Shimizu Toshimasa, Kawashiri Shin-Ya, Sato Shuntaro, Morimoto Shimpei, Minoda Shuri, Kawazoe Yurika, Kuroda Shohei, Tashiro Shigeki, Sumiyoshi Remi, Hosogaya Naoki, Yamamoto Hiroshi, Kawakami Atsushi
Clinical Research Center, Nagasaki University Hospital.
Departments of Immunology and Rheumatology.
Medicine (Baltimore). 2020 Aug 7;99(32):e21480. doi: 10.1097/MD.0000000000021480.
The introduction of biological disease-modifying anti-rheumatic drugs into clinical practice has dramatically improved the clinical outcomes of individuals with rheumatoid arthritis (RA). We are conducting the IFX-SIRIUS STUDY I that evaluates whether switching from originator infliximab (IFX) to its biosimilar, CT-P13, is not inferior in maintaining nonclinical relapse to continue treatment with originator IFX in patients with RA achieving clinical remission. It is the next great issue whether disease activity can be maintained in good condition after discontinuation of CT-P13 because no evidence is available regarding the clinical value of discontinuing biosimilars in patients with RA. Thus, we will evaluate whether a condition without clinical relapse will be maintained after discontinuation of CT-P13 in patients with RA, achieving clinical remission or low disease activity during the IFX-SIRIUS STUDY I.
METHODS/DESIGN: This study is an interventional, multicenter, open-label, single-arm clinical trial with a 48-week follow-up. Patients with RA who are treated with CT-P13 and sustained nonclinical relapse during the IFX-SIRIUS STUDY I will be included. Patients will discontinue CT-P13 after the study period of the IFX-SIRIUS STUDY I. We will evaluate disease activity by clinical disease activity indices and musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who do not have clinical relapse during the study period. Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of multiple biomarkers, such as cytokines and chemokines. In addition, if a clinical relapse occurs in patients after the discontinuation of CT-P13, we will evaluate the effectiveness and safety of restarting CT-P13.
The study results are expected to show the clinical benefit of the discontinuation of CT-P13 and effectiveness and safety of restarting CT-P13 after clinical relapse. The strength of this study is to prospectively evaluate the therapeutic effectiveness by not only clinical disease activity indices but also standardized MSUS findings in multiple centers. We will explore whether parameters at baseline can predict a nonclinical relapse after the discontinuation of CT-P13 by integrating multilateral assessments, that is, patient's characteristics, clinical disease activity indices, MSUS findings, and serum biomarkers.
This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on April 20, 2020 as jRCTs071200007.
生物性改善病情抗风湿药引入临床实践后，类风湿关节炎（RA）患者的临床结局得到显著改善。我们正在开展IFX-SIRIUS研究I，以评估在达到临床缓解的RA患者中，从原研英夫利昔单抗（IFX）转换为其生物类似药CT-P13在维持无临床复发方面是否不劣于继续使用原研IFX治疗。由于尚无关于RA患者停用生物类似药临床价值的证据，停用CT-P13后能否维持良好的疾病活动状态成为下一个重大问题。因此，我们将评估在IFX-SIRIUS研究I期间达到临床缓解或低疾病活动度的RA患者停用CT-P13后是否能维持无临床复发状态。
方法/设计：本研究为一项干预性、多中心、开放标签、单臂临床试验，随访48周。纳入在IFX-SIRIUS研究I期间接受CT-P13治疗且持续无临床复发的RA患者。患者将在IFX-SIRIUS研究I的研究期结束后停用CT-P13。我们将通过临床疾病活动指数和肌肉骨骼超声（MSUS）评估疾病活动度。主要终点是研究期间无临床复发的患者比例。重要的次要终点是MSUS评分相对于基线的变化。我们还将综合分析多种生物标志物的血清水平，如细胞因子和趋化因子。此外，如果患者在停用CT-P13后发生临床复发，我们将评估重新使用CT-P13的有效性和安全性。
研究结果有望显示停用CT-P13的临床益处以及临床复发后重新使用CT-P13的有效性和安全性。本研究的优势在于不仅通过临床疾病活动指数，还通过多中心标准化的MSUS检查结果前瞻性评估治疗效果。我们将通过整合多方面评估，即患者特征、临床疾病活动指数、MSUS检查结果和血清生物标志物，探索基线参数能否预测停用CT-P13后的无临床复发情况。
本研究于2020年4月20日在日本临床试验注册中心（https://jrct.niph.go.jp）注册，注册号为jRCTs071200007。
