Fleischmann Roy, Genovese Mark C, Lin Yong, St John Gregory, van der Heijde Désirée, Wang Sheldon, Gomez-Reino Juan Jose, Maldonado-Cocco Jose Antonio, Stanislav Marina, Kivitz Alan J, Burmester Gerd R
Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, TX.
Division of Immunology and Rheumatology, Stanford University, Palo Alto, CA.
Rheumatology (Oxford). 2020 Feb 1;59(2):292-302. doi: 10.1093/rheumatology/kez265.
Sarilumab is a human monoclonal antibody that blocks IL-6 from binding to membrane-bound and soluble IL-6 receptor-α. We assessed the long-term safety of sarilumab in patients from eight clinical trials and their open-label extensions.
Data were pooled from patients with rheumatoid arthritis who received at least one dose of sarilumab in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; combination group) or as monotherapy (monotherapy group). Treatment-emergent adverse events (AEs) and AEs and laboratory values of special interest were assessed.
2887 patients received sarilumab in combination with csDMARDs and 471 patients received sarilumab monotherapy, with mean exposure of 2.8 years and 1.7 years, maximum exposure 7.3 and 3.5 years, and cumulative AE observation period of 8188 and 812 patient-years, respectively. Incidence rates per 100 patient-years in the combination and monotherapy groups, respectively, were 9.4 and 6.7 for serious AEs, 3.7 and 1.0 for serious infections, 0.6 and 0.5 for herpes zoster (no cases were disseminated), 0.1 and 0 for gastrointestinal perforations, 0.5 and 0.2 for major adverse cardiovascular events, and 0.7 and 0.6 for malignancy. Absolute neutrophil counts <1000 cells/mm3 were recorded in 13% and 15% of patients, respectively. Neutropenia was not associated with increased risk of infection or serious infection. Analysis by 6-month interval showed no signal for increased rate of any AE over time.
The long-term safety profile of sarilumab, either in combination with csDMARDs or as monotherapy, remained stable and consistent with the anticipated profile of a molecule that inhibits IL6 signalling.
萨瑞鲁单抗是一种人源单克隆抗体，可阻止白细胞介素-6（IL-6）与膜结合型和可溶性IL-6受体-α结合。我们评估了萨瑞鲁单抗在八项临床试验及其开放标签扩展研究患者中的长期安全性。
汇总类风湿关节炎患者的数据，这些患者接受了至少一剂萨瑞鲁单抗联合传统合成抗风湿药物（csDMARDs；联合治疗组）或作为单药治疗（单药治疗组）。评估治疗中出现的不良事件（AE）以及特别关注的AE和实验室检查值。
2887例患者接受萨瑞鲁单抗联合csDMARDs治疗，471例患者接受萨瑞鲁单抗单药治疗，平均暴露时间分别为2.8年和1.7年，最大暴露时间为7.3年和3.5年，累积AE观察期分别为8188和812患者年。联合治疗组和单药治疗组每100患者年的发生率分别为：严重AE为9.4和6.7，严重感染为3.7和1.0，带状疱疹为0.6和0.5（无播散性病例），胃肠道穿孔为0.1和0，主要不良心血管事件为0.5和0.2，恶性肿瘤为0.7和0.6。分别有13%和15%的患者记录到绝对中性粒细胞计数<1000个细胞/mm³。中性粒细胞减少与感染或严重感染风险增加无关。按6个月间隔分析显示，未发现任何AE发生率随时间增加的信号。
萨瑞鲁单抗联合csDMARDs或作为单药治疗的长期安全性概况保持稳定，与抑制IL-6信号传导分子的预期概况一致。
