本研究旨在调查免疫检查点抑制剂 (ICI) 试验中安慰剂报告的免疫相关不良事件 (irAE) 的患病率。我们在公共数据库中搜索了涉及恶性肿瘤患者中 ICI 与安慰剂治疗的随机临床试验 (RCT)。使用随机效应模型提取研究特征和 irAE 发生情况进行荟萃分析。报告经历任何级别和 3 至 5 级安慰剂 irAE 的患者比例；实验组中报告“假”irAE 的风险比 (RR)（定义为“假-irAE 比率”，通过将安慰剂组中记录有 irAE 的患者比例除以实验组中的患者比例来计算）。47 RCT对 30,119 名患者进行了分析。在安慰剂参与者中，报告经历任何级别和 3 至 5 级 irAE 的患者的汇总比例分别为 22.85% (17.33%-29.50%) 和 3.40% (2.35%-4.63%)。接受安慰剂治疗的患者中出现严重 irAE 的汇总比例为 0.67% (0.03%-1.91%)。因安慰剂 irAE 导致治疗中断和死亡的患者分别为 0.69% (<0.01%-1.30%) 和 0.12% (<0.01%-0.40%)。任何级别和 3 至 5 级 irAE 的假-irAE 比率分别为 0.49 和 0.28。安慰剂加非免疫治疗对照组的随机对照试验中，假-irAE 比率显着高于单独使用安慰剂的随机对照试验（任何等级：0.57 与 0.32，P < 0.001；3 至 5 级：0.36 与 0.12，P = 0.009)。我们对 ICI 随机对照试验中接受安慰剂治疗的参与者的分析记录了安慰剂 irAE 的常见发生情况。这些发现对于解释 irAE 概况、避免不适当的治疗干预非常重要。版权所有 © 2024 Elsevier Ltd。保留所有权利。

This study aims to investigate the underexplored prevalence of placebo-reported immune-related adverse events (irAEs) in immune checkpoint inhibitor (ICI) trials.We searched public databases for randomized clinical trials (RCTs) involving ICI versus placebo treatments in patients with malignancies. Study characteristics and irAEs occurrences were extracted for meta-analyses using a random-effects model.Proportions of patients reported to experience any grade and grade 3 to 5 placebo irAEs; the risk ratio (RR) of reporting 'false' irAEs in the experiment arm (defined as 'false-irAE ratio', calculated by dividing the proportion of patients documented with irAEs in the placebo arm by that in the experimental arm).47 RCTs with 30,119 patients were analyzed. The pooled proportion of patients reported to experience any grade and grade 3 to 5 irAEs among placebo participants was 22.85 % (17.33 %-29.50 %) and 3.40 % (2.35 %-4.63 %), respectively. The pooled proportion of placebo-treated patients who experienced serious irAEs was 0.67 % (0.03 %-1.91 %). Treatment discontinuation and death due to placebo irAEs occurred in 0.69 % (<0.01 %-1.30 %) and 0.12 % (<0.01 %-0.40 %) of patients, respectively. The false-irAE ratio for any grade and grade 3 to 5 irAEs were 0.49 and 0.28. The false-irAE ratio was significantly higher in RCTs with control arms of placebo plus non-immunotherapy than in those with placebo alone (any grade: 0.57 vs. 0.32, P < 0.001; grade 3 to 5: 0.36 vs. 0.12, P = 0.009).Our analyses of placebo-treated participants in ICI RCTs document the common occurrence of placebo irAEs. These findings are important for interpreting irAE profiles, avoiding inappropriate therapeutic interventions.Copyright © 2024 Elsevier Ltd. All rights reserved.