Interdisciplinary Center of Clinical Research, University of Münster, Munster, Germany.
Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany.
Ann Rheum Dis. 2022 Jul;81(7):990-997. doi: 10.1136/annrheumdis-2021-222029. Epub 2022 Mar 8.
To investigate the ability of high-sensitivity C-reactive protein (hsCRP) and S100A12 to serve as predictive biomarkers of successful drug withdrawal in children with clinical remission of juvenile idiopathic arthritis (JIA).
This multicentre trial (PREVENT-JIA) enrolled 119 patients with JIA in clinical remission, and 100 patients reached the intervention phase in which the decision whether to continue or stop treatment was based on S100A12 and hsCRP levels. Patients were monitored for 12 months after stopping medication for flares of disease. Results were compared with withdrawal of therapy without biomarker-based stratification in patients from the German Biologika in der Kinderrheumatologie (BiKeR) pharmacovigilance registry.
In the PREVENT-JIA group, 49 patients had a flare, and 45% of patients stopping medication showed flares within the following 12 months. All patients (n=8) continuing therapy due to permanently elevated S100A12/hsCRP at more than one visit flared during the observation phase. In the BiKeR control group, the total flare rate was 62%, with 60% flaring after stopping medication. The primary outcome, time from therapy withdrawal to first flare (cumulative flare rate after therapy withdrawal), showed a significant difference in favour of the PREVENT-JIA group (p=0.046; HR 0.62, 95% CI 0.38 to 0.99). As additional finding, patients in the PREVENT-JIA trial stopped therapy significantly earlier.
Biomarker-guided strategies of therapy withdrawal are feasible in clinical practice. This study demonstrates that using predictive markers of subclinical inflammation is a promising tool in the decision-making process of therapy withdrawal, which translates into direct benefit for patients.
ISRCTN69963079.
探讨高敏 C 反应蛋白（hsCRP）和 S100A12 在儿童幼年特发性关节炎（JIA）临床缓解期成功停药中的预测生物标志物作用。
这项多中心试验（PREVENT-JIA）纳入了 119 例临床缓解的 JIA 患儿，其中 100 例患儿进入干预阶段，是否继续或停止治疗取决于 S100A12 和 hsCRP 水平。停止药物治疗后，患者监测 12 个月以观察疾病复发情况。结果与德国儿童风湿病生物制剂监测登记处（BiKeR）无生物标志物分层的停药治疗患者进行比较。
在 PREVENT-JIA 组中，有 49 例患者出现复发，45%的停药患者在接下来的 12 个月内出现复发。所有因 S100A12/hsCRP 持续升高（就诊时至少一次高于正常）而持续治疗的患者（n=8）在观察阶段均出现复发。在 BiKeR 对照组中，总复发率为 62%，停药后 60%的患者复发。主要结局是从停药到首次复发的时间（停药后复发累积率），PREVENT-JIA 组有显著差异（p=0.046；HR 0.62，95%CI 0.38 至 0.99）。作为附加发现，PREVENT-JIA 试验中的患者更早停止了治疗。
基于生物标志物的停药策略在临床实践中是可行的。本研究表明，使用亚临床炎症的预测标志物是停药决策过程中的一种有前途的工具，可为患者带来直接获益。
ISRCTN69963079。
