Immune checkpoint inhibito-induced arthralgia is tightly associated with improved overall survival in cancer patients
Immune checkpoint inhibito-induced arthralgia is tightly associated with improved overall survival in cancer patients
复制标题
免疫检查点抑制剂引起的关节痛与癌症患者总生存期的改善密切相关
DOI：
10.1093/rheumatology/keac519
复制
发表时间：
2023
期刊：
影响因子：
5.5
通讯作者：
Nakajima Hideaki,et al.
中科院分区：
文献类型：
--
作者：
Maeda Ayaka;Takase-Minegishi Kaoru;Kirino Yohei;Hamada Naoki;Kunishita Yosuke;Yoshimi Ryusuke;Horita Nobuyuki;Nakajima Hideaki;Hamada Naoki;Kirino Yohei;Nakajima Hideaki,et al.
目的随着癌症患者越来越多地使用免疫检查点抑制剂（ICIs），关节痛已成为最常见的肌肉骨骼免疫相关不良事件（irAE）。我们的目的是描述关节痛的特征及其与总生存期 (OS) 的关系。材料和方法对来自四个在线数据库的 ICI 诱发关节痛数据报告的随机对照试验 (RCT) 进行了全面调查。使用随机效应模型荟萃分析计算关节痛的比值比 (OR) 和 95% CI。个体患者数据是根据评估患有或不患有 ICI 诱发关节痛的患者的 OS 的随机对照试验重建的。我们还在横滨市立大学 (YCU) 登记处回顾性收集了 ICI 引起的关节痛的临床特征和结果数据。结果我们分析了 24 项随机对照试验中的 14 377 名患者。 ICI 引起的关节痛的 OR 为 1.37 (95% CI 1.20, 1.56)。在 YCU 登记的 369 名患者中，50 名 (13.6%) 出现 ICI 诱发的关节痛。其中，30 例有其他 ≥2 级 irAE，其发生率明显高于无关节痛的患者（OR 1.92，95% CI 1.04，3.52）。根据 irAE 类型，相对肾上腺功能不全存在显着差异（OR 3.88，95% CI 1.80，8.39）。在 YCU 登记中，有（与无）ICI 诱发关节痛的患者具有更好的 OS（对数秩，P< 0.001）。 OS 结果在癌症类型、药物和关节痛发作时间相匹配的 RCT 患者中得到验证（风险比 0.34，95% CI 0.17、0.65，P < 0.001）。 结论 如果 ICI 后出现关节痛，则可能出现另一种 irAE，例如相对肾上腺功能不全。关节痛的发生率与更好的 OS 相关，必须仔细评估 irAE 患者的病情以确定最佳治疗方案。
ObjectivesWith the increased use of immune checkpoint inhibitors (ICIs) in cancer patients, arthralgia has been the most commonly reported musculoskeletal immune-related adverse event (irAE). We aimed to characterize arthralgia and its association with overall survival (OS).Material and methodsRandomized controlled trials (RCTs) reporting on data for ICI-induced arthralgia from four online databases were comprehensively investigated. Odds ratios (ORs) with 95% CIs were calculated for arthralgia using a random-effects model meta-analysis. Individual patient data were reconstructed from RCTs assessing OS in patients with or without ICI-induced arthralgia. We also retrospectively collected data on the clinical features and outcomes of ICI-induced arthralgia in the Yokohama City University (YCU) registry.ResultsWe analysed 14 377 patients from 24 RCTs. The OR of ICI-induced arthralgia was 1.37 (95% CI 1.20, 1.56). Of the 369 patients in the YCU registry, 50 (13.6%) developed ICI-induced arthralgia. Among them, 30 had other grade ≥2 irAEs, which was noticeably more frequent than in those without arthralgia (OR 1.92, 95% CI 1.04, 3.52). By irAE types, a significant difference was found for relative adrenal insufficiency (OR 3.88, 95% CI 1.80, 8.39). In the YCU registry, patients with (vswithout) ICI-induced arthralgia had better OS (log-rank,P< 0.001). OS results were validated from RCT patients with matched cancer types, drugs, and time to arthralgia onset (hazard ratio 0.34, 95% CI 0.17, 0.65,P< 0.001).ConclusionsIf arthralgia develops after ICIs, another irAE, such as relative adrenal insufficiency, may have developed. The incidence of arthralgia was associated with better OS, and the condition of patients with irAEs must be carefully evaluated to determine optimal management.