Kivitz Alan, Wallace Thomas, Olech Ewa, Borofsky Michael, Devenport Jenny, Pei Jinglan, Michalska Margaret
Altoona Arthritis and Osteoporosis Center, 175 Meadowbrook Lane, PO Box 909, Duncansville, PA, USA.
Genentech Inc., South San Francisco, CA, USA.
Rheumatol Ther. 2016 Dec;3(2):291-304. doi: 10.1007/s40744-016-0043-1. Epub 2016 Sep 24.
To assess the long-term safety and efficacy of subcutaneous tocilizumab (TCZ-SC) in US patients with rheumatoid arthritis (RA) who rolled over from the two global phase 3 studies, SUMMACTA (NCT01194414) and BREVACTA (NCT1232569), into this open-label, single-arm, phase 3b study.
Patients continued to receive TCZ-SC 162 mg weekly or every other week or switched from intravenous TCZ to TCZ-SC 162 mg qw for up to 84 weeks. The primary endpoint was the proportion of patients with serious adverse events (SAEs). Secondary endpoints included clinical efficacy, laboratory abnormalities, and immunogenicity.
Of the 217 patients treated, 76.5% were female, and the mean age was 58.4 years. A total of 23 patients (10.6%) had ≥1 SAE. The most common SAEs were infections (3.7%). Alanine aminotransferase elevations (38.2%) were not associated with hepatic injury. Grade 3/4 neutropenia (3%) was transient and not associated with serious infections. Immunogenicity was low (<1%) and not associated with SAEs. No anaphylaxis or deaths occurred. Thirteen patients (6.0%) withdrew due to safety reasons. Mean Clinical Disease Activity Index and Disease Activity Score in 28 joints remained stable throughout the trial.
The long-term safety of TCZ-SC during the long-term extension period was consistent with the safety profiles from SUMMACTA and BREVACTA, with no new safety signals. Efficacy improvements observed from baseline remained stable over time. These results demonstrated the durability of the safety and efficacy responses, and low immunogenicity, with long-term exposure to TCZ-SC in patients with RA.
F. Hoffmann-La Roche, Ltd.
ClinicalTrials.gov identifier, NCT01662063.
为评估皮下注射托珠单抗（TCZ-SC）在美国类风湿关节炎（RA）患者中的长期安全性和有效性，这些患者来自两项全球3期研究SUMMACTA（NCT01194414）和BREVACTA（NCT1232569），并转入这项开放标签、单臂3b期研究。
患者继续每周或每两周接受162mg皮下注射托珠单抗，或从静脉注射托珠单抗转换为每周162mg皮下注射托珠单抗，最长持续84周。主要终点是发生严重不良事件（SAE）的患者比例。次要终点包括临床疗效、实验室异常和免疫原性。
在接受治疗的217例患者中，76.5%为女性，平均年龄为58.4岁。共有23例患者（10.6%）发生≥1次SAE。最常见的SAE是感染（3.7%）。丙氨酸氨基转移酶升高（38.2%）与肝损伤无关。3/4级中性粒细胞减少（3%）是短暂的，与严重感染无关。免疫原性较低（<1%），且与SAE无关。未发生过敏反应或死亡。13例患者（6.0%）因安全原因退出。在整个试验过程中，平均临床疾病活动指数和28个关节的疾病活动评分保持稳定。
在长期延长期内，皮下注射托珠单抗的长期安全性与SUMMACTA和BREVACTA的安全性概况一致，未出现新 的安全信号。从基线观察到的疗效改善随时间保持稳定。这些结果表明，类风湿关节炎患者长期使用皮下注射托珠单抗时，安全性和疗效反应具有持久性，且免疫原性较低。
F. Hoffmann-La Roche, Ltd.
ClinicalTrials.gov标识符，NCT01662063。
