New York University Hospital for Joint Diseases, New York, USA.
Ann Rheum Dis. 2012 Feb;71(2):198-205. doi: 10.1136/ard.2010.148700. Epub 2011 Sep 26.
To evaluate efficacy of tocilizumab in US patients with moderate to severe active rheumatoid arthritis (RA) and inadequate clinical response to disease-modifying antirheumatic drugs (DMARD). Safety-related outcomes were also analysed.
The rapid onset and systemic efficacy study was a 24-week, randomised, double-blind trial. Patients were randomly assigned 2:1 to tocilizumab 8 mg/kg (n=412) or placebo (n=207) every 4 weeks while continuing background DMARD in both groups.
The primary efficacy endpoint, percentage of patients achieving ACR50 response at week 24, was higher with tocilizumab versus placebo (30.1% vs 11.2%; p<0.0001). Percentages of ACR20 and ACR50 responders were significantly higher with tocilizumab versus placebo as early as week 4 and continued to week 24; more patients in the tocilizumab versus placebo group also achieved ACR70 responses beginning at week 8 (p<0.01). Significant improvements associated with tocilizumab versus placebo were seen in routine assessment of patient index data responses, EULAR good response, DAS28 and percentages of patients achieving low disease activity and clinical remission (based on DAS28). A substudy examining early response to therapy showed improved patient global assessment of disease activity (p=0.005) and pain (p=0.01) and DAS28 (p=0.007) with tocilizumab versus placebo at day 7. Safety findings were consistent with the known tocilizumab safety profile; rates of serious infections (per 100 patient-years) were 7.87 (95% CI 4.30 to 13.2) and 1.20 (95% CI 0.03 to 6.66) in the tocilizumab and placebo groups, respectively.
This study demonstrated the efficacy of tocilizumab in improving measures of disease activity in patients with RA who failed to respond adequately to DMARD therapy. Rapid improvement in clinical outcomes was demonstrated in a substudy as early as week 1 as shown by DAS28 scores, patient measures and C-reactive protein. TRIAL REGISTRY NO: NCT00531817.
评估托珠单抗在美国中重度活动性类风湿关节炎（RA）患者中的疗效，这些患者对疾病修饰抗风湿药物（DMARD）治疗反应不足。还分析了与安全性相关的结果。
快速起始和系统疗效研究是一项为期 24 周、随机、双盲试验。患者被随机分配 2:1 接受托珠单抗 8mg/kg（n=412）或安慰剂（n=207），每 4 周一次，同时两组均继续使用背景 DMARD。
主要疗效终点为第 24 周时达到 ACR50 应答的患者比例，托珠单抗组高于安慰剂组（30.1% vs 11.2%；p<0.0001）。托珠单抗组的 ACR20 和 ACR50 应答者比例从第 4 周开始显著高于安慰剂组，并持续至第 24 周；托珠单抗组更多的患者也从第 8 周开始达到 ACR70 应答（p<0.01）。与安慰剂相比，托珠单抗治疗还显著改善了常规评估的患者指数数据应答、EULAR 良好应答、DAS28 以及达到低疾病活动度和临床缓解的患者比例（基于 DAS28）。一项探索早期治疗应答的亚研究显示，与安慰剂相比，托珠单抗组患者的疾病活动度（p=0.005）、疼痛（p=0.01）和 DAS28（p=0.007）的总体改善更显著。安全性发现与已知的托珠单抗安全性特征一致；托珠单抗组的严重感染发生率（每 100 患者-年）为 7.87（95%CI 4.30 至 13.2），安慰剂组为 1.20（95%CI 0.03 至 6.66）。
这项研究证明了托珠单抗在改善对 DMARD 治疗反应不足的 RA 患者疾病活动度方面的疗效。一项亚研究显示，在第 1 周时，DAS28 评分、患者指标和 C 反应蛋白就显示出了临床结局的快速改善。
NCT00531817。
