Li Ru, Zhao Jin-Xia, Su Yin, He Jing, Chen Li-Na, Gu Fei, Zhao Cheng, Deng Xue-Rong, Zhou Wei, Hao Yan-Jie, Xue Yu, Liu Hua-Xiang, Zhao Yi, Zou Qing-Hua, Liu Xiang-Yuan, Zhu Ping, Sun Ling-Yun, Zhang Zhuo-Li, Zou He-Jian, Li Xing-Fu, Liu Yi, Fang Yong-Fei, Keystone Edward, McInnes Iain B, Li Zhan-Guo
Department of Rheumatology and Immunology, Peking University People's Hospital Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing Department of Clinical Immunology, Fourth Military Medical University Xijing Hospital, Xi'an Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing Department of Rheumatology and Immunology, Fudan University Huashan Hospital, Shanghai Department of Rheumatology and Immunology, Shandong University Qilu Hospital, Jinan Department of Rheumatology and Immunology, Sichuan University West China Hospital, Chengdu Department of Rheumatology and Immunology, Third Military Medical University Southwest Hospital, Chongqing, China The Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Canada Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Medicine (Baltimore). 2016 Jul;95(28):e3968. doi: 10.1097/MD.0000000000003968.
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.
确定延长使用改善病情抗风湿药物（DMARD）强化治疗（PRINT）是否能使重症类风湿关节炎（RA）患者获得高缓解率和低复发率。
在这项多中心、随机平行治疗试验中，从9个中心招募了346例活动期RA患者（疾病活动评分（28个关节）[DAS28]（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，最长36周，直至达到缓解（DAS28≤2.6）或低疾病活动度（2.6<DAS28≤3.2）。在第2阶段，达到缓解或低疾病活动度的患者随机分为2种减量方案之一进行随访：来氟米特加羟氯喹联合用药或来氟米特单药治疗。主要终点为强化治疗期间良好的欧洲抗风湿病联盟（EULAR）反应（DAS28（ESR）<3.2且DAS28至少降低1.2）以及减量维持治疗期间的疾病状态维持率。探寻强化治疗期良好EULAR反应及维持期疾病复发的预测因素。
在12周、24周和36周时，分别有18.7%、36.9%和54.1%的患者获得良好的EULAR反应。到36周时，75.4%的患者获得了良好和中等的EULAR反应。与达到低疾病活动度且健康评估问卷评分较高（HAQ>0.5）的患者相比，达到缓解（DAS28≤2.6）且HAQ较低（≤0.5）的患者在逐渐减少DMARD治疗时的维持率显著更高（分别为P=0.046和P=0.01）。减量至联合用药而非单药治疗并无优势。
一部分接受延长强化DMARD治疗的RA患者实现了缓解。疾病减量开始时的低疾病活动度导致后续复发较少。来氟米特作为单药治疗是一种良好的维持治疗药物。
