title: High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT): A multicenter randomized clinical trial.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
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authors.forename: Jin-Xia
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authors.forename: Li-Na
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authors.lastname: Zhao
authors.forename: Xue-Rong
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authors.lastname: Deng
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: Hao
authors.forename: Yu
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authors.lastname: Xue
authors.forename: Hua-Xiang
authors.initials: HX
authors.lastname: Liu
authors.forename: Yi
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authors.lastname: Zhao
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Zou
authors.forename: Xiang-Yuan
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authors.lastname: Liu
authors.forename: Ping
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authors.lastname: Zhu
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Sun
authors.forename: Zhuo-Li
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authors.lastname: Zhang
authors.forename: He-Jian
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authors.lastname: Zou
authors.forename: Xing-Fu
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authors.lastname: Li
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mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001799:Blood Sedimentation; D002681:China; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents