Long-term safety and efficacy of sarilumab over 5 years in patients with rheumatoid arthritis refractory to TNF inhibitors
Long-term safety and efficacy of sarilumab over 5 years in patients with rheumatoid arthritis refractory to TNF inhibitors
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DOI：
10.1093/rheumatology/keab355
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发表时间：
2021-04-19
期刊：
影响因子：
5.5
通讯作者：
Burmester, Gerd R.
中科院分区：
文献类型：
--
作者：
Fleischmann, Roy;Genovese, Mark C.;Burmester, Gerd R.
Objective.本研究的目的是评估Sar在TNF抑制剂（TNF i s）难治性RA患者中超过5年的长期安全性和有效性。在为期24周的随机对照试验（RCT）TARGET（NCT 01709578）中，接受双盲安慰剂或sar 150或200 mg每2周一次（q2 w）+常规合成DMARD（csDMARD）的患者有资格在开放标签扩展（OLE）EXTEND（NCT 01146652）中接受开放标签sar 200 mg q2 w + csDMARD。根据研究者的判断或方案规定的安全性问题，允许将OLE剂量降至150 mg q2 w。通过治疗后出现的不良事件（AE）、实验室检查异常和临床DAS评估安全性和疗效。所有的统计数据都是连续的。在546例患者中，454例（83%）在OLE中接受了sar治疗。累积观察期为1654.8患者年（PY; n = 521）; 268例患者（51%）的暴露时间≥ 4年。每100 PY AE、导致停药的AE、感染和严重感染的发生率分别为160.4、8.1、57.8和3.9。中性粒细胞增多症是最常见的AE（15.3/100 PY）。中性粒细胞绝对计数
Objective. The objective of this study was to evaluate the long-term safety and efficacy of sarilumab over 5 years in patients with RA refractory to TNF inhibitors (TNFis).Methods. Patients in the 24-week randomized controlled trial (RCT) TARGET (NCT01709578) who received double-blind placebo or sarilumab 150 or 200mg every 2 weeks (q2w), plus conventional synthetic DMARDs (csDMARDs), were eligible to receive open-label sarilumab 200mg q2w plus csDMARDs in the open-label extension (OLE), EXTEND (NCT01146652). OLE dose reduction to 150mg q2w was permitted per investigators' judgement or protocol-mandated safety concerns. Safety and efficacy were assessed through treatment-emergent adverse events (AEs), laboratory abnormalities and clinical DASs. All statistics are descriptive.Results. Of 546 patients, 454 (83%) were treated with sarilumab in the OLE. The cumulative observation period was 1654.8 patient-years (PY; n = 521); 268 patients (51%) had >= 4 years' exposure. Incidence rates per 100 PY of AEs, and AEs leading to discontinuation, infection and serious infection were 160.4, 8.1, 57.8 and 3.9, respectively. Neutropenia was the most common AE (15.3 per 100 PY). An absolute neutrophil count of