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抗 PD-1 抑制剂治疗患者的风湿免疫相关不良事件:肌炎综合征伴筋膜炎作为免疫治疗的一种新并发症。

Rheumatic immune-related adverse events in patients on anti-PD-1 inhibitors: Fasciitis with myositis syndrome as a new complication of immunotherapy.

机构信息

Department of Rheumatology, Hospital Universitario de Bellvitge-IDIBELL, Barcelona, Spain.

Department of Rheumatology, Hospital Universitario de Bellvitge-IDIBELL, Barcelona, Spain.

出版信息

Autoimmun Rev. 2018 Oct;17(10):1040-1045. doi: 10.1016/j.autrev.2018.05.002. Epub 2018 Aug 10.

Abstract

OBJECTIVE

To evaluate the prevalence and type of rheumatic immune-related adverse events (IRAEs) in patients receiving programmed cell death protein-1 (PD-1) inhibitors.

METHODS

This is a single-center prospective observational study, including all cancer patients receiving PD-1 inhibitors between January 2016 and January 2018.

RESULTS

During the period analyzed, we evaluated a total of 11 patients. No patient had pre-existing rheumatic or autoimmune disease. In this period, a total of 220 patients were treated with PD1 inhibitors in our center; therefore, the estimated minimum prevalence of rheumatic IRAEs related to these therapies in our population was 5%. The rheumatic IRAEs evaluated included 5 cases of oligo- or polyarthritis, 1 with a polymialgia rheumatica-type syndrome, 2 cases of immunotherapy-induced sicca syndrome, 2 patients who presented symptomatic inflammatory myositis with fasciitis in lower extremities, and 1 patient with a paraneoplastic acral vascular syndrome. The median time to IRAE after anti-PD1 exposure was 8 weeks (range: 2-24). In 5 patients, immunotherapy was discontinued (due to the adverse effect in three and cancer progression in two). In general terms the symptoms resolved completely with symptomatic treatment. Disease-modifying antirheumatic drugs were needed for 2 patients.

CONCLUSION

Rheumatic IRAEs should be kept in mind during the follow-up and evaluation of patients treated with PD-1 inhibitors. The concomitant development of symptomatic inflammatory myositis with fasciitis in lower extremities appears to be a new adverse effect of anti-PD-1 immunotherapy. Additional studies are needed to determine how to adequately control and manage these complications.

摘要

目的

评估接受程序性死亡蛋白-1(PD-1)抑制剂治疗的患者发生风湿免疫相关不良事件(IRAEs)的患病率和类型。

方法

这是一项单中心前瞻性观察性研究,纳入 2016 年 1 月至 2018 年 1 月期间接受 PD-1 抑制剂治疗的所有癌症患者。

结果

在分析期间,我们共评估了 11 例患者。所有患者均无既往风湿性或自身免疫性疾病。在此期间,共有 220 例患者在我们中心接受 PD1 抑制剂治疗;因此,我们人群中与这些治疗相关的风湿性 IRAEs 的估计最低患病率为 5%。评估的风湿性 IRAEs 包括 5 例寡关节炎或多关节炎,1 例多发性肌痛样综合征,2 例免疫治疗引起的干燥综合征,2 例有症状的炎症性肌病伴下肢筋膜炎症,1 例副肿瘤性肢端血管综合征。抗 PD1 暴露后 IRAE 的中位时间为 8 周(范围:2-24 周)。5 例患者停止免疫治疗(因不良反应 3 例,癌症进展 2 例)。一般而言,症状通过对症治疗完全缓解。2 例患者需要使用疾病修饰抗风湿药物。

结论

在接受 PD-1 抑制剂治疗的患者的随访和评估中应牢记风湿性 IRAEs。下肢伴筋膜炎症的有症状炎症性肌病的同时发生似乎是抗 PD-1 免疫治疗的一种新的不良反应。需要进一步研究以确定如何充分控制和管理这些并发症。

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