OBJECTIVE Immune checkpoint inhibitors (ICI) have revolutionized cancer outcomes but are limited by immunerelated adverse events (irAE), including rheumatic irAEs (Rh-irAE). Aging is associated with increased inflammation, referred to as "inflamm-aging". In this study, we explore the impact of age on severity, frequency, and treatment of Rh-irAEs. METHODS Adults with new Rh-irAEs after ICI exposure are followed prospectively across 10 Canadian sites as part of the CanRIO prospective cohort. In this study of patients seen between January 2020 and March 2023, we compare the severity of Rh-irAE and number of irAE between patients ≥65 years and <65 years and explore potential epidemiologic, treatment-related, and phenotypic differences between the older and younger patients. RESULTS A total of 139 patients with de novo Rh-irAEs were included, 58 in the "younger" (<65 years) and 81 in the "older" (≥65 years) group. There were no significant differences in severity of Rh-irAE (p=0.84) or number of irAEs (p=0.21), although there was a non-significant trend towards more older patients than younger patients with ≥3 irAEs (24% vs. 14%). Types of treatment for Rh-irAEs were similar between the groups. ICI continuation did not differ. Within the ICI-inflammatory arthritis (ICI-IA) subgroup, there was also no significant difference in the incidence of severe Rh-irAEs (p=0.51). CONCLUSION Similar numbers of overall irAE and severity of Rh-irAE were observed between older vs. younger patients who developed Rh-irAE after treatment with ICI therapy, suggesting that "inflamm-aging" does not play a significant role in Rh-irAEs. Larger studies are needed to explore potential differences in patient phenotypes.

中文翻译：

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年龄对风湿免疫相关不良事件的影响：加拿大免疫肿瘤学风湿病研究小组 （CanRIO） 的经验。


目的 免疫检查点抑制剂 （ICI） 彻底改变了癌症结局，但受到免疫相关不良事件 （irAE） 的限制，包括风湿性 irAE （Rh-irAE）。衰老与炎症增加有关，称为“炎症性衰老”。在这项研究中，我们探讨了年龄对 Rh-irAEs 的严重程度、频率和治疗的影响。方法 作为 CanRIO 前瞻性队列的一部分，在 10 个加拿大地点前瞻性跟踪 ICI 暴露后出现新 Rh-irAE 的成人。在这项针对 2020 年 1 月至 2023 年 3 月期间就诊的患者的研究中，我们比较了 ≥65 岁和 <65 岁患者之间 Rh-irAE 的严重程度和 irAE 数量，并探讨了老年和年轻患者之间潜在的流行病学、治疗相关和表型差异。结果 共纳入 139 例新发 Rh-irAEs 患者，其中 58 例为“年轻”（<65 岁），81 例为“老年”（≥65 岁）组。Rh-irAE 的严重程度 （p=0.84） 或 irAEs 数量 （p=0.21） 没有显著差异，尽管存在老年患者多于年轻患者 ≥3 irAEs 的趋势 （24% vs. 14%）。两组之间 Rh-irAEs 的治疗类型相似。ICI 延续没有差异。在 ICI 炎症性关节炎 （ICI-IA） 亚组中，严重 Rh-irAE 的发生率也没有显著差异 （p=0.51）。结论 在 ICI 治疗后发生 Rh-irAE 的老年患者与年轻患者之间观察到相似的总体 irAE 数量和 Rh-irAE 的严重程度，表明“炎症衰老”在 Rh-irAEs 中起不重要作用。需要更大规模的研究来探索患者表型的潜在差异。