Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Genoa, Italy; Department of Experimental Medicine (DIMES), University of Genova, Genoa, Italy.
IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Autoimmun Rev. 2024 Jul-Aug;23(7-8):103589. doi: 10.1016/j.autrev.2024.103589. Epub 2024 Aug 6.
An altered immune tolerance disturbed by immune checkpoint inhibitors (ICIs) may contribute to new-onset polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). This systematic literature review (SLR) examines the characteristics of PMR and GCA-like syndromes following anticancer treatment with ICIs, summarizing their demographic, clinical and treatment-related features to provide insights whether they differ from the idiopathic forms.
The SLR was conducted in Medline and EMBASE databases from inception to July 2024, and in the EULAR/ACR abstract database (2021-2023). ICI-induced PMR and GCA syndromes were compared to the primary forms of the diseases using data from studies that included both groups as comparators. For manuscripts lacking direct comparisons, we summarized the main findings and discussed the differences using systematic reviews or large observational studies on the primary forms.
From 1237 screened abstracts, 46 met the inclusion criteria, involving 358 patients (314 with ICI-PMR and 44 with ICI-GCA). ICI-PMR had an estimated pooled prevalence of 0.1% [95% CI: 0.07%, 0.14%] among ICI recipients and 15.9% [95% CI: 12.6%, 19.9%] among patients experiencing rheumatic immune-related adverse events. Patients with ICI-PMR had a male-to-female ratio of 1.7:1 and a mean age of 71 ± 4 years. Most cases were associated with PD1/PDL1 blockers (87%). Clinical features included inflammatory pain in the girdles (100%), though pelvic girdle involvement was under-reported in some cases (3/28 studies). Peripheral arthritis was present in 35% of patients. Laboratory tests showed normal or slightly elevated inflammatory markers in 26% of cases. Glucocorticoids (GCs) led to symptom improvement in 84% of cases although 20% required immunosuppressive treatment and 14% experienced relapses. ICI-GCA had a prevalence of 0.06% among ICI recipients, with equal gender distribution and a mean age of 71 ± 5 years. Most patients received anti-PD1/PDL1 blockers (57%). Clinical manifestations included cephalic symptoms (75%), permanent visual loss (23%) and symptoms related to large-vessel involvement (54%). High-dose GCs were effective, with 96% achieving remission, though 17% experienced relapses.
ICI-induced PMR and GCA may have distinct clinical profiles compared to idiopathic forms, with potentially milder symptoms and better treatment responses. Further studies are needed to confirm these findings and better understand the long-term outcomes and pathophysiology of these conditions.
免疫检查点抑制剂（ICIs）引起的免疫耐受改变可能导致新发性巨细胞动脉炎（GCA）和多发性肌炎（PMR）。本系统文献综述（SLR）检查了癌症治疗中使用 ICI 后 PMR 和 GCA 样综合征的特征，总结了其人口统计学、临床和治疗相关特征，以了解它们是否与特发性形式有所不同。
从 Medline 和 EMBASE 数据库到 2024 年 7 月进行了 SLR，并在 EULAR/ACR 摘要数据库（2021-2023 年）中进行了检索。使用同时包含这两种疾病的研究数据，将 ICI 诱导的 PMR 和 GCA 综合征与原发性疾病进行了比较。对于缺乏直接比较的手稿，我们总结了主要发现，并使用原发性疾病的系统评价或大型观察性研究讨论了差异。
从 1237 篇筛选出的摘要中，有 46 篇符合纳入标准，涉及 358 名患者（314 名患有 ICI-PMR 和 44 名患有 ICI-GCA）。ICI-PMR 在接受 ICI 治疗的患者中的估计患病率为 0.1% [95% CI：0.07%，0.14%]，在发生风湿免疫相关不良事件的患者中的患病率为 15.9% [95% CI：12.6%，19.9%]。患有 ICI-PMR 的患者男女比例为 1.7:1，平均年龄为 71 ± 4 岁。大多数病例与 PD1/PDL1 阻滞剂有关（87%）。临床特征包括肩胛带炎症性疼痛（100%），但在某些情况下骨盆带受累报道较少（28 项研究中的 3 项）。35%的患者存在外周关节炎。实验室检查显示 26%的病例炎症标志物正常或略有升高。84%的病例使用糖皮质激素（GCs）后症状改善，尽管 20%需要免疫抑制治疗，14%出现复发。ICI-GCA 在接受 ICI 治疗的患者中的患病率为 0.06%，性别分布均衡，平均年龄为 71 ± 5 岁。大多数患者接受抗 PD1/PDL1 阻滞剂治疗（57%）。临床表现包括头部症状（75%）、永久性视力丧失（23%）和与大血管受累相关的症状（54%）。高剂量 GCs 有效，96%的患者达到缓解，但 17%的患者复发。
与特发性疾病相比，ICI 诱导的 PMR 和 GCA 可能具有不同的临床特征，症状可能较轻，治疗反应较好。需要进一步研究以证实这些发现，并更好地了解这些疾病的长期结局和病理生理学。
