Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): a randomised, double-blind, placebo-controlled, proof-of-concept trial

医学 类风湿性关节炎 安慰剂 关节炎 内科学 临床终点 痹症科 物理疗法 甲氨蝶呤 临床试验 随机对照试验 亚临床感染 外科 替代医学 病理
作者
Doortje I Krijbolder,M. Verstappen,Bastiaan T van Dijk,Yousra J. Dakkak,L.E. Burgers,Aleid C. Boer,Yune Jung Park,Marianne E de Witt-Luth,Karen Visser,Marc R. Kok,Esmeralda T. H. Molenaar,Pascal H P de Jong,Stefan Böhringer,T. Huizinga,Cornelia F Allaart,Ellis Niemantsverdriet,Annette H M van der Helm–van Mil
出处
期刊:The Lancet [Elsevier BV]
卷期号:400 (10348): 283-294 被引量:97
标识
DOI:10.1016/s0140-6736(22)01193-x
摘要

Rheumatoid arthritis is the most common autoimmune disease worldwide and requires long-term treatment to suppress inflammation. Currently, treatment is started when arthritis is clinically apparent. We aimed to evaluate whether earlier intervention, in the preceding phase of arthralgia and subclinical joint inflammation, could prevent the development of clinical arthritis or reduce the disease burden.We conducted a randomised, double-blind, placebo-controlled, proof-of-concept-trial at the Leiden University Medical Centre, Leiden, Netherlands. Adults aged 18 years or older with arthralgia clinically suspected of progressing to rheumatoid arthritis and MRI-detected subclinical joint inflammation were eligible for enrolment across 13 rheumatology outpatient clinics in the southwest region of the Netherlands and randomly assigned (1:1) to a single intramuscular glucocorticoid injection (120 mg) and a 1-year course of oral methotrexate (up to 25 mg/week), or placebo (single injection and tablets for 1 year). Participants and investigators were masked to group assignment. Follow-up continued for 1 year after the end of the 1-year treatment period. The primary endpoint was development of clinical arthritis (fulfilling the 2010 rheumatoid arthritis classification criteria or involving two or more joints) that persisted for at least 2 weeks. Patient-reported physical functioning, symptoms, and work productivity were secondary endpoints, which were measured every 4 months. Additionally, the course of MRI-detected inflammation was studied. All participants entered the intention-to-treat analysis. This trial is registered with EudraCT, 2014-004472-35, and the Netherlands Trial Register, NTR4853-trial-NL4599.Between April 16, 2015, and Sept 11, 2019, 901 patients were assessed for eligibility and 236 were enrolled and randomly assigned to active treatment (n=119) or placebo (n=117). At 2 years, the frequency of the primary endpoint was similar between the groups (23 [19%] of 119 participants in the treatment group vs 21 [18%] of 117 in the placebo group; hazard ratio 0·81, 95% CI 0·45 to 1·48). Physical functioning improved more in the treatment group during the first 4 months and remained better than in the placebo group (mean between-group difference in Health Assessment Questionnaire disability index over 2 years: -0·09, 95% CI -0·16 to -0·03; p=0·0042). Similarly, pain (on scale 0-100, mean between-group difference: -8, 95% CI -12 to -4; p<0·0001), morning stiffness of joints (-12, -16 to -8; p<0·0001), presenteeism (-8%, -13 to -3; p=0·0007), and MRI-detected joint inflammation (-1·4 points, -2·0 to -0·9; p<0·0001) showed sustained improvement in the treatment group compared with the placebo group. The number of serious adverse events was equal in both groups; adverse events were consistent with the known safety profile for methotrexate.Methotrexate, the cornerstone treatment of rheumatoid arthritis, initiated at the pre-arthritis stage of symptoms and subclinical inflammation, did not prevent the development of clinical arthritis, but modified the disease course as shown by sustained improvement in MRI-detected inflammation, related symptoms, and impairments compared with placebo.Dutch Research Council (NWO; Dutch Arthritis Society).
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
2秒前
4秒前
Owen应助张狗蛋采纳,获得10
6秒前
7秒前
8秒前
11秒前
zh完成签到,获得积分10
11秒前
焱焱不忘完成签到,获得积分0
11秒前
12秒前
随风发布了新的文献求助10
13秒前
14秒前
14秒前
科研大圣完成签到,获得积分10
14秒前
15秒前
博修发布了新的文献求助10
16秒前
桐桐应助Kurt采纳,获得10
17秒前
18秒前
坦率大米发布了新的文献求助10
19秒前
joy发布了新的文献求助10
20秒前
张狗蛋发布了新的文献求助10
21秒前
Neyra完成签到,获得积分10
21秒前
jawa完成签到 ,获得积分10
21秒前
joy完成签到,获得积分20
24秒前
研友_ZGR0jn完成签到,获得积分10
24秒前
燃燃发布了新的文献求助10
25秒前
swimming完成签到 ,获得积分10
26秒前
27秒前
蓝色斑马发布了新的文献求助10
29秒前
思源应助痴情的寒云采纳,获得10
31秒前
31秒前
无心的天真完成签到 ,获得积分10
32秒前
桐桐应助萝卜采纳,获得10
32秒前
牛奶煮萝莉完成签到 ,获得积分10
32秒前
淡淡的晓蓝完成签到,获得积分10
32秒前
keen发布了新的文献求助10
32秒前
坦率鬼卞发布了新的文献求助10
33秒前
研友_VZG7GZ应助庸人自扰采纳,获得10
33秒前
zxcvvbnm完成签到 ,获得积分10
33秒前
坦率大米完成签到,获得积分10
34秒前
高分求助中
Ophthalmic Equipment Market by Devices(surgical: vitreorentinal,IOLs,OVDs,contact lens,RGP lens,backflush,diagnostic&monitoring:OCT,actorefractor,keratometer,tonometer,ophthalmoscpe,OVD), End User,Buying Criteria-Global Forecast to2029 2000
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 588
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3962550
求助须知:如何正确求助?哪些是违规求助? 3508565
关于积分的说明 11141672
捐赠科研通 3241287
什么是DOI,文献DOI怎么找? 1791495
邀请新用户注册赠送积分活动 872888
科研通“疑难数据库(出版商)”最低求助积分说明 803474