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.
Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. doi: 10.1093/rheumatology/kex443.
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.
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.
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).
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.
ClinicalTrials.gov (http://www.clinicaltrials.gov) NCT01941940, NCT01941095, NCT01951170, NCT01987479, NCT01988012, NCT01995201, NCT02001987, NCT02011334, NCT02031471, NCT02046603 and NCT02046616.
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。
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。
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）。
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。
ClinicalTrials.gov（http://www.clinicaltrials.gov）NCT01941940、NCT01941095、NCT01951170、NCT01987479、NCT01988012、NCT01995201、NCT02001987、NCT02011334、NCT02031471、NCT02046603 和 NCT02046616。
