目的:评估sarilumab加/不加常规合成(cs)DMARD治疗RA的长期安全性和有效性。
方法:分析评估了两个开放标签扩展(OLE):EXTEND和MONARCHOLE,其中包括来自6项随机试验的患者.患者接受sarilumab200mg每2周一次(q2w),持续至少264周至516周(扩展:Sarilumab单一疗法和Sarilumab+csDMARD组)或276周(MONARCHOLE:延续和切换组)。主要终点包括安全性,免疫原性和实验室参数的变化。次要终点包括临床体征和症状以及与健康相关的生活质量(HRQOL)问卷。
结果:Sarilumab单一疗法(n=111),继续(n=165)和开关(n=155)组接受sarilumab单药治疗,而Sarilumab+csDMARD组(n=1910)接受sarilumab联合csDMARD。≥1例治疗引起的不良事件(TEAE)的发生率为126(Sarilumab单一疗法组),169(Sarilumab+csDMARD组),159(延续组)和159(转换组)事件/100患者年。中性粒细胞减少症是最常见的AE。中性粒细胞减少症与感染发生率的增加无关。大多数中性粒细胞减少症病例在治疗后恢复正常。特殊利益的不良事件,比如恶性肿瘤,主要不良心血管事件,静脉血栓栓塞和胃肠道穿孔,是罕见的。免疫原性低,并且由于缺乏或失去功效而与超敏反应或中断无关。改善临床体征和症状和HRQOL,在最初的盲法试验中观察到,在整个OLE评估期间保持不变。
结论:在RA患者中使用/不使用csDMARDs的长期sarilumab治疗没有新的安全性发现。在开放标签评估期间,功效和HRQOL得以维持或进一步增加。
背景:扩展,ClinicalTrials.gov,https://www.clinicaltrials.gov/ct2/show/NCT01146652,NCT01146652;MONARCHOLE,ClinicalTrials.gov,https://clinicaltrials.gov/ct2/show/NCT02332590,NCT02332590.
To evaluate the long-term safety and efficacy of sarilumab with/without conventional synthetic (cs)DMARDs in RA.
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.
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.
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.
EXTEND, ClinicalTrials.gov, https://www.clinicaltrials.gov/ct2/show/NCT01146652, NCT01146652; MONARCH OLE, ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02332590, NCT02332590.