German Rheumatism Research Centre, Leibniz Institute, 10117, Berlin, Germany.
Centre for Paediatric Rheumatology, Department of Paediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany.
Arthritis Res Ther. 2021 Apr 16;23(1):118. doi: 10.1186/s13075-021-02492-0.
To determine (i) correlates for etanercept (ETA) discontinuation after achieving an inactive disease and for the subsequent risk of flare and (ii) to analyze the effectiveness of ETA in the re-treatment after a disease flare.
Data from two ongoing prospective registries, BiKeR and JuMBO, were used for the analysis. Both registries provide individual trajectories of clinical data and outcomes from childhood to adulthood in juvenile idiopathic arthritis (JIA) patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) and conventional synthetic DMARDs (csDMARDs).
A total of 1724 patients were treated first with ETA treatment course (338 with second, 54 with third ETA course). Similar rates of discontinuation due to ineffectiveness and adverse events could be observed for the first (19.4%/6.2%), second (18.6%/5.9%), and third (14.8%/5.6%) ETA course. A total of 332 patients (+/-methotrexate, 19.3%) discontinued ETA after achieving remission with the first ETA course. Younger age (hazard ratio (HR) 1.08, p < 0.001), persistent oligoarthritis (HR 1.89, p = 0.004), and shorter duration between JIA onset and ETA start (HR 1.10, p < 0.001), as well as good response to therapy within the first 6 months of treatment (HR 1.11, p < 0.001) significantly correlated to discontinuation with inactive disease. Reoccurrence of active disease was reported for 77% of patients with mean time to flare of 12.1 months. We could not identify any factor correlating to flare risk. The majority of patients were re-treated with ETA (n = 117 of 161; 72.7%) after the flare. One in five patients (n = 23, 19.7%) discontinued ETA again after achieving an inactive disease and about 70% of the patients achieved an inactive disease 12 months after restarting ETA.
The study confirms the effectiveness of ETA even for re-treatment of patients with JIA. Our data highlight the association of an early bDMARD treatment with a higher rate of inactive disease indicating a window of opportunity.
确定(i)在达到疾病缓解后停用依那西普(ETA)的相关性,以及随后疾病复发的风险;(ii)分析 ETA 在疾病复发后的再治疗中的有效性。
本研究使用了两项正在进行的前瞻性登记研究(BiKeR 和 JuMBO)的数据。这两项登记研究均提供了儿童期至成年期幼年特发性关节炎(JIA)患者接受生物改善病情抗风湿药物(bDMARDs)和传统合成改善病情抗风湿药物(csDMARDs)治疗的临床数据和结果的个体轨迹。
共有 1724 名患者首先接受 ETA 治疗疗程(338 名接受第二次治疗,54 名接受第三次治疗)。第一次(19.4%/6.2%)、第二次(18.6%/5.9%)和第三次(14.8%/5.6%)ETA 治疗疗程因无效和不良反应而停药的比例相似。共有 332 名患者(+/-甲氨蝶呤,19.3%)在首次 ETA 疗程达到缓解后停用 ETA。年龄较小(风险比(HR)1.08,p<0.001)、持续性少关节炎(HR 1.89,p=0.004)、JIA 发病和 ETA 开始之间的时间较短(HR 1.10,p<0.001),以及治疗前 6 个月内治疗反应良好(HR 1.11,p<0.001)与疾病缓解后停药显著相关。77%的患者报告疾病复发,平均复发时间为 12.1 个月。我们未能确定任何与复发风险相关的因素。大多数患者(n=161;72.7%)在疾病复发后接受 ETA 再治疗。五分之一的患者(n=23,19.7%)在达到疾病缓解后再次停用 ETA,约 70%的患者在重新开始 ETA 治疗 12 个月后达到疾病缓解。
本研究证实了 ETA 的有效性,即使对于 JIA 患者的再治疗也是如此。我们的数据强调了早期 bDMARD 治疗与更高的疾病缓解率相关,表明存在机会窗口。