Lillegraven Siri, Paulshus Sundlisæter Nina, Aga Anna-Birgitte, Sexton Joseph, Olsen Inge C, Fremstad Hallvard, Spada Cristina, Madland Tor Magne, Høili Christian A, Bakland Gunnstein, Lexberg Åse, Hansen Inger Johanne Widding, Hansen Inger Myrnes, Haukeland Hilde, Ljoså Maud-Kristine Aga, Moholt Ellen, Uhlig Till, Solomon Daniel H, van der Heijde Désirée, Kvien Tore K, Haavardsholm Espen A
Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway.
Clinical Trial Unit, Oslo University Hospital, Oslo, Norway.
JAMA. 2021 May 4;325(17):1755-1764. doi: 10.1001/jama.2021.4542.
Sustained remission has become an achievable goal for patients with rheumatoid arthritis (RA) receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but how to best treat patients in clinical remission remains unclear.
To assess the effect of tapering of csDMARDs, compared with continuing csDMARDs without tapering, on the risk of flares in patients with RA in sustained remission.
DESIGN, SETTING, AND PARTICIPANTS: ARCTIC REWIND was a multicenter, randomized, parallel, open-label noninferiority study conducted in 10 Norwegian hospital-based rheumatology practices. A total of 160 patients with RA in remission for 12 months who were receiving stable csDMARD therapy were enrolled between June 2013 and June 2018, and the final visit occurred in June 2019.
Patients were randomly assigned to half-dose csDMARDs (n = 80) or stable-dose csDMARDs (n = 80).
The primary end point was the proportion of patients with a disease flare between baseline and the 12-month follow-up, defined as a combination of Disease Activity Score (DAS) greater than 1.6 (threshold for RA remission), an increase in DAS score of 0.6 units or more, and at least 2 swollen joints. A disease flare could also be recorded if both the patient and investigator agreed that a clinically significant flare had occurred. A risk difference of 20% was defined as the noninferiority margin.
Of 160 enrolled patients (mean [SD] age, 55.1 [11.9] years; 66% female), 156 received the allocated therapy, of which 155 without any major protocol violations were included in the primary analysis population (77 receiving half-dose and 78 receiving stable-dose csDMARDs). Flare occurred in 19 patients (25%) in the half-dose csDMARD group compared with 5 (6%) in the stable-dose csDMARD group (risk difference, 18% [95% CI, 7%-29%]). Adverse events occurred in 34 patients (44%) in the half-dose group and 42 (54%) in the stable-dose group, none leading to study discontinuation. No deaths occurred.
Among patients with RA in remission taking csDMARD therapy, treatment with half-dose vs stable-dose csDMARDs did not demonstrate noninferiority for the percentage of patients with disease flares over 12 months, and there were significantly fewer flares in the stable-dose group. These findings do not support treatment with half-dose therapy.
ClinicalTrials.gov Identifier: NCT01881308.
对于接受传统合成抗风湿药物（csDMARDs）治疗的类风湿关节炎（RA）患者而言，持续缓解已成为一个可实现的目标，但如何最佳地治疗处于临床缓解期的患者仍不明确。
评估与不减量持续使用csDMARDs相比，csDMARDs减量对处于持续缓解期的RA患者病情复发风险的影响。
设计、地点和参与者：ARCTIC REWIND是一项在挪威10家医院的风湿病科开展的多中心、随机、平行、开放标签的非劣效性研究。2013年6月至2018年6月期间，共纳入160例接受稳定csDMARD治疗且病情缓解12个月的RA患者，最后一次访视于2019年6月进行。
患者被随机分配至半量csDMARDs组（n = 80）或稳定剂量csDMARDs组（n = 80）。
主要终点是基线至12个月随访期间病情复发的患者比例，定义为疾病活动评分（DAS）大于1.6（RA缓解阈值）、DAS评分增加0.6个单位或更多以及至少2个关节肿胀的组合。如果患者和研究者均认为发生了具有临床意义的病情复发，也可记录为病情复发。将20%的风险差异定义为非劣效界值。
160例纳入患者（平均[标准差]年龄为55.1[11.9]岁；66%为女性）中，156例接受了分配的治疗，其中155例未违反任何主要方案被纳入主要分析人群（77例接受半量csDMARDs，78例接受稳定剂量csDMARDs）。半量csDMARDs组有19例患者（25%）病情复发，而稳定剂量csDMARDs组有5例（6%）（风险差异为18%[95%置信区间，7%-29%]）。半量组34例患者（44%）发生不良事件，稳定剂量组42例（54%）发生不良事件，均未导致研究中止。无死亡病例。
在接受csDMARD治疗且病情缓解的RA患者中，半量与稳定剂量csDMARDs治疗在12个月内病情复发患者百分比方面未显示非劣效性，且稳定剂量组病情复发明显较少。这些发现不支持半量治疗。
ClinicalTrials.gov标识符：NCT01881308。
