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更高的检查点抑制剂关节炎疾病活动度可能与癌症进展相关:一项观察性登记研究的结果

Higher Checkpoint Inhibitor Arthritis Disease Activity may be Associated With Cancer Progression: Results From an Observational Registry.

作者信息

Chan Karmela Kim, Tirpack Aidan, Vitone Gregory, Benson Caroline, Nguyen Joseph, Ghosh Nilasha, Jannat-Khah Deanna, Bykerk Vivian, Bass Anne R

机构信息

Hospital for Special Surgery, New York, New York and Memorial Sloan Kettering Cancer Center, New York, New York and Weill Cornell Medical College, New York, New York.

Hospital for Special Surgery, New York, New York.

出版信息

ACR Open Rheumatol. 2020 Oct;2(10):595-604. doi: 10.1002/acr2.11181. Epub 2020 Oct 3.

Abstract

OBJECTIVE

To describe clinical features associated with cancer outcomes of patients with immune checkpoint inhibitor (ICI)-associated arthritis.

METHODS

Observational study of patients with ICI-arthritis enrolled in a single-center registry. Arthritis phenotype and activity, medications, and cancer status were recorded at every visit. We used descriptive statistic, and Kaplan-Meier curves using two-sided log-rank test and Cox regression analysis were used to identify factors associated with cancer progression-free survival (PFS).

RESULTS

Forty-two patients with ICI-arthritis were followed for a median (interquartile range [IQR]) of 7.4 (1.7, 14.7) months. Fifty-seven percent were female, 33% had melanoma, and 69% received anti-programmed death ligand 1 monotherapy. Median time from ICI initiation to arthritis onset was 2.8 (0.8, 11.2) months. Sixty-two percent had a rheumatoid arthritis (RA)-like small-joint presentation; 27% of all patients were rheumatoid factor and/or cyclic citrullinated peptide positive. Median (IQR) Clinical Disease Activity Index (CDAI) on presentation was 15 (8, 24); 62% required systemic glucocorticoids, 55% required disease-modifying antirheumatic drugs (DMARDs), and 69% had ongoing arthritis at 6 months. Arthritis led to ICI discontinuation in five patients. In univariate analysis, baseline CDAI, DMARD use, earlier arthritis onset, and longer duration of follow-up were associated with shorter PFS. In multivariable Cox regression analysis controlling for DMARD use and time to arthritis onset, CDAI was a significant predictor of cancer progression (hazard ratio 1.09, 95% confidence interval [CI] 1.00-1.19, P = 0.05) CONCLUSION: ICI-arthritis most commonly presents with an RA-like phenotype. High disease activity, as measured by CDAI, may portend cancer progression.

摘要

目的

描述免疫检查点抑制剂(ICI)相关关节炎患者的癌症预后相关临床特征。

方法

对纳入单中心登记处的ICI关节炎患者进行观察性研究。每次就诊时记录关节炎表型和活动度、用药情况及癌症状态。我们使用描述性统计方法,并采用双侧对数秩检验的Kaplan-Meier曲线和Cox回归分析来确定与无癌进展生存期(PFS)相关的因素。

结果

42例ICI关节炎患者的中位(四分位间距[IQR])随访时间为7.4(1.7,14.7)个月。57%为女性,33%患有黑色素瘤,69%接受抗程序性死亡配体1单药治疗。从开始使用ICI到关节炎发作的中位时间为2.8(0.8,11.2)个月。62%表现为类风湿关节炎(RA)样小关节症状;所有患者中27%类风湿因子和/或环瓜氨酸肽呈阳性。就诊时临床疾病活动指数(CDAI)的中位(IQR)值为15(8,24);62%的患者需要全身使用糖皮质激素,55%需要使用改善病情抗风湿药(DMARDs),69%在6个月时仍有关节炎。关节炎导致5例患者停用ICI。单因素分析中,基线CDAI、DMARD使用情况、关节炎发作较早及随访时间较长与较短的PFS相关。在控制DMARD使用情况及关节炎发作时间的多变量Cox回归分析中,CDAI是癌症进展的显著预测因素(风险比1.09,95%置信区间[CI] 1.00 - 1.19,P = 0.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aff3/7571396/95d5bad27188/ACR2-2-595-g001.jpg

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