Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Rheumatology, Maasstad Hospital, Rotterdam, The Netherlands.
Trials. 2020 Oct 16;21(1):862. doi: 10.1186/s13063-020-04731-2.
We present a study protocol for a randomized, double-blind, placebo-controlled trial that investigates the hypothesis if intervention in the symptomatic phase preceding clinical arthritis (clinically suspect arthralgia (CSA)) is effective in preventing progression from subclinical inflammation to clinically apparent persistent arthritis. Currently, rheumatoid arthritis (RA) can be recognized and diagnosed when arthritis (joint swelling) has become detectable at physical examination. Importantly, at this time, the immune processes have already matured, chronicity is established, and patients require long-standing treatment with disease-modifying anti-rheumatic drugs. The TREAT EARLIER trial studies the hypothesis that intervention in the symptomatic phase preceding clinical arthritis is more often successful in permanent disease modification because of less matured underlying disease processes.
A two-level definition to identify patients that are prone to develop RA is used. First, patients should have CSA and recent-onset arthralgia (< 1 year) that is suspect to progress to RA according to the expertise of the treating rheumatologist. Second, patients need to have subclinical inflammation of the hand or foot joints at 1.5 T MRI. The trial aims to recruit 230 participants from secondary care hospital settings across the south-west region of The Netherlands. Intervention will be randomly assigned and includes a single-dose of intramuscular 120 mg methylprednisolon followed by methotrexate (increasing dose to 25 mg/week orally) or placebo (both; injection and tablets) over the course of 1 year. Thereafter, participants are followed for another year. The primary endpoint is the development of clinically detectable arthritis, either fulfilling the 2010 criteria for RA or unclassified clinical arthritis of ≥ 2 joints, which persists for at least 2 weeks. DMARD-free status is a co-primary endpoint. The patient-reported outcomes functioning, along with workability and symptoms, are key secondary endpoints. Participants, caregivers (including those assessing the endpoints), and scientific staff are all blinded to the group assignment.
This proof-of-concept study is the logical consequence of pre-work on the identification of patients with CSA with MRI-detected subclinical joint inflammation. It will test the hypothesis whether intervention in patients in this early phase with the cornerstone treatment of classified RA (methotrexate) hampers the development of persistent RA and reduce the disease burden of RA.
Dutch Trial Register NL4599 (NTR4853). Registered on 20 October 2014.
我们提出了一项研究方案，这是一项随机、双盲、安慰剂对照试验，旨在验证这样一个假设，即在临床关节炎（临床可疑性关节炎（CSA））前的症状期进行干预是否能有效预防亚临床炎症向临床明显持续性关节炎的进展。目前，当关节炎（关节肿胀）在体格检查中变得可检测到时，即可诊断类风湿关节炎（RA）。重要的是，此时，免疫过程已经成熟，慢性过程已经确立，患者需要长期使用疾病修饰抗风湿药物进行治疗。EARLIER 试验研究了这样一个假设，即在临床关节炎前的症状期进行干预，由于潜在疾病过程尚未完全成熟，因此更有可能成功地进行永久性疾病改善。
使用两级定义来识别可能发展为 RA 的患者。首先，患者应具有 CSA 和近期发作的关节炎（<1 年），根据治疗风湿病专家的专业知识，这些关节炎疑似会进展为 RA。其次，患者需要在 1.5T MRI 上有手部或足部关节的亚临床炎症。该试验旨在从荷兰西南部的二级保健医院环境中招募 230 名参与者。干预将随机分配，包括单次肌内注射 120mg 甲基强的松龙，随后在 1 年内口服甲氨蝶呤（增加至 25mg/周）或安慰剂（两者均为注射和片剂）。此后，参与者再随访 1 年。主要终点是出现临床可检测到的关节炎，符合 2010 年 RA 标准或≥2 个关节的未分类临床关节炎，持续至少 2 周。无 DMARD 状态是一个共同的主要终点。患者报告的结局功能，以及工作能力和症状，是关键的次要终点。参与者、护理人员（包括评估终点的人员）和科学工作人员对分组均不知情。
这项概念验证研究是在使用 MRI 检测亚临床关节炎症识别具有 CSA 的患者的前期工作的逻辑结果。它将检验这样一个假设，即在具有分类 RA（甲氨蝶呤）基石治疗的早期阶段干预患者是否会阻碍持续性 RA 的发展，并减轻 RA 的疾病负担。
荷兰试验注册处 NL4599（NTR4853）。于 2014 年 10 月 20 日注册。
