High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT): A multicenter randomized clinical trial.
High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT): A multicenter randomized clinical trial.
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DOI：
10.1097/md.0000000000003968
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发表时间：
2016-07
期刊：
影响因子：
1.6
通讯作者：
Li ZG
中科院分区：
文献类型：
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作者：
Li R;Zhao JX;Su Y;He J;Chen LN;Gu F;Zhao C;Deng XR;Zhou W;Hao YJ;Xue Y;Liu HX;Zhao Y;Zou QH;Liu XY;Zhu P;Sun LY;Zhang ZL;Zou HJ;Li XF;Liu Y;Fang YF;Keystone E;McInnes IB;Li ZG
确定长期强化疾病缓解抗风湿药物（DMARD）治疗（PRINT）是否导致严重类风湿关节炎（RA）患者的高缓解率和低复发率。在这项多中心、随机和平行治疗试验中，从9个中心招募了346例活动性RA患者（疾病活动性评分（28个关节）[DAS 28]（红细胞沉降率[ESR]）> 5.1）。在第1阶段，患者接受甲氨蝶呤、来氟米特和羟氯喹强化治疗，长达36周，直至达到缓解（DAS 28 ≤ 2.6）或低疾病活动度（2.6 <DAS 28 ≤ 3.2）。在第2阶段，达到缓解或低疾病活动度的患者被随机随访至2个递减方案之一：来氟米特+羟氯喹联合治疗或来氟米特单药治疗。主要终点是强化治疗期间良好的欧洲抗风湿联盟（EULAR）反应（DAS 28（ESR）< 3.2，DAS 28降低至少1.2）和降压维持治疗期间的疾病状态留存率。寻找强化治疗期良好EULAR应答和维持治疗期疾病发作的预测因子。在12、24和36周时，分别有18.7%、36.9%和54.1%的患者实现了良好的EULAR缓解。到36周时，75.4%的患者达到良好和中度EULAR反应。与达到低疾病活动度和高健康评估问卷（HAQ > 0.5）的患者相比，达到缓解（DAS 28 ≤ 2.6）和低HAQ（≤ 0.5）的患者在逐渐减少DMARDs治疗时的留存率显著更高（分别为P = 0.046和P = 0.01）。与单药治疗相比，逐渐减量至联合治疗没有优势。部分接受长期强化DMARD治疗的RA患者获得缓解。疾病逐渐减弱开始时的低疾病活动导致随后的爆发较少。来氟米特作为单药治疗是一种良好的维持治疗。
To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA). In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) > 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ≤ 2.6) or a low disease activity (2.6 < DAS28 ≤ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) < 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought. A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ > 0.5), patients achieving remission (DAS28 ≤ 2.6) and low HAQ (≤ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy. Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent flares. Leflunomide is a good maintenance treatment as single treatment.