Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial.
Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial.
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DOI：
10.1136/annrheumdis-2013-204405
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发表时间：
2014-09
影响因子：
27.4
通讯作者：
Genovese MC
中科院分区：
文献类型：
--
作者：
Huizinga TW;Fleischmann RM;Jasson M;Radin AR;van Adelsberg J;Fiore S;Huang X;Yancopoulos GD;Stahl N;Genovese MC
目的：评价全人型抗白细胞介素6受体α(抗IL-6Rα)单抗沙利鲁单抗治疗中重度类风湿关节炎(RA)的安全性和有效性。在这项剂量范围的研究中，306名活动期RA患者被随机分配到安慰剂或以下5种皮下剂量/方案中的一种：100 mg Q2W、150 mg Q2W、100 mg Q2W、200 mg Q2W、150 mg QW，持续12 周。主要终点为12周时的ACR20。次要终点包括ACR50、ACR70、28个关节的疾病活动评分(C反应蛋白)。在人群亚组中评估安全性、药代动力学、药效学和疗效。与安慰剂相比，服用沙利单抗150 mg qw的患者实现ACR20反应的比例明显更高(72.0%对46.2%，多重性调整后p=0.0203)。与安慰剂相比，服用150 mg Q2W(67%；未调整(标称)p=0.0363)和200 mg Q2W(65%；未调整p=0.0426)的患者也获得了更高的ACR20反应。沙利鲁单抗≥15 0 mg q2w可降低C反应蛋白，但在给药间隔期间C反应蛋白未恢复到基线水平。感染是最常见的不良事件；没有严重的。实验室数值(中性粒细胞减少、转氨酶和血脂)的变化与其他IL-6Rα抑制剂的报告一致。沙利单抗在12 周内改善了中到重度类风湿性关节炎患者的类风湿性关节炎的体征和症状，其安全性与其他IL-6抑制剂的报道相似。沙利单抗150 mg和沙利单抗200 mg Q2W的疗效、安全性和给药方便性最好，正在第三阶段进行进一步评估。
To evaluate safety and efficacy of weekly (qw) and every other week (q2w) dosing of sarilumab, a fully human anti-interleukin 6 receptor α (anti-IL-6Rα) monoclonal antibody, for moderate-to-severe rheumatoid arthritis (RA). In this dose-ranging study, patients (n=306) with active RA, despite methotrexate, were randomly assigned to placebo or one of five subcutaneous doses/regimens of sarilumab: 100 mg q2w, 150 mg q2w, 100 mg qw, 200 mg q2w, 150 mg qw for 12 weeks, plus methotrexate. The primary end point was ACR20 at Week 12. Secondary endpoints included ACR50, ACR70, Disease Activity Score in 28 joints (C reactive protein). Safety, pharmacokinetics, pharmacodynamics and efficacy in population subgroups were assessed. The proportion of patients achieving an ACR20 response compared with placebo was significantly higher for sarilumab 150 mg qw (72.0% vs 46.2%, multiplicity adjusted p=0.0203). Higher ACR20 responses were also attained with 150 mg q2w (67%; unadjusted (nominal) p=0.0363) and 200 mg q2w (65%; unadjusted p=0.0426) versus placebo. Sarilumab ≥150 mg q2w reduced C reactive protein, which did not return to baseline between dosing intervals. Infections were the most common adverse event; none were serious. Changes in laboratory values (neutropenia, transaminases and lipids) were consistent with reports with other IL-6Rα inhibitors. Sarilumab improved signs and symptoms of RA over 12 weeks in patients with moderate-to-severe RA with a safety profile similar to reports with other IL-6 inhibitors. Sarilumab 150 mg and sarilumab 200 mg q2w had the most favourable efficacy, safety and dosing convenience and are being further evaluated in Phase III.
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