IRCCS Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia, Pediatric Rheumatology Unit, Genoa, Italy.
IRCCS Istituto Giannina Gaslini, Direzione Scientifica, Genoa, Italy.
Pediatr Rheumatol Online J. 2022 Sep 7;20(1):80. doi: 10.1186/s12969-022-00739-x.
Although a satisfactory disease control is nowadays achievable in most patients with JIA, a substantial proportion of them still do not respond adequately or reach long-term drug-free remission. According to current recommendations, treatment should be escalated in subsequent steps. A different approach is based on the assumption that the initial start of an aggressive therapy may take advantage of the "window of opportunity" and could alter the biology of the disease, leading to an improvement of long-term outcomes, including the prevention of cumulative joint damage.
This randomised clinical trial aims to compare the effectiveness of a conventional therapeutic regimen, based on treatment escalation and driven by the treat-to-target approach, with that of an early aggressive intervention based on the initial start of a combination of conventional and biological DMARDs.
JIA patients with oligoarthritis or RF negative polyarthritis aged more than 2 years and with less than 4 months of disease course will be included in the study. Children will be randomised into two arms: patients in Step-up arm with less severe oligoarthritis will undergo an intra-articular corticosteroid injection (IACI) in all affected joints; patients with polyarthritis or severe oligoarthritis will receive IACI and methotrexate. Subsequent treatment will follow a standardised protocol based on the patients' level of disease activity measured with the JADAS, according to a treat-to-target strategy. Patients in Step-down arm will receive a 6-month early combined treatment (methotrexate plus IACI for less severe oligoarthritis, methotrexate plus etanercept for severe oligoarthritis and polyarthritis). The primary endpoint is the frequency of achievement of the status of clinical remission (i.e. persistence of inactive disease for at least 6 months) at the 12-month visit. Safety events, physician-centred measures and parent/patient-reported outcomes will be collected through the Paediatric Rheumatology International Trials Organisation on line database.
The STARS trial aims to provide important evidence supporting the first-line treatment choices in the care of children with oligoarticular and polyarticular JIA. If the superiority of an early aggressive therapy will be demonstrated, this will demand further studies on the biological definition of the window of opportunity for JIA.
The Trial is registered on the ClinicalTrials.gov registry (NCT03728478) on the 31st October 2018 and EU Clinical Trials Register on the 14th May 2018 (EudraCT Number: 2018-001931-27).
尽管目前大多数幼年特发性关节炎（JIA）患者可以实现满意的疾病控制，但仍有相当一部分患者不能充分缓解或达到长期无药物缓解。根据目前的建议，应在后续步骤中逐步升级治疗。另一种方法基于这样的假设，即初始开始强化治疗可能会利用“机会之窗”，并改变疾病的生物学特性，从而改善长期结局，包括预防累积关节损伤。
本随机临床试验旨在比较基于治疗升级和以达标为导向的传统治疗方案与基于初始使用传统和生物 DMARDs 联合治疗的早期强化干预的有效性。
将纳入年龄大于 2 岁且病程少于 4 个月的少关节炎或 RF 阴性多关节炎 JIA 患儿。患儿将被随机分为两组：少关节炎患者关节病变较轻，接受关节内皮质激素注射（IACI）；多关节炎或严重少关节炎患者接受 IACI 和甲氨蝶呤治疗。后续治疗将根据患儿疾病活动度的 JADAS 评分，根据达标策略，遵循标准化方案。接受标准治疗的患者为接受早期联合治疗（轻少关节炎患者用甲氨蝶呤加 IACI，严重少关节炎和多关节炎患者用甲氨蝶呤加依那西普）。主要终点是在 12 个月时达到临床缓解状态的频率（即至少 6 个月无活动疾病）。安全性事件、医生中心评估指标和家长/患儿报告的结果将通过儿科风湿病国际试验组织在线数据库收集。
STARS 试验旨在提供支持儿童少关节炎和多关节炎 JIA 治疗一线选择的重要证据。如果早期强化治疗的优越性得到证实，这将需要进一步研究 JIA 机会之窗的生物学定义。
该试验于 2018 年 10 月 31 日在 ClinicalTrials.gov 注册（NCT03728478），并于 2018 年 5 月 14 日在欧盟临床试验注册处（EudraCT 编号：2018-001931-27）注册。
