Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques.
Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques.
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DOI：
10.1136/annrheumdis-2015-208267
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发表时间：
2016-06
影响因子：
27.4
通讯作者：
Wilkinson B
中科院分区：
文献类型：
--
作者：
Conaghan PG;Østergaard M;Bowes MA;Wu C;Fuerst T;van der Heijde D;Irazoque-Palazuelos F;Soto-Raices O;Hrycaj P;Xie Z;Zhang R;Wyman BT;Bradley JD;Soma K;Wilkinson B
探讨托法替尼（一种治疗类风湿性关节炎（RA）的口服Janus激酶抑制剂）联合或不联合甲氨蝶呤（MTX）对MTX初治的早期活动性RA和食指腕或手部滑膜炎成人患者MRI终点的影响。在这项探索性、II期、随机化、双盲、平行组研究中，患者接受托法替布10 mg每日两次+ MTX、托法替布10 mg每日两次+安慰剂（托法替布单药治疗）或MTX +安慰剂（MTX单药治疗）治疗1年。 使用重复测量的混合效应模型评估MRI终点（流变学临床试验RA MRI评分（RAMRIS）、定量RAMRIS（RAMRIQ）和动态对比增强（DCE）MRI的结局指标）。p<0.05（相对于MTX单药治疗）的治疗差异被认为是显著的。共有109例患者接受随机化和治疗。托法替尼+ MTX组第6个月RAMRIS骨髓水肿（BME）的治疗差异为−1.55（90% CI −2.52至−0.58），托法替尼单药治疗组为−1.74（−2.72至−0.76）（均为p<0.01 vs MTX单药治疗）。托法替尼+ MTX组第3个月RAMRIS滑膜炎的数值改善为−0.63（−1.58至0.31），托法替尼单药治疗组为−0.52（−1.46至0.41）（与MTX单药治疗相比，p均>0.05）。第3个月时，RAMRIQ滑膜炎的治疗差异具有统计学显著性，与DCE MRI结果一致。与MTX单药治疗相比，两个托法替尼组在第6个月和第12个月的RAMRIS和RAMRIQ糜烂性损伤恶化较少。这些结果使用三种不同的MRI技术提供了一致的证据，表明托法替尼治疗导致炎症早期减轻并抑制结构损伤的进展。NCT01164579。
To explore the effects of tofacitinib—an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)—with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand. In this exploratory, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score (RAMRIS), quantitative RAMRIS (RAMRIQ) and dynamic contrast-enhanced (DCE) MRI) were assessed using a mixed-effect model for repeated measures. Treatment differences with p<0.05 (vs MTX monotherapy) were considered significant. In total, 109 patients were randomised and treated. Treatment differences in RAMRIS bone marrow oedema (BME) at month 6 were −1.55 (90% CI −2.52 to −0.58) for tofacitinib + MTX and −1.74 (−2.72 to −0.76) for tofacitinib monotherapy (both p<0.01 vs MTX monotherapy). Numerical improvements in RAMRIS synovitis at month 3 were −0.63 (−1.58 to 0.31) for tofacitinib + MTX and −0.52 (−1.46 to 0.41) for tofacitinib monotherapy (both p>0.05 vs MTX monotherapy). Treatment differences in RAMRIQ synovitis were statistically significant at month 3, consistent with DCE MRI findings. Less deterioration of RAMRIS and RAMRIQ erosive damage was seen at months 6 and 12 in both tofacitinib groups versus MTX monotherapy. These results provide consistent evidence using three different MRI technologies that tofacitinib treatment leads to early reduction of inflammation and inhibits progression of structural damage. NCT01164579.