Placebo Rates in Crohn's Disease Randomized Clinical Trials: An Individual Patient Data Meta-Analysis.

We assessed placebo rates and associated factors using individual patient data from Crohn's disease trials.

我们使用克罗恩病试验的个体患者数据评估了安慰剂反应率及其相关因素。

Methods

We conducted a meta-analysisof phase 2/3 placebo-controlledtrials evaluating advanced therapies in moderate to severe Crohn's disease (2010-2021).

我们对2010-2021年间评估中度至重度克罗恩病先进疗法的2/3期安慰剂对照试验进行了荟萃分析。

Deidentified individual patient data were obtained through Vivli Inc and the Yale University Open Data Access Project.

通过Vivli Inc和耶鲁大学开放数据访问项目获得了去标识化的个别患者数据。

Primary outcomes were clinical response and remission.

主要结果是临床反应和缓解。

Pooled placebo rates and 95% confidence intervals (CIs) were estimated using 1- and 2-stage meta-analytic approaches.

使用1阶段和2阶段的荟萃分析方法估计了合并安慰剂率和95%置信区间（CIs）。

Regression analyses identified patient-level factors associated with placebo rates.

回归分析确定了与安慰剂反应率相关的患者层面因素。

Results

Analysis of individual patient data from 8 induction (n = 1147) and 4 maintenance (n = 524) trials showed overall placebo clinical response and remission rates for induction were 27% (95% CI, 23%-32%) and 10% (95% CI, 8%-14%), respectively, and 32% (95% CI, 23%-42%) and 22% (95% CI, 14%-33%) for maintenance, respectively.

对来自8个诱导期（n=1147）和4个维持期（n=524）试验的个别患者数据进行分析显示，诱导期的总体安慰剂临床反应和缓解率分别为27%（95%置信区间，23%-32%）和10%（95%置信区间，8%-14%），维持期则分别为32%（95%置信区间，23%-42%）和22%（95%置信区间，14%-33%）。

Among biologic (bio)-naïve patients, placebo response and remission rates during induction were 29% (95% CI, 24%-35%) and 11% (95% CI, 8%-15%) respectively, and 26% (95% CI, 20%-33%) and 10% (95% CI, 8%-14%) for biologic (bio)-exposed patients, respectively.

在生物制剂（bio）未经治疗的患者中，诱导期间安慰剂反应和缓解率分别为29%（95%置信区间，24%-35%）和11%（95%置信区间，8%-15%），而在生物制剂暴露过的患者中，相应的反应和缓解率分别为26%（95%置信区间，20%-33%）和10%（95%置信区间，8%-14%）。

During maintenance, biologic-naïve response and remission rates were 41% (95% CI, 34%-48%) and 32% (95% CI, 24%-40%), respectively, and 29% (95% CI, 24%-34%) and 16% (95% CI, 13%-21%) for bio-exposed, respectively.

在维持治疗期间，生物制剂未经治疗患者的反应和缓解率分别为41%（95%置信区间，34%-48%）和32%（95%置信区间，24%-40%），而在生物制剂暴露过的患者中，相应的反应和缓解率分别为29%（95%置信区间，24%-34%）和16%（95%置信区间，13%-21%）。

Higher baseline C-reactive protein concentration predicted lower placebo rates, whereas higher baseline albumin levels and body mass index increased the odds of placebo outcomes.

较高的基线C反应蛋白浓度预测了较低的安慰剂反应率，而较高的基线白蛋白水平和体重指数增加了安慰剂结果的几率。

Increased baseline Crohn's Disease Activity Index and 2-item patient-reported outcome scores predicted higher response rates in induction, lower response rates in maintenance, and lower remission rates in induction and maintenance.

增加的基线克罗恩病活动指数和2项患者报告结果评分预测了诱导期较高的反应率，维持期较低的反应率，以及诱导期和维持期较低的缓解率。

Conclusions

Patient- and trial-level characteristics influence placebo rates in Crohn's disease trials.

患者和试验级别的特征会影响克罗恩病试验中的安慰剂反应率。

Careful implementation of eligibility criteria, outcome definitions, and patient stratification may reduce placebo rates.

仔细实施资格标准、结果定义和患者分层可能会降低安慰剂反应率。