Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis with up to 7 years' follow-up.
Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis with up to 7 years' follow-up.
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DOI：
10.1093/rheumatology/kez265
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发表时间：
2020-02-01
期刊：
影响因子：
--
通讯作者：
Burmester GR
中科院分区：
文献类型：
--
作者：
Fleischmann R;Genovese MC;Lin Y;St John G;van der Heijde D;Wang S;Gomez-Reino JJ;Maldonado-Cocco JA;Stanislav M;Kivitz AJ;Burmester GR
Sarilumab是一种人单克隆抗体，可阻断IL-6与膜结合和可溶性IL-6受体-α的结合。我们从8项临床试验及其开放标签扩展中评估了sarilumab在患者中的长期安全性。数据来自于接受至少一剂sarilumab联合常规合成疾病改善抗风湿药物（csDMARDs；联合组）或单药治疗（单药治疗组）的类风湿性关节炎患者。评估治疗中出现的不良事件（ae）、ae和特殊关注的实验室值。沙伐单抗联合csDMARDs治疗2887例，沙伐单抗单药治疗471例，平均暴露时间分别为2.8年和1.7年，最大暴露时间分别为7.3年和3.5年，AE累计观察时间分别为8188和812患者年。在联合治疗组和单一治疗组中，每100患者年的发病率分别为：严重不良事件9.4和6.7，严重感染3.7和1.0，带状疱疹0.6和0.5（无播散性病例），胃肠道穿孔0.1和0，主要不良心血管事件0.5和0.2，恶性肿瘤0.7和0.6。绝对中性粒细胞计数<1000细胞/mm3分别记录在13%和15%的患者中。中性粒细胞减少与感染或严重感染的风险增加无关。6个月的间隔分析显示，随着时间的推移，没有任何AE发生率增加的迹象。sarilumab的长期安全性，无论是与csDMARDs联合使用还是单独使用，都保持稳定，并与预期的抑制il - 6信号传导的分子特征一致。
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.
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影响因子：
27.4
作者：
Cohen SB;Tanaka Y;Mariette X;Curtis JR;Lee EB;Nash P;Winthrop KL;Charles-Schoeman C;Thirunavukkarasu K;DeMasi R;Geier J;Kwok K;Wang L;Riese R;Wollenhaupt J
通讯作者：
Wollenhaupt J
影响因子：
6.2
作者：
Fleischmann R;Wollenhaupt J;Takiya L;Maniccia A;Kwok K;Wang L;van Vollenhoven RF
通讯作者：
van Vollenhoven RF
影响因子：
3.9
作者：
Genovese, Mark C.;Rubbert-Roth, Andrea;Van Vollenhoven, Ronald
通讯作者：
Van Vollenhoven, Ronald
影响因子：
4.2
作者：
Scott, Ian C.;Hider, Samantha L.;Scott, David L.
通讯作者：
Scott, David L.
影响因子：
4.7
作者：
Curtis, Jeffrey R.;Lanas, Angel;John, Ani;Johnson, David A.;Schulman, Kathy L.
通讯作者：
Schulman, Kathy L.