Clinical and Molecular Findings After Autologous Stem Cell Transplantation or Cyclophosphamide for Scleroderma: Handling Missing Longitudinal Data.
Clinical and Molecular Findings After Autologous Stem Cell Transplantation or Cyclophosphamide for Scleroderma: Handling Missing Longitudinal Data.
复制标题
自体干细胞移植或环磷酰胺治疗硬皮病后的临床和分子发现：处理缺失的纵向数据。
DOI：
10.1002/acr.24785
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发表时间：
2023
影响因子：
4.7
通讯作者：
Furst,Danie
中科院分区：
文献类型：
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作者：
Keyes-Elstein,Lynette;Pinckney,Ashley;Goldmuntz,Ellen;Welch,Beverly;Franks,JenniferM;Martyanov,Viktor;Wood,TammaraA;Crofford,Leslie;Mayes,Maureen;McSweeney,Peter;Nash,Richard;Georges,George;Csuka,ME;Simms,Robert;Furst,Danie
在系统性硬化症（SSc）患者中，随机分配至环磷酰胺（CYC）组（n = 34）或造血干细胞移植（HSCT）组（n = 33），我们检查了临床、肺功能和生活质量指标的纵向趋势，同时考虑了早期失败对治疗比较的影响。当比较治疗组时，使用混合效应回归模型估计临床指标的纵向趋势。将结果与观察到的平均值和共享参数模型估计的纵向趋势进行比较，假设数据不是随机缺失的。SSc内在分子子集定义的基线基因表达签名（正常样，炎症和纤维增生的签名）的纵向趋势也studyed.ResultsAvailable观察到的手段肺功能测试似乎改善随着时间的推移，在两个武器。然而，在考虑参与者损失后，HSCT接受者的用力肺活量增加了0.77个百分点/年，但CYC的用力肺活量恶化了-3.70/年（P= 0.004）。一氧化碳扩散能力和生活质量指标也有类似的结果。两种分析模型的结果是一致的。炎症（n = 20）和纤维增生（n = 20）亚组中的HSCT接受者在肺部和生活质量指标方面的长期趋势优于CYC。在纤维增生亚组中，HSCT在改良Rodnan皮肤厚度评分方面也具有上级优势。对于正常样亚组（n = 22），HSCT的优越性是不太明显。ConclusionLongitudinal趋势估计从2个统计模型肯定的疗效HSCT CYC严重SSc。未能解释早期受试者的损失可能会扭曲长期估计的临床趋势。
ObjectiveAmong individuals with systemic sclerosis (SSc) randomized to cyclophosphamide (CYC) (n = 34) or hematopoietic stem cell transplantation (HSCT) (n = 33), we examined longitudinal trends of clinical, pulmonary function, and quality of life measures while accounting for the influence of early failures on treatment comparisons.MethodsAssuming that data were missing at random, mixed‐effects regression models were used to estimate longitudinal trends for clinical measures when comparing treatment groups. Results were compared to observed means and to longitudinal trends estimated from shared parameter models, assuming that data were missing not at random. Longitudinal trends for SSc intrinsic molecular subsets defined by baseline gene expression signatures (normal‐like, inflammatory, and fibroproliferative signatures) were also studied.ResultsAvailable observed means for pulmonary function tests appeared to improve over time in both arms. However, after accounting for participant loss, forced vital capacity in HSCT recipients increased by 0.77 percentage points/year but worsened by –3.70/year for CYC (P= 0.004). Similar results were found for diffusing capacity for carbon monoxide and quality of life indicators. Results for both analytic models were consistent. HSCT recipients in the inflammatory (n = 20) and fibroproliferative (n = 20) subsets had superior long‐term trends compared to CYC for pulmonary and quality of life measures. HSCT was also superior for modified Rodnan skin thickness scores in the fibroproliferative subset. For the normal‐like subset (n = 22), superiority of HSCT was less apparent.ConclusionLongitudinal trends estimated from 2 statistical models affirm the efficacy of HSCT over CYC in severe SSc. Failure to account for early loss of participants may distort estimated clinical trends over the long term.