Tahir Hasan, Deodhar Atul, Genovese Mark, Takeuchi Tsutomu, Aelion Jacob, Van den Bosch Filip, Haemmerle Sibylle, Richards Hanno B
Barts Health NHS Trust, London, UK.
Oregon Health and Science University, Portland, OR, USA.
Rheumatol Ther. 2017 Dec;4(2):475-488. doi: 10.1007/s40744-017-0086-y. Epub 2017 Nov 14.
'REASSURE' (NCT01377012), a phase 3 study, evaluated the efficacy and safety of secukinumab in patients with active rheumatoid arthritis (RA) who had an inadequate response to, or intolerance of, tumor necrosis factor inhibitors (TNF-inhibitors).
A total of 637 patients were randomized (1:1:1) to receive intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous secukinumab 150 mg or 75 mg every 4 weeks (starting from week 8) or placebo at the same dosing schedule. The primary endpoint was the American College of Rheumatology 20% improvement criteria (ACR20) at week 24. Other predefined hierarchical endpoints included Health Assessment Questionnaire-Disability Index, van der Heijde modified total Sharp score (vdH-mTSS) at week 24, and major clinical response (MCR; continuous 6 month period of ACR70 response) at 1 year.
The primary efficacy endpoint was met with both secukinumab dose groups: ACR20 response rate at week 24 was 35.2% for both secukinumab dose groups (P = 0.0009) vs 19.6% for placebo. The improvements in secondary endpoints were greater in the secukinumab dose groups vs placebo but did not meet statistical significance. The overall safety profile was similar across all treatment groups.
Secukinumab demonstrated efficacy in reducing disease activity over placebo as measured by ACR20 in patients with active RA who had an inadequate response to TNF-inhibitors. Secukinumab demonstrated a safety profile similar to other biologics currently approved for RA.
Novartis Pharma AG.
ClinicalTrials.gov identifier: NCT01377012.
“REASSURE”（NCT01377012）是一项3期研究，评估了司库奇尤单抗在对肿瘤坏死因子抑制剂（TNF抑制剂）反应不足或不耐受的活动性类风湿关节炎（RA）患者中的疗效和安全性。
总共637例患者按1:1:1随机分组，接受静脉注射司库奇尤单抗10mg/kg（基线、第2周和第4周），随后每4周皮下注射司库奇尤单抗150mg或75mg（从第8周开始），或按相同给药方案给予安慰剂。主要终点是第24周时美国风湿病学会20%改善标准（ACR20）。其他预先定义的分层终点包括健康评估问卷残疾指数、第24周时范德海伊德改良总夏普评分（vdH-mTSS）以及1年时的主要临床反应（MCR；连续6个月达到ACR70反应）。
两个司库奇尤单抗剂量组均达到主要疗效终点：两个司库奇尤单抗剂量组在第24周时的ACR20反应率均为35.2%（P = 0.0009），而安慰剂组为19.6%。与安慰剂组相比，司库奇尤单抗剂量组次要终点的改善更大，但未达到统计学显著性。所有治疗组的总体安全性概况相似。
在对TNF抑制剂反应不足的活动性RA患者中，通过ACR20测量，司库奇尤单抗在降低疾病活动度方面显示出优于安慰剂的疗效。司库奇尤单抗的安全性概况与目前批准用于RA的其他生物制剂相似。
诺华制药股份公司。
ClinicalTrials.gov标识符：NCT01377012。
