Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study
Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study
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DOI：
10.1016/j.jaut.2019.06.009
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发表时间：
2019-12-01
影响因子：
12.8
通讯作者：
Isaacs, John D.
中科院分区：
文献类型：
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作者：
Baker, Kenneth F.;Skelton, Andrew J.;Isaacs, John D.
背景：许多类风湿性关节炎（RA）患者通过现代治疗策略获得了疾病缓解。然而，达到这种状态后，没有任何测试可以预测何时停止治疗将导致无药物缓解而不是病情加重。我们的目的是确定 RA 无药物缓解的预测因子。方法：类风湿关节炎缓解的生物标志物 (BioRRA) 研究是一项独特的、前瞻性的、干预性队列研究，研究的是完全和突然停止传统合成缓解病情抗风湿药物 (DMARD)。病程至少 12 个月且处于临床和超声缓解状态的 RA 患者停用 DMARD，并接受为期 6 个月的监测。主要结局是发作时间，定义为 28 个关节中 C 反应蛋白 (DAS28-CRP) >= 2.4 的疾病活动评分。分别通过 Cox 回归和接受者操作特征 (ROC) 分析，评估基线临床和超声测量、循环炎症生物标志物和外周 CD4(+) T 细胞基因表达预测发作时间和发作/缓解状态的能力。结果：23/44 (52%) 符合条件的患者在中位数 (IQR) 为 48 后出现关节炎发作。 DMARD 停用后 (31.5-86.5) 天。包含五个基线变量（三个转录本 [FAM102B、ENSG00000228010、ENSG00000227070]、一种细胞因子 [白介素-27]、一种临床 [布尔缓解]）的综合评分区分了未来发作与无药物缓解，ROC 曲线下面积为 0.96 (95% CI 0.91-1.00)，灵敏度为 0.91 (0.78-1.00) 和特异性 0.95 (0.84-1.00)。结论：我们为 RA 无药物缓解的预测因子提供了概念验证证据。如果经过验证，这些生物标志物可以帮助个性化免疫抑制剂的戒断：治疗范式的转变，从而带来患者和经济效益。
Background: Many patients with rheumatoid arthritis (RA) achieve disease remission with modem treatment strategies. However, having achieved this state, there are no tests that predict when withdrawal of therapy will result in drug-free remission rather than flare. We aimed to identify predictors of drug-free remission in RA.Methods: The Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study was a unique, prospective, interventional cohort study of complete and abrupt cessation of conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Patients with RA of at least 12 months duration and in clinical and ultrasound remission discontinued DMARDs and were monitored for six months. The primary outcome was time-to-flare, defined as disease activity score in 28 joints with C-reactive protein (DAS28-CRP) >= 2.4. Baseline clinical and ultrasound measures, circulating inflammatory biomarkers, and peripheral CD4(+) T cell gene expression were assessed for their ability to predict time-to-flare and flare/remission status by Cox regression and receiver-operating characteristic (ROC) analysis respectively.Results: 23/44 (52%) eligible patients experienced an arthritis flare after a median (IQR) of 48 (31.5-86.5) days following DMARD cessation. A composite score incorporating five baseline variables (three transcripts [FAM102B, ENSG00000228010, ENSG00000227070], one cytokine [interleukin-27], one clinical [Boolean remission]) differentiated future flare from drug-free remission with an area under the ROC curve of 0.96 (95% CI 0.91-1.00), sensitivity 0.91 (0.78-1.00) and specificity 0.95 (0.84-1.00).Conclusion: We provide proof-of-concept evidence for predictors of drug-free remission in RA. If validated, these biomarkers could help to personalize immunosuppressant withdrawal: a therapy paradigm shift with ensuing patient and economic benefits.