Tlustochowicz Witold, Rahman Proton, Seriolo Bruno, Krammer Gerhard, Porter Brian, Widmer Albert, Richards Hanno B
From the Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny, Warsaw, Poland; Memorial University, St. John's, Newfoundland, Canada; Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa, Genoa, Italy; Novartis Pharma AG, Basel, Switzerland; and Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA.W. Tlustochowicz, MD, PhD, Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny; P. Rahman, MD, FRCPC, Memorial University; B. Seriolo, MD, Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa;G. Krammer, MS; A. Widmer, MSc; H.B. Richards, MD, Novartis Pharma AG; B. Porter, MD, PhD, MPH, Novartis Pharmaceutical Corporation.
J Rheumatol. 2016 Mar;43(3):495-503. doi: 10.3899/jrheum.150117. Epub 2016 Feb 1.
To evaluate the efficacy and safety of secukinumab, a fully human antiinterleukin-17A monoclonal antibody, administered with an intravenous (IV) or subcutaneous (SC) loading regimen versus placebo, in patients with active rheumatoid arthritis (RA).
In this phase II, double-blind, double-dummy, 52-week study (ClinicalTrials.gov NCT01359943), 221 patients with inadequate response to methotrexate were randomized (2:2:1) to secukinumab, IV loading 10 mg/kg at baseline, Weeks 2 and 4, then SC 150 mg every 4 weeks (n = 88); secukinumab SC loading 150 mg once weekly for 5 weeks, then every 4 weeks (n = 89); or a matching placebo (followed by secukinumab 150 mg every 4 weeks starting Week 16; n = 44). The primary endpoint was superior efficacy of pooled secukinumab versus placebo using American College of Rheumatology 20% response (ACR20) at Week 12.
The primary efficacy endpoint was not met: ACR20 response at Week 12 was 49.2% for pooled secukinumab versus 40.9% for placebo (p = 0.3559). These variables improved significantly with pooled secukinumab versus placebo at Week 12 (all p < 0.05): the 28-joint Disease Activity Score (DAS28), patient's and physician's global assessment of disease activity, patient's assessment of RA pain, and high-sensitivity C-reactive protein levels. Results of continuous efficacy outcomes were similar between the IV and SC loading regimens. The most frequent adverse events were infections, with similar rates across secukinumab and placebo.
Although the primary endpoint (ACR20) was not met, secukinumab demonstrated improved efficacy in reducing disease activity over placebo as measured by DAS28 and other secondary endpoints.
评估全人源抗白细胞介素-17A单克隆抗体司库奇尤单抗采用静脉注射（IV）或皮下注射（SC）负荷给药方案与安慰剂相比，用于活动性类风湿关节炎（RA）患者的疗效和安全性。
在这项II期、双盲、双模拟、为期52周的研究（ClinicalTrials.gov标识符：NCT01359943）中，221例对甲氨蝶呤反应不足的患者被随机分组（2:2:1），分别接受司库奇尤单抗治疗，静脉注射负荷剂量为基线、第2周和第4周时10mg/kg，之后皮下注射每4周150mg（n = 88）；司库奇尤单抗皮下注射负荷剂量为每周150mg，共5周，之后每4周一次（n = 89）；或匹配的安慰剂（第16周起每4周给予司库奇尤单抗150mg；n = 44）。主要终点是在第12周时，采用美国风湿病学会20%反应率（ACR20）评估，联合使用司库奇尤单抗对比安慰剂的疗效更优。
未达到主要疗效终点：第12周时联合使用司库奇尤单抗的ACR20反应率为49.2%，安慰剂组为40.9%（p = 0.3559）。在第12周时，联合使用司库奇尤单抗对比安慰剂，这些变量有显著改善（所有p < 0.05）：28个关节疾病活动评分（DAS28）、患者和医生对疾病活动的整体评估、患者对类风湿关节炎疼痛的评估以及高敏C反应蛋白水平。静脉注射和皮下注射负荷给药方案的持续疗效结果相似。最常见的不良事件是感染，司库奇尤单抗组和安慰剂组发生率相似。
虽然未达到主要终点（ACR20），但根据DAS28和其他次要终点评估，司库奇尤单抗在降低疾病活动度方面比安慰剂显示出更好的疗效。
