Lilly Research Laboratories, Indianapolis, IN, USA.
Lilly Research Laboratories, Indianapolis, IN, USA.
Alzheimers Dement. 2015 Jan;11(1):24-31. doi: 10.1016/j.jalz.2013.11.008. Epub 2014 Mar 6.
Interpreting Alzheimer's disease (AD) clinical trial (CT) outcomes is complicated by treatment dropouts and adverse events (AEs). In elderly participants, AE rates, dropouts, and deaths are important considerations as they may undermine the validity of clinical trials. Published discontinuation and safety data are limited.
Safety data from 1054 placebo-treated participants in IDENTITY and IDENTITY-2, 76-week, Phase 3 AD studies conducted in 31 countries, were pooled, annualized, and summarized overall, by country and age group.
Median age was 74.2 (interquartile range 67.9-79.5) years; 57.4% were female; and median observation time was 63.2 (interquartile range 41.6-77.4) weeks when study drug dosing was halted. Overall annualized rates for discontinuations, discontinuations due to AEs, serious adverse events (SAEs), and deaths were 21.6% (range 19.6%-24.0%), 8.2% (range 8.1%-8.3%), 12.0%, and 1.7%, respectively. AE and discontinuation rates varied by country and age groups. Fall, pneumonia, and atrial fibrillation AEs were more frequent in the oldest age group.
These annualized placebo safety data provide insight into the course of enrolled patients with mild-to-moderate AD, and are useful in planning longer term trials and in monitoring safety.
解释阿尔茨海默病（AD）临床试验（CT）结果较为复杂，因为存在治疗脱落和不良事件（AE）。在老年参与者中，AE 发生率、脱落率和死亡率是重要的考虑因素，因为它们可能影响临床试验的有效性。已发表的停药和安全性数据有限。
对在 31 个国家开展的为期 76 周的 IDENTITY 和 IDENTITY-2 两项 3 期 AD 研究中 1054 例接受安慰剂治疗的参与者的安全性数据进行汇总分析，评估总体、各国和各年龄组的年化停药率和安全性。
中位年龄为 74.2 岁（四分位距 67.9-79.5）；57.4%为女性；当停止研究药物剂量时，中位观察时间为 63.2 周（四分位距 41.6-77.4）。总年化停药率、因 AE 停药率、严重不良事件（SAE）停药率和死亡率分别为 21.6%（范围 19.6%-24.0%）、8.2%（范围 8.1%-8.3%）、12.0%和 1.7%。AE 和停药率因国家和年龄组而异。在年龄最大的组中，跌倒、肺炎和心房颤动 AE 更为常见。
这些年化安慰剂安全性数据为评估轻度至中度 AD 患者的入组患者病程提供了参考，并有助于规划更长期的临床试验和监测安全性。
