Meunier Juliette, Creel Kristin, Loubert Angély, Larsen Klaus Groes, Aggarwal Jyoti, Hefting Nanco, Oberdhan Dorothee
Modus Outcomes, Lyon, France.
H. Lundbeck A/S, Valby, Denmark.
Front Neurol. 2024 Jul 23;15:1379062. doi: 10.3389/fneur.2024.1379062. eCollection 2024.
The Cohen-Mansfield Agitation Inventory (CMAI) quantifies the frequency of agitation behaviors in elderly persons. This analysis of data from the brexpiprazole clinical program aimed to determine a meaningful within-patient change (MWPC) threshold for CMAI Total score among patients with agitation associated with dementia due to Alzheimer's disease.
Data were included from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm trials of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease (ClinicalTrials.gov identifiers: NCT01862640, NCT01922258, NCT03548584). Change in CMAI Total score (range 29-203; higher scores indicate higher frequency of agitation behaviors) from baseline to Week 12 was the primary endpoint in each trial. MWPC thresholds were estimated from anchor-based mean change analyses and receiver operating characteristic (ROC) curves. The Clinical Global Impression-Severity of illness (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales, both as related to agitation, were used as anchors. Empirical cumulative distribution functions (eCDFs) and probability density functions (PDFs) were plotted as supportive evidence. Distribution-based methods were also employed.
Data from 898 patients were analyzed (mean age, 73.7 years; mean baseline CMAI Total score, 73.8). The mean CMAI Total score change corresponding to a difference of small improvement vs. stable (CGI-S one-point decrease vs. no change), or minimally improved vs. no change (CGI-I rating of 3 vs. 4), ranged from -10.6 to -13.5 points. The mean CMAI Total score change corresponding to a difference of moderate improvement vs. stable (CGI-S two-point decrease vs. no change), or much improved vs. no change (CGI-I rating of 2 vs. 4), ranged from -20.2 to -25.7 points. ROC curve analyses generally produced smaller estimates of meaningful change. eCDFs and PDFs showed good distribution and separation of CMAI Total score change between CGI-S/CGI-I categories. In distribution-based analyses, the minimal detectable change for CMAI Total score (10.5-11.8 points) was generally lower than anchor-suggested thresholds.
Triangulation of evidence from anchor- and distribution-based analyses supports an MWPC threshold for CMAI Total score of -20 points, with a threshold range of -15 to -25 points, in patients with agitation associated with dementia due to Alzheimer's disease.
科恩-曼斯菲尔德激越量表（CMAI）用于量化老年人激越行为的频率。本对布雷哌唑临床项目数据的分析旨在确定阿尔茨海默病所致痴呆伴激越患者中CMAI总分有意义的患者内变化（MWPC）阈值。
数据来自三项为期12周、多中心、随机、双盲、安慰剂对照、平行组的布雷哌唑治疗阿尔茨海默病所致痴呆伴激越的试验（ClinicalTrials.gov标识符：NCT01862640、NCT01922258、NCT03548584）。每项试验的主要终点是从基线到第12周CMAI总分的变化（范围为29 - 203；分数越高表明激越行为频率越高）。MWPC阈值通过基于锚定的平均变化分析和受试者工作特征（ROC）曲线进行估计。使用与激越相关的临床总体印象-疾病严重程度（CGI-S）和临床总体印象-改善（CGI-I）量表作为锚定指标。绘制经验累积分布函数（eCDF）和概率密度函数（PDF）作为支持证据。还采用了基于分布的方法。
分析了898例患者的数据（平均年龄73.7岁；平均基线CMAI总分73.8）。对应于小改善与稳定（CGI-S降低1分与无变化）或最小改善与无变化（CGI-I评分为3与4）差异的CMAI总分平均变化范围为 - 10.6至 - 13.5分。对应于中度改善与稳定（CGI-S降低2分与无变化）或明显改善与无变化（CGI-I评分为2与4）差异的CMAI总分平均变化范围为 - 20.2至 - 25.7分。ROC曲线分析通常得出较小的有意义变化估计值。eCDF和PDF显示了CMAI总分变化在CGI-S/CGI-I类别之间的良好分布和区分。在基于分布的分析中，CMAI总分的最小可检测变化（10.5 - 11.8分）通常低于锚定指标建议的阈值。
基于锚定和分布分析的证据三角支持在阿尔茨海默病所致痴呆伴激越患者中，CMAI总分的MWPC阈值为 - 20分，阈值范围为 - 15至 - 25分。
