Rheumatology Department, Centre Hospitalier Universitaire, Bordeaux, Aquitaine, France.
Pulmonology Department, Centre Hospitalier Universitaire, Bordeaux, Aquitaine, France.
Ann Rheum Dis. 2018 Mar;77(3):393-398. doi: 10.1136/annrheumdis-2017-212257. Epub 2017 Nov 16.
To evaluate the prevalence and type of rheumatic immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs), as well as the correlation with tumour response.
This was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs and tumour response was assessed on a regular basis. Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management.
From September 2015 to May 2017, 524 patients received ICIs and 35 were referred to the department of rheumatology (6.6%). All but one of the rheumatic irAEs occurred with anti-programmed cell death protein 1(PD-1)/PD-1 ligand 1(PD-L1) antibodies, with a median exposure time of 70 days. There were two distinct clinical presentations: (1) inflammatory arthritis (3.8%) mimicking either rheumatoid arthritis (n=7), polymyalgia rheumatica (n=11) or psoriatic arthritis (n=2) and (2) non-inflammatory musculoskeletal conditions (2.8%; n=15). One patient with rheumatoid arthritis was anti-cyclic citrullinated peptide (anti-CCP) positive. Nineteen patients required glucocorticoids, and methotrexate was started in two patients. Non-inflammatory disorders were managed with non-steroidal anti-inflammatory drugs, analgesics and/or physiotherapy. ICI treatment was pursued in all but one patient. Patients with rheumatic irAEs had a higher tumour response rate compared with patients without irAEs (85.7% vs 35.3%; P<0.0001).
Since ICIs are used with increasing frequency, knowledge of rheumatic irAEs and their management is of major interest. All patients were responsive either to low-to-moderate doses of prednisone or symptomatic therapies and did not require ICI discontinuation. Furthermore, tumour response was significantly higher in patients who experienced rheumatic irAEs.
评估接受免疫检查点抑制剂(ICI)治疗的患者中风湿免疫相关不良事件(irAEs)的发生率和类型,以及与肿瘤应答的相关性。
这是一项单中心前瞻性观察性研究,纳入了所有接受 ICI 治疗的癌症患者。定期评估 irAEs 和肿瘤应答情况。出现肌肉骨骼症状的患者被转诊至风湿科进行临床评估和管理。
2015 年 9 月至 2017 年 5 月,524 例患者接受了 ICI 治疗,其中 35 例(6.6%)被转诊至风湿科。除 1 例外,所有风湿免疫相关不良事件均发生于抗程序性细胞死亡蛋白 1(PD-1)/PD-1 配体 1(PD-L1)抗体治疗时,中位暴露时间为 70 天。存在两种不同的临床表现:(1)炎症性关节炎(3.8%),类似类风湿关节炎(n=7)、巨细胞动脉炎(n=11)或银屑病关节炎(n=2);(2)非炎症性肌肉骨骼疾病(2.8%;n=15)。1 例类风湿关节炎患者抗环瓜氨酸肽(anti-CCP)阳性。19 例患者需要使用糖皮质激素,2 例患者开始使用甲氨蝶呤。非炎症性疾病通过非甾体抗炎药、镇痛药和/或物理疗法进行治疗。除 1 例外,所有患者均继续接受 ICI 治疗。发生风湿免疫相关不良事件的患者肿瘤应答率高于未发生不良事件的患者(85.7%比 35.3%;P<0.0001)。
随着 ICI 的应用日益增多,了解风湿免疫相关不良事件及其管理至关重要。所有患者对低至中等剂量的泼尼松或对症治疗均有反应,且无需停止 ICI 治疗。此外,发生风湿免疫相关不良事件的患者肿瘤应答率显著更高。