沙利鲁单抗联合或不联合背景 csDMARDs 治疗类风湿关节炎的长期安全性和疗效。
Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis.
机构信息
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin, Berlin, Germany.
Division of Immunology/Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA.
出版信息
Rheumatology (Oxford). 2023 Oct 3;62(10):3268-3279. doi: 10.1093/rheumatology/kead062.
OBJECTIVE
To evaluate the long-term safety and efficacy of sarilumab with/without conventional synthetic (cs)DMARDs in RA.
METHODS
The analyses evaluated two open-label extensions (OLEs): EXTEND and MONARCH OLE, which included patients from six randomized trials. Patients received sarilumab 200 mg once every 2 weeks (q2w) for at least 264 weeks up to 516 weeks (EXTEND: Sarilumab Monotherapy and Sarilumab + csDMARD groups) or for 276 weeks (MONARCH OLE: Continuation and Switch groups). Primary endpoints included safety, immunogenicity and changes in laboratory parameters. Secondary endpoints included clinical signs and symptoms along with health-related quality-of-life (HRQOL) questionnaires.
RESULTS
The Sarilumab Monotherapy (n = 111), Continuation (n = 165) and Switch (n = 155) groups received sarilumab monotherapy, while the Sarilumab + csDMARD group (n = 1910) received sarilumab in combination with csDMARDs. Incidence of one or more treatment-emergent adverse events was 126 (Sarilumab Monotherapy group), 169 (Sarilumab + csDMARD group), 159 (Continuation group) and 159 (Switch group) events/100 patient-years. Neutropenia was the most common adverse event. Neutropenia was not associated with an increased incidence of infections. Most neutropenia cases normalized on-treatment. Adverse events of special interests, such as malignancies, major adverse cardiovascular events, venous thromboembolism and gastrointestinal perforations, were rare. Immunogenicity was low and not associated with hypersensitivity reactions or discontinuations due to lack or loss of efficacy. Improvements in clinical signs and symptoms and HRQOL, observed during the initial blinded trials, were maintained throughout the OLE assessment period.
CONCLUSIONS
Long-term sarilumab treatment with/without csDMARDs in patients with RA revealed no new safety findings. Efficacy and HRQOL were maintained or further increased over the open-label assessment period.
TRIAL REGISTRATION
EXTEND, ClinicalTrials.gov, https://www.clinicaltrials.gov/ct2/show/NCT01146652, NCT01146652; MONARCH OLE, ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02332590, NCT02332590.
目的
评估 sarilumab 联合/不联合常规合成（cs）疾病修饰抗风湿药物（DMARDs）治疗类风湿关节炎（RA）的长期安全性和疗效。
方法
分析包括两项开放标签扩展（OLE）研究：EXTEND 和 MONARCH OLE，入组了来自六项随机对照试验的患者。患者接受 sarilumab 200mg，每 2 周（q2w）1 次，至少 264 周，最长达 516 周（EXTEND：sarilumab 单药治疗和 sarilumab + csDMARD 组）或 276 周（MONARCH OLE：继续治疗和转换组）。主要终点包括安全性、免疫原性和实验室参数变化。次要终点包括临床症状和体征以及健康相关生活质量（HRQOL）问卷。
结果
Sarilumab 单药治疗组（n=111）、继续治疗组（n=165）和转换组（n=155）接受 sarilumab 单药治疗，而 sarilumab + csDMARD 组（n=1910）接受 sarilumab 联合 csDMARDs 治疗。100 患者-年中发生 1 次或多次治疗期不良事件的患者数分别为 126 例（sarilumab 单药治疗组）、169 例（sarilumab + csDMARD 组）、159 例（继续治疗组）和 159 例（转换组）。最常见的不良事件为中性粒细胞减少。中性粒细胞减少与感染发生率增加无关。大多数中性粒细胞减少病例在治疗过程中恢复正常。特殊关注的不良事件，如恶性肿瘤、主要不良心血管事件、静脉血栓栓塞和胃肠道穿孔，较为罕见。免疫原性较低，与过敏反应或因缺乏或丧失疗效而停药无关。在初始双盲试验中观察到的临床症状和体征以及 HRQOL 的改善，在 OLE 评估期间得以维持。
结论
在 RA 患者中，联合或不联合 csDMARDs 进行长期 sarilumab 治疗未发现新的安全性问题。疗效和 HRQOL 在开放标签评估期间得以维持或进一步提高。
试验注册
EXTEND，ClinicalTrials.gov，https://www.clinicaltrials.gov/ct2/show/NCT01146652，NCT01146652；MONARCH OLE，ClinicalTrials.gov，https://clinicaltrials.gov/ct2/show/NCT02332590，NCT02332590。
Zotero 插件