Circulating microRNAs associated with tumour necrosis factor or fibloblast-like synoviocyte predict cartilage damage in early rheumatoid arthritis treated with methotrexate plus adalimumab: a subanalysis of the MIRACLE study.

IF 3.4 4区 医学 Q2 RHEUMATOLOGY
Yohei Hosokawa, Yusuke Yoshida, Hiroya Tamai, Shintaro Hirata, Kei Ikeda, Toshiaki Miyamoto, Hiroaki Taguchi, Chang-Fu Kuo, Kichul Shin, Keisuke Izumi, Yasushi Kondo, Hidekata Yasuoka, Masataka Kuwana, Tomonori Ishii, Hideto Kameda, Toshihisa Kojima, Masahiko Mori, Yasunori Sato, Wen-Chan Tsai, Tsutomu Takeuchi, Yuko Kaneko
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Abstract

Objectives: This study aimed to explore the potential of plasma micro-ribonucleic acids (miRNAs) in predicting joint damage in patients with rheumatoid arthritis (RA).

Methods: This subanalysis of the MIRACLE study, a randomised, open-label, non-inferiority trial, explored and compared the efficacy and safety of treatment with adalimumab (ADA), an anti-tumour necrosis factor (TNF) α, plus a maximum tolerated dose of methotrexate (MTX) with a reduced dose of MTX in early RA. Plasma levels of miRNAs (miR-143-3p, miR-146a-5p, miR-155-5p, miR-182-5p, miR-21-5p, and miR-221-3p) and serum levels of inflammatory cytokines (interleukin-6 [IL-6], vascular endothelial growth factor [VEGF]) and matrix metalloprotease-3 (MMP-3) were measured at 24 weeks. Their association with joint destruction assessed by the modified total Sharp score [mTSS] over the 24-week period were analysed.

Results: A total of 134 patients who showed an inadequate response to MTX and started treatment with ADA were included in the analyses. Logistic regression analyses revealed that higher plasma levels of miR-143-3p, miR-146a-5p, miR-21-5p, and miR-221-3p were significantly associated with increases in mTSS >0.5 points during the observation period. In particular, positive correlation was derived from the progression of joint space narrowing. In contrast, MMP-3, VEGF, and IL-6 levels were not associated with joint destruction. Cartilage damage occurred mainly in patients treated with reduced dose of MTX.

Conclusions: Higher circulating miRNA levels predicted subsequent cartilage damage in early RA treated with a TNF inhibitor in addition to MTX. Thus, the MTX dose at ADA initiation should not be reduced in patients with high microRNA levels.

与肿瘤坏死因子或成纤维细胞样滑膜细胞相关的循环microrna预测甲氨蝶呤加阿达木单抗治疗早期类风湿关节炎的软骨损伤:MIRACLE研究的一项亚分析。
目的:本研究旨在探讨血浆微核糖核酸(miRNAs)在类风湿关节炎(RA)患者关节损伤预测中的潜力。方法:这项MIRACLE研究的亚分析是一项随机、开放标签、非劣效性试验,探讨并比较了阿达利单抗(ADA)(一种抗肿瘤坏死因子(TNF) α)加最大耐受剂量甲氨蝶呤(MTX)和减少剂量甲氨蝶呤治疗早期RA的疗效和安全性。24周时测定血浆mirna (miR-143-3p、miR-146a-5p、miR-155-5p、miR-182-5p、miR-21-5p和miR-221-3p)水平和血清炎症因子(白细胞介素-6 [IL-6]、血管内皮生长因子[VEGF])和基质金属蛋白酶-3 (MMP-3)水平。在24周的时间里,用改良的总夏普评分(mTSS)来评估它们与关节破坏的关系。结果:共有134名对MTX反应不足并开始使用ADA治疗的患者被纳入分析。Logistic回归分析显示,观察期间血浆中miR-143-3p、miR-146a-5p、miR-21-5p和miR-221-3p水平升高与mTSS >.5点升高显著相关。特别是,与关节间隙变窄的进展呈正相关。相反,MMP-3、VEGF和IL-6水平与关节破坏无关。软骨损伤主要发生在减少MTX剂量的患者中。结论:较高的循环miRNA水平预测了在MTX之外使用TNF抑制剂治疗的早期RA的后续软骨损伤。因此,对于microRNA水平较高的患者,在ADA开始时不应减少MTX剂量。
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来源期刊
CiteScore
6.10
自引率
18.90%
发文量
377
审稿时长
3-6 weeks
期刊介绍: Clinical and Experimental Rheumatology is a bi-monthly international peer-reviewed journal which has been covering all clinical, experimental and translational aspects of musculoskeletal, arthritic and connective tissue diseases since 1983.
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