Longterm Safety and Efficacy of Tocilizumab in Patients with Rheumatoid Arthritis: A Cumulative Analysis of Up to 4.6 Years of Exposure
Longterm Safety and Efficacy of Tocilizumab in Patients with Rheumatoid Arthritis: A Cumulative Analysis of Up to 4.6 Years of Exposure
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DOI：
10.3899/jrheum.120687
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发表时间：
2013-06-01
影响因子：
3.9
通讯作者：
Van Vollenhoven, Ronald
中科院分区：
文献类型：
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作者：
Genovese, Mark C.;Rubbert-Roth, Andrea;Van Vollenhoven, Ronald
目标。评估tocilizumab （TCZ）治疗中重度类风湿关节炎（RA）患者的长期安全性和有效性。患者数据来自5项随机对照TCZ试验（n = 4211）、其开放标签扩展阶段（n = 3512）和一项药物相互作用研究（n = 23）。所有随机分配的患者，无论之前是否接受过RA治疗，均被分析。安全性指标包括不良事件（AE）、严重AE （SAE）、AE导致治疗中断、实验室检查和死亡的数量。疗效指标包括美国风湿病学会（ACR） 20/50/70反应，压痛关节计数（TJC），肿胀关节计数（SIC）， ACR核心组件，28个关节的低疾病活动性（LDA）或疾病活动性评分（DAS28）缓解。ACR/欧洲抗风湿病联盟（EULAR）疾病缓解是一项术后探索性分析。总观察时间为12293患者年（PY）。没有发现新的安全信号;AE和SAE感染最为常见。严重感染率为4.5/100 PY。以ACR20/50/70反应、TIC、SIC、ACR核心组成分以及LDA和DAS28缓解来衡量的临床疗效较基线的改善通常持续至少216周的随访。第216周ACR/EULAR疾病缓解率分别为16.5%（布尔值）和22.7%（指数）。迄今为止，TCZ在类风湿关节炎患者中的治疗研究已长达4.6年（240周）。我们的分析显示TCZ的长期安全性与之前的观察结果一致，没有新的安全信号，并且在大型临床试验项目中具有持久的疗效。
Objective. To assess the longterm safety and efficacy of tocilizumab (TCZ) in patients with moderate to severe rheumatoid arthritis (RA).Methods. Patient data were from 5 randomized controlled TCZ trials (n = 4211), their open-label extension phases (n = 3512), and a drug interaction study (n = 23). All randomly assigned patients, regardless of previous RA treatment, were analyzed. Measures of safety included number of adverse events (AE), serious AE (SAE), AE leading to treatment discontinuation, laboratory tests, and deaths. Efficacy measures included American College of Rheumatology (ACR) 20/50/70 responses, tender joint count (TJC), swollen joint count (SIC), ACR core set components, and low disease activity (LDA) or Disease Activity Score in 28 joints (DAS28) remission. ACR/European League Against Rheumatism (EULAR) disease remission was a posthoc exploratory analysis.Results. Total duration of observation was 12,293 patient-years (PY). No new safety signals were identified; infections were the most common AE and SAE. The rate of serious infections was 4.5/100 PY. Improvements from baseline in clinical efficacy, measured as ACR20/50/70 responses, TIC, SIC, ACR core set components, and LDA and DAS28 remission, were generally sustained through at least 216 weeks of followup. ACR/EULAR disease remission was attained by 16.5% (Boolean) and 22.7% (index) of patients at Week 216.Conclusion. TCZ has to date been studied for up to 4.6 years (240 weeks) of treatment in patients with RA. Our analysis reveals a longer-term safety profile consistent with previous observations, no new safety signals, and durable efficacy of TCZ in a large clinical trial program.