皮下注射托珠单抗治疗类风湿关节炎：在 22 个国家开展的共同框架 4 期研究计划 TOZURA 的研究结果。
Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries.
机构信息
CREATE Centre, Division of Infection and Immunity, Cardiff University, Cardiff, UK.
Division of Rheumatology, University of Pavia and IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
出版信息
Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. doi: 10.1093/rheumatology/kex443.
OBJECTIVES
The aim of this pooled analysis of the TOZURA study programme was to evaluate the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) in patients with moderate to severe RA who had an inadequate response to csDMARD or anti-TNF agent therapy or who were MTX naïve.
METHODS
TOZURA is a multinational, open-label, single-arm, common-framework, phase 4 study programme (11 protocols, 22 countries). Patients received TCZ-SC 162 mg each week for ⩾24 weeks, administered at the investigator's discretion, as monotherapy or in combination with a csDMARD. Efficacy, safety and immunogenicity were evaluated; propensity score-based matching was used for between-group comparisons.
RESULTS
Of 1804 patients, 353 (19.6%) received monotherapy and 1451 (80.4%) received combination therapy. The 28-joint DAS using ESR (DAS28-ESR) in both groups decreased significantly from baseline to week 24 (mean change: monotherapy -3.40, combination therapy -3.46), with no significant difference between groups (P = 0.46). The proportion of patients who achieved DAS28-ESR or Clinical Disease Activity Index remission or ACR 20/50/70/90 responses was similar between groups. Overall, 13.9% of patients withdrew-6.2% for safety reasons and 1.6% for insufficient therapeutic response; 5.8% of patients experienced one or more serious adverse events [14.6/100 patient-years (PY)]; six deaths occurred (0.64/100 PY).
CONCLUSION
In a common framework of 11 studies in 22 countries, this phase 4 study programme confirmed TCZ-SC's known efficacy and safety profile with comparable effects as monotherapy and in combination with csDMARDs.
TRIAL REGISTRATION
ClinicalTrials.gov (http://www.clinicaltrials.gov) NCT01941940, NCT01941095, NCT01951170, NCT01987479, NCT01988012, NCT01995201, NCT02001987, NCT02011334, NCT02031471, NCT02046603 and NCT02046616.
目的
TOZURA 研究计划的这一汇总分析旨在评估皮下注射托珠单抗（TCZ-SC）作为单药治疗或与传统合成 DMARD（csDMARD）联合治疗对 csDMARD 或抗 TNF 治疗反应不足或 MTX 初治的中度至重度 RA 患者的疗效和安全性。
方法
TOZURA 是一项多中心、开放性、单臂、通用框架、4 期研究计划（11 项方案，22 个国家）。患者每周接受 TCZ-SC 162mg，至少 24 周，由研究者自行决定，可作为单药治疗或与 csDMARD 联合治疗。评估疗效、安全性和免疫原性；采用倾向评分匹配进行组间比较。
结果
在 1804 例患者中，353 例（19.6%）接受单药治疗，1451 例（80.4%）接受联合治疗。两组 28 关节疾病活动度评分（DAS28-ESR）均较基线显著下降（单药组：-3.40，联合治疗组：-3.46），两组间无显著差异（P=0.46）。两组达到 DAS28-ESR 或临床疾病活动指数缓解或 ACR 20/50/70/90 反应的患者比例相似。总体而言，13.9%的患者因安全性原因（6.2%）或治疗反应不足（1.6%）而停药；5.8%的患者发生 1 次或多次严重不良事件（14.6/100 患者年）；6 例死亡（0.64/100 患者年）。
结论
在 22 个国家的 11 项研究的通用框架中，该 4 期研究计划证实了 TCZ-SC 的已知疗效和安全性，其疗效与单药治疗和与 csDMARD 联合治疗相当。
试验注册
ClinicalTrials.gov（http://www.clinicaltrials.gov）NCT01941940、NCT01941095、NCT01951170、NCT01987479、NCT01988012、NCT01995201、NCT02001987、NCT02011334、NCT02031471、NCT02046603 和 NCT02046616。
Zotero 插件