在巴宾纽单抗治疗轻度至中度阿尔茨海默病试验中的阿尔茨海默病评估量表-认知功能11项进展模型
Alzheimer's disease assessment scale-cognitive 11-item progression model in mild-to-moderate Alzheimer's disease trials of bapineuzumab.
作者信息
Samtani Mahesh N, Xu Steven X, Russu Alberto, Adedokun Omoniyi J, Lu Ming, Ito Kaori, Corrigan Brian, Raje Sangeeta, Brashear H Robert, Styren Scot, Hu Chuanpu
机构信息
Janssen Research & Development, LLC, NJ, USA.
Pfizer Ltd., CT, USA.
出版信息
Alzheimers Dement (N Y). 2015 Oct 9;1(3):157-169. doi: 10.1016/j.trci.2015.09.001. eCollection 2015 Nov.
INTRODUCTION
The objective of this study was to estimate longitudinal changes in disease progression (measured by Alzheimer's disease assessment scale-cognitive 11-item [ADAS-cog/11] scale) after bapineuzumab treatment and to identify covariates (demographics or baseline characteristics) contributing to the variability in disease progression rate and baseline disease status.
METHODS
A population-based disease progression model was developed using pooled placebo and bapineuzumab data from two phase-3 studies in ε4 noncarrier and carrier Alzheimer's disease (AD) patients.
RESULTS
A beta regression model with the Richard's function as the structural component best described ADAS-cog/11 disease progression for mild-to-moderate AD population. This analysis confirmed no effect of bapineuzumab exposure on ADAS-cog/11 progression rate, consistent with the lack of clinical efficacy observed in the statistical analysis of ADAS-cog/11 data in both studies. Assessment of covariates affecting baseline severity revealed that men had a 6% lower baseline ADAS-cog/11 score than women; patients who took two AD concomitant medications had a 19% higher (worse) baseline score; ε4 noncarriers had a 5% lower baseline score; and patients who had AD for a longer duration had a higher baseline score. Furthermore, shorter AD duration, younger age, ε4 carrier status, and use of two AD concomitant medications were associated with faster disease progression rates. Patients who had an ADAS-cog/11 score progression rate that was not statistically significantly different from 0 typically took no AD concomitant medications.
DISCUSSION
The beta regression model is a sensible modeling approach to characterize cognitive decline in AD patients. The influence of bapineuzumab exposure on disease progression measured by ADAS-cog/11 was not significant.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT00575055 and NCT00574132.
引言
本研究的目的是评估巴匹兹umab治疗后疾病进展的纵向变化（通过阿尔茨海默病评估量表认知11项[ADAS-cog/11]量表测量），并确定导致疾病进展率和基线疾病状态变异性的协变量（人口统计学或基线特征）。
方法
使用来自两项针对ε4非携带者和携带者阿尔茨海默病（AD）患者的3期研究的汇总安慰剂和巴匹兹umab数据，建立了基于人群的疾病进展模型。
结果
以理查德函数作为结构成分的β回归模型最能描述轻度至中度AD人群的ADAS-cog/11疾病进展。该分析证实，巴匹兹umab暴露对ADAS-cog/11进展率没有影响，这与两项研究中ADAS-cog/11数据的统计分析中观察到的临床疗效缺乏一致。对影响基线严重程度的协变量的评估显示，男性的基线ADAS-cog/11评分比女性低6%；服用两种AD伴随药物的患者基线评分高19%（更差）；ε4非携带者的基线评分低5%；AD病程较长的患者基线评分较高。此外，AD病程较短、年龄较轻、ε4携带者状态以及使用两种AD伴随药物与疾病进展速度较快相关。ADAS-cog/11评分进展率与0无统计学显著差异的患者通常未服用AD伴随药物。
讨论
β回归模型是表征AD患者认知衰退的合理建模方法。巴匹兹umab暴露对ADAS-cog/11测量的疾病进展的影响不显著。
试验注册
ClinicalTrials.gov标识符：NCT00575055和NCT00574132。
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