Division of Rheumatology, Medical University of Vienna, Wien, Austria
Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA.
RMD Open. 2021 Jan;7(1). doi: 10.1136/rmdopen-2020-001465.
Interleukin (IL)-6 is a pleiotropic cytokine involved in the pathophysiology of rheumatoid arthritis (RA). Sirukumab is a human monoclonal antibody that binds to IL-6 with high affinity and specificity.
This long-term extension (LTE) study of the SIRROUND-D and SIRROUND-T studies assessed long-term safety and efficacy of sirukumab in adults with moderate-to-severe RA refractory to conventional disease-modifying antirheumatic drug therapy or antitumor necrosis factor agents. Patients received sirukumab 100 mg subcutaneously (SC) every 2 weeks (q2w) or sirukumab 50 mg SC every 4 weeks (q4w).
1820 patients enrolled in the LTE; median exposure was 2.34 and 2.07 years in sirukumab 50 mg q4w and 100 mg q2w groups, respectively. Adverse events (AEs) occurred in similar proportions between groups, with the exception of major adverse cardiovascular events (MACE), which were more common in the 50 mg q4w versus 100 mg q2w group (2.2% vs 1.0%), and injection-site reactions, more common in the 100 mg q2w group versus 50 mg q4w group (7.5% vs 3.7%). The most common serious AEs were infections (10% of the patients); 32 (1.8%) patients died during the study (primarily from serious infection and MACE). Malignancies were reported in 24 (1.3%) patients. Gastrointestinal perforations, hepatobiliary abnormalities and changes in laboratory parameters were rare. Reductions in RA signs and symptoms and improvements in physical function were maintained throughout the LTE.
The safety profile of sirukumab in the LTE remained consistent with that reported in SIRROUND-D and SIRROUND-T and efficacy was maintained.
NCT01856309.
白细胞介素（IL）-6 是一种多效细胞因子，参与类风湿关节炎（RA）的病理生理学过程。Sirukumab 是一种与人源单克隆抗体，具有高亲和力和特异性结合 IL-6。
本项 SIRROUND-D 和 SIRROUND-T 研究的长期扩展（LTE）研究评估了 sirukumab 在对常规疾病修饰抗风湿药物治疗或抗肿瘤坏死因子药物难治的中重度 RA 成人患者中的长期安全性和疗效。患者接受 sirukumab 100mg 皮下（SC）每 2 周（q2w）或 sirukumab 50mg SC 每 4 周（q4w）治疗。
1820 名患者入组 LTE；sirukumab 50mg q4w 和 100mg q2w 组的中位暴露时间分别为 2.34 年和 2.07 年。两组间不良反应（AE）的发生率相似，除重大心血管不良事件（MACE）外，50mg q4w 组发生率高于 100mg q2w 组（2.2% vs. 1.0%），注射部位反应在 100mg q2w 组更常见（7.5% vs. 3.7%）。最常见的严重 AE 为感染（10%的患者）；研究期间有 32 名（1.8%）患者死亡（主要死于严重感染和 MACE）。有 24 名（1.3%）患者报告发生恶性肿瘤。胃肠道穿孔、肝胆异常和实验室参数改变少见。整个 LTE 期间，RA 症状和体征的改善和身体功能的提高得以维持。
sirukumab 在 LTE 的安全性与 SIRROUND-D 和 SIRROUND-T 研究报告的安全性一致，疗效得以维持。
NCT01856309。
