study of domagrozumab versus placebo in 120 ambulatory boys with DMD. DXA measures of lean body mass were obtained from the whole body (excluding head), arms, legs and appendicular skeleton at baseline and every 16 weeks. Treatment effects on DXA measures for domagrozumab versus placebo were assessed at Week 49. At Week 49, domagrozumab statistically significantly increased lean body mass versus placebo in the appendicular skeleton (p = 0.050) and arms (p < 0.001). The relationship between lean body mass at Week 49 and functional endpoints at Week 97 was evaluated. Changes in lean body mass at Week 49 in all regions except arms were significantly correlated with percent change from baseline in 4-stair climb (4SC) at Week 97. DXA-derived percent lean mass at Week 49 also correlated with 4SC and North Star Ambulatory Assessment at Week 97. These data indicate that whole-body DXA measures can be used as biomarkers for treatment effects and disease progression in patients with DMD, and warrant further investigation.Trial registration: ClinicalTrials.gov, NCT02310763; registered 8 December 2014.
我们评估了全身双能 X 射线吸收法 (DXA) 测量的瘦体重是否可以作为杜氏肌营养不良症 (DMD) 患者疾病进展和治疗效果的生物标志物。这项事后分析利用了一项多格列单抗与安慰剂在 120 名可走动的 DMD 男孩中进行的随机、2 期研究的数据。基线和每 16 周从全身（不包括头部）、手臂、腿部和四肢骨骼获得 DXA 瘦体重测量值。在第 49 周评估多格列单抗与安慰剂对 DXA 测量值的治疗效果。在第 49 周，与安慰剂相比，多格列单抗在四肢骨骼（p=0.050）和手臂（p<0.001）上的瘦体重有统计学显著增加。评估第 49 周的瘦体重与第 97 周的功能终点之间的关系。第 49 周除手臂外所有区域的瘦体重变化与第 97 周 4 级爬梯（4SC）从基线的百分比变化显著相关。第 49 周的 DXA 衍生的瘦体重百分比也与 4SC 和 North Star 可移动评估在第 97 周相关。这些数据表明，全身 DXA 测量值可作为 DMD 患者治疗效果和疾病进展的生物标志物，值得进一步研究。试验注册：ClinicalTrials.gov，NCT02310763；2014 年 12 月 8 日注册。
