Importance Limited information is available on the safety of a rechallenge with an immune checkpoint inhibitor (ICI) after an immune-related adverse event (irAE).

Objective To identify the recurrence rate of the same irAE that prompted discontinuation of ICI therapy after an ICI rechallenge in patients with cancer and to identify the clinical features associated with such recurrences.

Design, Setting, and Participants This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase, which contains case reports from more than 130 countries. Case reports were extracted from database inception (1967) to September 1, 2019. All consecutive ICI cases with at least 1 associated irAE were included.

Main Outcomes and Measures The primary outcome was the rate of recurrence of the initial irAE after an ICI rechallenge. Secondary outcomes included the factors associated with the recurrence after a rechallenge among informative rechallenges, the recurrence rate according to the ICI regimen (anti–programmed cell death 1 or anti–programmed cell death ligand 1 monotherapy, anti–cytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy), and the rate of occurrence of a different irAE after a rechallenge.

Results A total of 24 079 irAE cases associated with at least 1 ICI were identified. Among the irAEs, 452 of 6123 irAEs associated with ICI rechallenges (7.4%) were informative rechallenges. One hundred thirty recurrences (28.8%; 95% CI, 24.8-33.1) of the initial irAE were observed. In a rechallenge, colitis (reporting odds ratio [OR], 1.77; 95% CI, 1.14-2.75; P = .01), hepatitis (reporting OR, 3.38; 95% CI, 1.31-8.74; P = .01), and pneumonitis (reporting OR, 2.26; 95% CI, 1.18-4.32; P = .01) were associated with a higher recurrence rate, whereas adrenal events were associated with a lower recurrence rate (reporting OR, 0.33; 95% CI, 0.13-0.86; P = .03) compared with other irAEs.

Conclusions and Relevance This cohort study found a 28.8% recurrence rate of the same irAE associated with the discontinuation of ICI therapy after a rechallenge with the same ICI. Resuming ICI therapy could be considered for select patients, with appropriate monitoring and use of standard treatment algorithms to identify and treat toxic effects.

重要性 关于免疫相关不良事件 (irAE) 后再次使用免疫检查点抑制剂 (ICI) 的安全性的信息有限。

目的 确定在癌症患者再次接受 ICI 治疗后导致停止 ICI 治疗的相同 irAE 的复发率，并确定与此类复发相关的临床特征。

设计、设置和参与者 这项观察性、横断面、药物警戒队列研究检查了来自世界卫生组织数据库 VigiBase 的个别病例安全报告，该数据库包含来自 130 多个国家的病例报告。病例报告从数据库开始（1967 年）到 2019 年 9 月 1 日提取。包括所有至少有 1 个相关 irAE 的连续 ICI 病例。

主要结果和测量 主要结果是 ICI 再激发后初始 irAE 的复发率。次要结局包括信息性再挑战中与再挑战后复发相关的因素、根据 ICI 方案的复发率（抗程序性细胞死亡 1 或抗程序性细胞死亡配体 1 单一疗法、抗细胞毒性 T 淋巴细胞抗原 4单药治疗或联合治疗），以及再次激发后不同 irAE 的发生率。

结果 共确定了 24 079 例与至少 1 个 ICI 相关的 irAE 病例。在 irAE 中，与 ICI 再挑战相关的 6123 个 irAE 中有 452 个（7.4%）是信息性再挑战。观察到初始 irAE 的 130 次复发（28.8%；95% CI，24.8-33.1）。在再次挑战中，结肠炎（报告比值比 [OR]，1.77；95% CI，1.14-2.75；P  = .01），肝炎（报告 OR，3.38；95% CI，1.31-8.74；P  = .01），和肺炎（报告 OR，2.26；95% CI，1.18-4.32；P  = .01）与较高的复发率相关，而肾上腺事件与较低的复发率相关（报告 OR，0.33；95% CI，0.13 -0.86；P  = .03）与其他 irAE 相比。

结论和相关性 该队列研究发现，相同 irAE 的复发率为 28.8%，与再次使用相同 ICI 治疗后停止 ICI 治疗相关。可以考虑对选定的患者恢复 ICI 治疗，并通过适当的监测和使用标准治疗算法来识别和治疗毒性作用。