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Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study.
Journal of Autoimmunity ( IF 12.8 ) Pub Date : 2019-07-04 , DOI: 10.1016/j.jaut.2019.06.009
Kenneth F Baker 1 , Andrew J Skelton 2 , Dennis W Lendrem 1 , Adam Scadeng 3 , Ben Thompson 1 , Arthur G Pratt 1 , John D Isaacs 1
Affiliation  

BACKGROUND Many patients with rheumatoid arthritis (RA) achieve disease remission with modern 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 anti-rheumatic 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.

中文翻译:

预测类风湿关节炎的无药物缓解:一项前瞻性干预队列研究。

背景 许多类风湿性关节炎 (RA) 患者通过现代治疗策略实现了疾病缓解。然而,在达到这种状态后,没有测试可以预测何时停止治疗会导致无药物缓解而不是突然发作。我们旨在确定 RA 无药物缓解的预测因子。方法 类风湿性关节炎缓解的生物标志物 (BioRRA) 研究是一项独特的、前瞻性的、介入性队列研究,旨在完全和突然停止常规合成的改善疾病的抗风湿药物 (DMARDs)。患有至少 12 个月持续时间和临床和超声缓解的 RA 患者停止使用 DMARD,并进行了 6 个月的监测。主要结果是发作时间,定义为 28 个关节的 C 反应蛋白 (DAS28-CRP) ≥ 2.4 的疾病活动评分。基线临床和超声测量、循环炎症生物标志物和外周 CD4+ T 细胞基因表达分别通过 Cox 回归和接受者操作特征 (ROC) 分析评估其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 DMARD 停止后中位 (IQR) 48 (31.5-86.5) 天后出现关节炎发作。包含五个基线变量(三个转录本 [FAM102B、ENSG00000228010、ENSG00000227070]、一个细胞因子 [interleukin-27]、一个临床 [布尔缓解])的综合评分将未来的发作与无药物缓解区分开来,ROC 曲线下面积为 0.96 (95% CI 0.91-1.00),敏感性 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。如果得到验证,这些生物标志物可能有助于个性化免疫抑制剂的戒断:一种治疗范式的转变,随之而来的是患者和经济利益。
更新日期:2019-11-18
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