Introduction

Recent studies reveal that there is no difference in the efficacy of immune checkpoint inhibitors (ICIs) between younger adults and older adults. However, it remains unclear whether age is a risk factor for immune-related adverse events (irAEs).

Materials and methods

To analyze the association between irAEs and age based on data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database between January 2004 and December 2020, we performed a case/noncase study on ICI-related adverse events. Cases were defined as adverse event cases with ICI therapy and irAEs, and noncases were defined as adverse event cases with ICI therapy and without irAEs. One case was matched to a noncase using the sex, reporter, report year, and type of ICI regimen. The reporting odds ratios (RORs) were used to assess the disproportionality of irAEs between older adults (≥65 years) and younger adults (<65 years).

Results

The study shows that compared with younger adults, the ROR of older adults was 1.12 (95% confidence interval [CI]: 1.08–1.16) and 1.18 (95% CI: 1.14–1.23) before and after matching, respectively. The signal of age-related irAEs was detected in patients treated with ICI monotherapy but not in patients treated with combination therapy. Further analysis revealed a spectrum of age-related toxicities including cardiovascular toxicities, lung toxicities, musculoskeletal toxicities, nervous system toxicities, renal toxicities, and skin toxicities.

Conclusion

In this analysis performed based on the FAERS, irAE cases were more likely to be reported in older adults. Our pharmacovigilance study complements the safety data of clinical trials. Further studies are expected to explore the underlying reasons for irAEs in older adults.

中文翻译：

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老年人免疫相关不良事件：FDA 不良事件报告系统的数据挖掘

介绍

最近的研究表明，免疫检查点抑制剂 (ICI) 在年轻人和老年人之间的疗效没有差异。然而，尚不清楚年龄是否是免疫相关不良事件（irAEs）的危险因素。

材料和方法

为了根据 2004 年 1 月至 2020 年 12 月期间美国食品和药物管理局不良事件报告系统 (FAERS) 数据库中的数据分析 irAE 与年龄之间的关联，我们对 ICI 相关的不良事件进行了案例/非案例研究。病例被定义为有 ICI 治疗和 irAEs 的不良事件病例，非病例被定义为有 ICI 治疗和没有 irAEs 的不良事件病例。使用性别、报告人、报告年份和 ICI 方案类型将一个病例与非病例匹配。报告优势比 (ROR) 用于评估老年人（≥65 岁）和年轻人（<65 岁）之间 irAE 的不成比例。

结果

研究表明，与年轻人相比，老年人匹配前后的 ROR 分别为 1.12（95% CI：1.08-1.16）和 1.18（95% CI：1.14-1.23）。在接受 ICI 单药治疗的患者中检测到与年龄相关的 irAE 信号，但在接受联合治疗的患者中未检测到。进一步的分析揭示了一系列与年龄相关的毒性，包括心血管毒性、肺毒性、肌肉骨骼毒性、神经系统毒性、肾毒性和皮肤毒性。

结论

在这项基于 FAERS 的分析中，irAE 病例更有可能在老年人中报告。我们的药物警戒研究补充了临床试验的安全性数据。预计进一步的研究将探讨老年人 irAEs 的根本原因。