sirukumab 在对柳氮磺胺吡啶或甲氨蝶呤难治的类风湿关节炎中的应用：一项日本患者的随机 3 期安全性和疗效研究。
Sirukumab in rheumatoid arthritis refractory to sulfasalazine or methotrexate: a randomized phase 3 safety and efficacy study in Japanese patients.
机构信息
Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
出版信息
Arthritis Res Ther. 2018 Mar 7;20(1):42. doi: 10.1186/s13075-018-1536-9.
BACKGROUND
Sirukumab, a high-affinity human monoclonal antibody that selectively binds to interleukin-6, has demonstrated efficacy in the treatment of rheumatoid arthritis (RA) in global phase 1 and phase 2 studies. The present study evaluated the safety and efficacy of sirukumab, as monotherapy in Japanese patients with RA refractory to methotrexate or sulfasalazine.
METHODS
In this phase 3, double-blind study, 122 patients (age ≥ 20 years) were randomized (1:1, 61 patients in each arm) to sirukumab administered subcutaneously: 50 mg once every 4 weeks (q4w) or 100 mg once every 2 weeks (q2w) through 52 weeks. Disease-modifying anti-rheumatic drugs were allowed after 24 weeks. Safety was assessed and efficacy was evaluated using American College of Rheumatology (ACR) responses, Disease Activity Score C-reactive protein (DAS28-CRP) and Health Assessment Questionnaire-Disability Index (HAQ-DI).
RESULTS
Amongst the 122 randomized patients, 99 (81.1%) patients completed the study. Adverse events (AEs) were reported in 114/122 (93.4%) patients and serious AEs were reported in 9/122 (7.4%) patients. No deaths, major cardiovascular AEs, serious gastrointestinal perforations or tuberculosis cases were reported during this study period. Grade 3 hematologic abnormalities (neutropenia and leukopenia) were reported in seven patients and no grade 4 abnormalities were observed. ACR20 responses were observed within 2 weeks, achieved in 47/61 (77.0%, 50 mg q4w) patients and 44/61 (72.1%, 100 mg q2w) patients at week 16 and maintained through week 52. ACR50/70, DAS28-CRP and HAQ-DI responses were also maintained through week 52 in both groups.
CONCLUSIONS
Safety findings were comparable between the two treatment groups. The 52-week administration of sirukumab at 50 mg q4w and 100 mg q2w was generally tolerable and with measurable efficacy in Japanese patients with RA refractory to methotrexate and sulfasalazine.
TRIAL REGISTRATION
NCT01689532 . Registered 18 September 2012.
背景
西鲁单抗是一种高亲和力的人源单克隆抗体，能选择性地与白细胞介素-6 结合，在全球的 1 期和 2 期研究中已显示出对类风湿关节炎（RA）的疗效。本研究评估了西鲁单抗在对甲氨蝶呤或柳氮磺胺吡啶耐药的日本 RA 患者中的安全性和疗效，该药作为单药治疗。
方法
在这项 3 期、双盲研究中，122 例（年龄≥20 岁）患者按 1:1 随机分为两组，分别接受皮下注射西鲁单抗：50mg 每 4 周（q4w）一次（61 例）或 100mg 每 2 周（q2w）一次（61 例），共 52 周。24 周后允许使用改善病情的抗风湿药物。采用美国风湿病学会（ACR）应答、疾病活动评分 C 反应蛋白（DAS28-CRP）和健康评估问卷残疾指数（HAQ-DI）评估安全性和疗效。
结果
在 122 例随机患者中，99 例（81.1%）完成了研究。122 例患者中有 114 例（93.4%）报告了不良事件（AE），9 例（7.4%）报告了严重 AE。研究期间无死亡、重大心血管不良事件、严重胃肠道穿孔或结核病病例。7 例患者出现 3 级血液学异常（中性粒细胞减少和白细胞减少），未观察到 4 级异常。在第 2 周时观察到 ACR20 应答，在第 16 周时，50mg q4w 组有 47/61（77.0%）例患者和 100mg q2w 组有 44/61（72.1%）例患者达到应答，在第 52 周时仍保持应答。两组在第 52 周时 ACR50/70、DAS28-CRP 和 HAQ-DI 应答也得以维持。
结论
两组的安全性发现相当。在对甲氨蝶呤和柳氮磺胺吡啶耐药的日本 RA 患者中，52 周给予西鲁单抗 50mg q4w 和 100mg q2w 的治疗是可耐受的，且具有可衡量的疗效。
试验注册
NCT01689532。注册日期 2012 年 9 月 18 日。
Zotero 插件